TreatmentRecommendations forAdult InpatientsAlso available online at:www.insidehopkinsmedicine.org/ampantibioticguidelines2009-20101. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3stn2. Johns Hopkins Hospital formulary and restriction status . . . . .6et2.1 Obtaining IDapproval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7no2.2 Formulary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8c fo 3. Agent-specific guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . .9e3.1Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9blAmpicillin/sulbactam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9TaColistin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9Daptomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10Ertapenem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10Fosfomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11Linezolid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12Rifaximin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13Tigecycline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13Vancomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143.2Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16AmBisome® . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16Micafungin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17Posaconazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18Voriconazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .204. Microbiology information . . . . . . . . . . . . . . . . . . . . . . . . . . . . .234.1Interpreting the microbiology report . . . . . . . . . . . . . . . . . . . .234.2 Johns Hopkins Hospital antibiogram . . . . . . . . . . . . . . . . . . . .245. Guidelines for the treatment of various infections . . . . . . . . .275.1 Abdominal infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27Biliary tract infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27Diverticulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29Peritonitis (including SBP, GI perforation and peritonitis related to peritoneal dialysis) . . . . . . . . . . . . . . . . . . . . . . . . .315.2 Clostriduim difficileinfection (CDI) . . . . . . . . . . . . . . . . . .355.3 Infectious diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . .385.4 H. pylori infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .415.5 Catheter-associated bloodstream infections . . . . . . . . .435.6 Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .475.7 Central nervous system (CNS) infections . . . . . . . . . . . .53Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .53Encephalitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55Brain abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56CNSshunt infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .56Antimicrobial doses for CNS infections . . . . . . . . . . . . . . . . .575.8 Gynecologic infections . . . . . . . . . . . . . . . . . . . . . . . . . . .58PID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .58Endomyometritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .59Uncomplicated gonococcal urethritis, cervicitis, proctitis . . . .59Septic pelvic thrombophlebitis . . . . . . . . . . . . . . . . . . . . . . .60(continued on next page)1stn5.9Pulmonary infections . . . . . . . . . . . . . . . . . . . . . . . . . . .61etCOPD exacerbations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61noCommunity-acquired pneumonia . . . . . . . . . . . . . . . . . . . . .62c fHealthcare-acquired pneumonia. . . . . . . . . . . . . . . . . . . . . .65o eVentilator-associated pneumonia . . . . . . . . . . . . . . . . . . . . .66blCystic fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .69Ta5.10 Influenza . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .715.11 Tuberculosis (TB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .735.12 Sepsis in the ICU patient with no clear source . . . . . .775.13 Skin and soft-tissue infections . . . . . . . . . . . . . . . . . .79Cellulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79Management of skin and skin-structure infections due to MRSA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .81Diabetic foot infections . . . . . . . . . . . . . . . . . . . . . . . . . .82Surgical-site infections . . . . . . . . . . . . . . . . . . . . . . . . . . .84Serious, deep soft-tissue infections (necrotizing fasciitis) . .865.14 Urinary tract infections(UTI) . . . . . . . . . . . . . . . . . . . .89Bacterial UTI (including pyelonephritis and urosepsis) . . . .895.15 Resistant Gram-negative infections . . . . . . . . . . . . . .935.16 Candidiasis in the non-neutropenic patient . . . . . . . .975.17 Guidelines for the use of prophylactic antimicrobials . .103Fluconazole prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . .103Pre-operative and pre-procedure antibiotic prophylaxis . .104Prophylaxis against bacterial endocarditis . . . . . . . . . . .108Prophylactic antimicrobials for patients with solid organ transplants . . . . . . . . . . . . . . . . . . . . . . . . .1095.18 Guidelines for the use of antimicrobials inneutropenic hosts. . . . . . . . . . . . . . . . . . . . . . . . . . . .111Treatment of neutropenic fever . . . . . . . . . . . . . . . . . . .111Prophylactic antimicrobials in neutropenic patients . . . . .113Use of antifungal agents in hematologic malignancy patients .1146. Informational guidelines . . . . . . . . . . . . . . . . . . . . . . . . .1186.1 Approach to the patient with a history of penicillin allergy . .1186.2 Combination therapy or “double coverage” of Gram-negative infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1207. Infection control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1227.1 Hospital Epidemiology & Infection Control . . . . . . . . . . . .1227.2 Infection control precautions . . . . . . . . . . . . . . . . . . . . .1247.3 Disease-specific infection control recommendations . . . .1268. Bioterrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1309. Appendix:A. Aminoglycoside dosing and therapeutic monitoring . . . . . .132B. Vancomycin dosing and therapeutic monitoring . . . . . . . .138C. Antimicrobial therapy monitoring . . . . . . . . . . . . . . . . . . .140D. Oral antimicrobial use . . . . . . . . . . . . . . . . . . . . . . . . . . .141E. Antimicrobial dosing in renal failure . . . . . . . . . . . . . . . . . .142F. Cost of select antimicrobial agents . . . . . . . . . . . . . . . . . .14610. Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1492IntroductionnoticuAntibiotic resistance is now a major issue confronting healthcareodproviders and their patients. Changing antibiotic resistance patterns,trnrising antibiotic costs and the introduction of new antibiotics have I.1made selecting optimal antibiotic regimens more difficult now than everbefore. Furthermore, history has taught us that if we do not useantibiotics carefully, they will lose their efficacy. As a response to thesechallenges, the Johns Hopkins Antibiotic Management Program wascreated in July 2001. Headed by an Infectious Disease physician (SaraCosgrove, M.D., M.S.) and an Infectious Disease pharmacist (EdinaAvdic, Pharm.D., M.B.A), the mission of the program is to ensure thatevery patient at Hopkins on antibiotics gets optimal therapy. Theseguidelines are a step in that direction. The guidelines were initiallydeveloped by Arjun Srinivasan, M.D., and Alpa Patel, Pharm.D., in2002 and have been revised and expanded annually.These guidelines are based on current literature reviews, includingnational guidelines and consensus statements, current microbiologicdata from the Hopkins lab, and Hopkins’ faculty expert opinion. Facultyfrom various departments have reviewed and approved theseguidelines. As you will see, in addition to antibiotic recommendations,the guidelines also contain information about diagnosis and otheruseful management tips.As the name implies, these are only guidelines, and we anticipate thatoccasionally, departures from them will be necessary. When these casesarise, we will be interested in knowing why the departure is necessary.We want to learn about new approaches and new data as they becomeavailable so that we may update the guidelines as needed. You shouldalso document the reasons for the departure in the patient’s chart.Finally, please let us know if there are sections that you think could beimproved, and also let us know if there is more information you wouldlike to see included. Our goal is for the Antibiotic ManagementProgram to be a useful service in optimizing antibiotic use at Hopkins.We welcome your thoughts and comments to 443-287-4570 (7-4570)or to: abxmgmt@jhmi.edu.Sara E. Cosgrove, M.D., M.S.Director, Antibiotic Management ProgramEdina Avdic, Pharm.D., M.B.AID PharmacistAssociate Director, Antibiotic Management Program3noAcknowledgementsticThese guidelines were a team effort. We wish to thank everyone who helpedureview the document.odtrnThe following people reviewed allthe treatment guidelines I.Jane Abrams, Pharm.D. (Pharmacy)1Paul Auwaerter, M.D. (Infectious Diseases)John Bartlett, M.D. (Infectious Diseases)Karen Carroll, M.D. (Pathology/Infectious Diseases)Patricia Charache, M.D., Ph.D. (Infectious Diseases and Pathology)Pam Lipsett, M.D. (Surgery and Critical Care)Eric Nuermberger, M.D. (Infectious Diseases)Trish Perl, M.D., M.Sc. (Infectious Diseases)Stuart Ray, M.D. (Infectious Diseases)Annette Rowden, Pharm.D. (Pharmacy)Cynthia Sears, M.D. (Infectious Diseases)The following people served as section/topic reviewersN. Franklin Adkinson, M.D. (Allergy/Immunology)Carolyn Alonso, M.D. (Infectious Diseases)Rebecca Aslakson, M.D. (Critical Care)Michael Boyle, M.D. (Pulmonary)Robert Brodsky, M.D. (Oncology)Roy Brower, M.D. (Critical Care and Pulmonary)Daniel Chertow, M.D. (Infectious Diseases)Michael Choi, M.D. (Nephrology)John Clarke, M.D. (Gastroenterology)Amanda Colquitt, Pharm.D. (Pharmacy)Todd Dorman, M.D. (Critical Care)Emily Erbelding, M.D. (Infectious Diseases)Oluwaseun Falade, M.D. (Infectious Diseases)Nauder Faraday, M.D. (Critical Care)Francis Giardiello, M.D. (Gastroenterology)Celine Gounder, M.D. (Infectious Diseases)Alice Jenh, Pharm.D. (Pharmacy)Judith Karp, M.D. (Oncology)Rahul Kohli, M.D. (Infectious Diseases)Lisa Maragakis, M.D. (Infectious Diseases)Kieren Marr, M.D. (Infectious Diseases)Dennis Neofytos, M.D. (Infectious Diseases)Catherine Passaretti, M.D. (Infectious Diseases)Paul Pham, Pharm.D. (Infectious Diseases)Anne Rompalo, M.D. (Infectious Diseases)Paul Scheel, M.D. (Nephrology)Amy Seung, Pharm.D. (Pharmacy)Maunank Shah, M.D. (Infectious Diseases)Aruna Subramanian, M.D. (Infectious Diseases)Ryan Westergaard, M.D. (Infectious Diseases)Robert Wise, M.D. (Pulmonary)Frank Witter, M.D. (OB-GYN)4How to use this guideno• Each section begins by giving recommendations for the choice andticdose of antibiotics for the particular infection. u• ALL DOSES IN THE TEXT ARE FOR ADULTS WITH NORMALodtrRENAL AND HEPATIC FUNCTION.n I.• If your patient does NOT have normal renal or hepatic function,1please refer to the sections on antibiotic dosing to determine thecorrect dose.• Following the antibiotic recommendations, we have tried to includesome important treatment notes that explain a bit about WHY theparticular antibiotics were chosen and that provide some important tipson diagnosis and management. PLEASE glance at these notes whenyou are treating infections, as we think the information will provehelpful. All references are on file in the office of the AntibioticManagement Program (7-4570).Important phone numbers • Antibiotic approval: 3-9ABX (3-9229)• Please note that text pages alone are NOT sufficient and MUSTinclude a call-back phone and pager number.• ALL orders for restricted antibiotics MUST be approved unless theyare part of a pre-printed order sheet. • Please see page 7 for more information about obtaining approval.• Antibiotic Management Program: 7-4570• Infectious Diseases Consults: 3-8026• Osler 2 pharmacy: 5-6150• Carnegie 6 pharmacy: 5-6505• Weinberg pharmacy: 5-8998• Microbiology lab: 5-6510A word from our lawyersThe recommendations given in this guide are meant to serve astreatment guidelines. They should NOT supplant clinical judgment orInfectious Diseases consultation when indicated. The recommendationswere developed for use at The Johns Hopkins Hospital and thus may notbe appropriate for other settings. We have attempted to verify that allinformation is correct but because of ongoing research, things maychange. If there is any doubt, please verify the information in the guideby calling the antibiotics pager (3-9ABX) or Infectious Diseases (3-8026).Also, please note that these guidelines contain cost informationthat is confidential. Copies of the book should notbe distributedoutside of the institution without permission.5alvoAdult Inpatient Antibiotic Approval Form Abdominal Infectionsappr■D■1aBiliary tract infection – community-acquired, mild/mod. ill I■ ngni■ 1bBiliary tract infection – severely ill and/or nosocomial■ 2a2bDiverticulitis – community-acquired, mild/mod. ill Diverticulitis – severely ill and/or nosocomial aitOb■ 3aPeritonitis – community-acquired, mild/mod. ill 1■ .2■ 3bPeritonitis – severely ill and/or nosocomial 45aCrohn’s disease – stable patient admitted on daily oral ciprofloxacinSpontaneous Bacterial Peritonitis (SBP), treatment Central Nervous System Infections■■ 7a7bMeningitis – community-acquired Meningitis – hospital-acquired/post-operative Skin And Soft Tissue Infections■■ 9Cellulitis■ 10Diabetic foot infection – mild ■ ■ 10a10bDiabetic foot infection – moderate ■ 11aDiabetic foot infection – severe 11bSurgical site infection – following clean procedure Surgical site infection – following contaminated procedure Pneumonias■■ 13Community-acquired pneumonia – infiltrate required ■ 13b14Hospital-acquired pneumonia – infiltrate required Ventilator associated pneumonia – infiltrate required Urinary Tract Infections- note criteria in guidelines■■ ■ 15 16Cystitis – bacterial – symptomatic; Bactrim preferred 17Pyelonephritis Cystitis – fungal Fluconazole■■ 18aHIV positive, esophageal candidiasis■ 18bMedical oncology patient, esophageal candidiasis■ 1920HIV positive, admitted on daily fluconazoleLiver/pancreas transplant, admitted on daily fluconazoleVancomycin■■ 2122≥Severe PCN allergy & infection with MSSA or Enterococcus – culture from2 sets of blood cultures with Gram (+) cocci in clustersa sterile site or abscess within prior 72 h. required■ 23aProven infection with MRSA – culture from a sterile site or abscess withinprior 72 h. required■ 23bProven infection with Ampicillin-resistant Enterococcus – culture from asterile site or abscess within prior 72 h. required■ 24PCN allergy in patient needing prophylaxis for cardiac, vascular, ororthopedic (joint replacement, spinal fusion, ORIF only) surgery (NO morethan one pre-op and one post-op dose)6Obtaining ID approvalalvorThe use of restricted and non-formulary antimicrobials requires pre-appapproval from Infectious Diseases. This approval can be obtained by anyof the following methods. IDngniApproval methodNotesaitAdult Inpatient This form allows the use of specific Ob Antibiotic Approval Formagents for specific indications. For1.2therapies not recommended on thereverse side of the form, approval shouldbe obtained via the pager. Please notethat it is NOT an order form andMUST be accompanied by an order. 3-9ABX (3-9229)The pager is answered between 8 a.m.and 10 p.m. Call the ID consult pager (3-8026) if you fail to get a response fromthe ID approval pager within 10 minutes.Overnight ApprovalRestricted antibiotics ordered between10 p.m. and 8 a.m. must be approved bynoon the following morning.• Doses will be dispensed to last untilnoon• Methods to obtain approval• Antibiotic Approval Form (see above)• Page ID approval (3-9229) after 8 a.m.• Please remember to sign out the needfor approval if you go off shift before 8 a.m.Liposomal Amphotericin BThis form should be completed for allApproval Form patients meeting criteria for AmBisome®.For circumstances not delineated on theform, approval for AmBisome®can beobtained via the pager, or afterconsultation with ID.Ordersets (e.g. neutropenicThese forms are P&T-approved forfever, etc.)specific agents and specific indications.7sutSelected formulary antimicrobials ats and restriction statusnoticThe following list applies to ALL adult floors and includes the status oftriseboth oral and injectable dosage forms, unless otherwise noted. rndUnrestrictedRestricted (requires IDaapproval) yAmoxicillinMinocyclineAmikacinarNitrofurantoinAmpicillin/sulbactamulAmoxicillin/mclavulanateNorfloxacin(Unasyn®)orAmpicillin IVOxacillinAzithromycin IV1f Azithromycin POPenicillin V/GAztreonamalCefazolinPiperacillinCefepimeobiCefotetanRifampinCeftazidimecrCefoxitinStreptomycinChloramphenicolmiCefpodoximeTobramycinCiprofloxacintinCeftriaxoneTrimethoprim/Colistin IV ACefuroxime IVsulfamethoxazoleDaptomycin* 2.CephalexinFosfomycin2ClarithromycinLinezolidClindamycin (IV dose: 600Meropenemmg every 8H)MoxifloxacinDicloxacillinNitazoxanide‡DoxycyclinePiperacillin/tazobactamErtapenem(Zosyn®)ErythromycinQuinupristin/Gentamicindalfopristin (Synercid®)MetronidazoleTigecyclineVancomycinAmphotericin BLiposomal amphotericin Bdeoxycholate(AmBisome®)2(Fungizone®)MicafunginFlucytosineFluconazole3Itraconazole oral solutionPosaconazole†Voriconazole*Approval should be obtained from Antibiotic Management Program†Approval should be obtained from Antibiotic Management Program, Polk ServiceFellow/Attending, or ID consult service after full consultation‡Approval should be obtained from Polk Service or ID ConsultExceptions – the following drugs DO NOT require ID approval under specific conditions:1. Azithromycin IV, when used as a single dose for chlamydial infection, when used weekly forMAI prophylaxis, or when ordered Monday, Wednesday, and Friday as a continuation ofoutpatient therapy in lung transplant or cystic fibrosis patients.2. Liposomal amphotericin B (AmBisome), if criteria on the AmBisome®Form are met andform is submitted to pharmacy.3. Oral Fluconazole, when used as a single-dose treatment for vulvovaginal candidiasis orwhen used in compliance with the SICU/WICU protocol.Restricted antimicrobials that are ordered as part of a P&T-approved critical pathway ororder set do NOT require ID approval.REMINDER: the use of non-formulary antimicrobials is strongly discouraged. IDapproval MUSTbe obtained for ALLnon-formulary antimicrobials.NOTE: Formulary antivirals (e.g. Acyclovir, Ganciclovir) do NOT require ID approval.8AntibioticssctioAmpicillin/sulbactam (Unasyn®)bitinA Ampicillin/sulbactam is a beta-lactam/beta-lactamase inhibitor:secombination antibiotic. It has activity against MSSA, streptococci,nentercocci, and anaerobes. Its activity against Gram-negative organismseliis limited; an increasing number of E. coliand Proteusisolates are nowuid gresistant. cfiAcceptable usescie• Treatment of human or animal bites if IV therapy is neededspt-• Treatment of oral infectionsne• Treatment of lung abscessAg • Treatment of culture negative endocarditis1.3Unacceptable uses• Empiric treatment of biliary tract infections, diverticulitis, orsecondary/peritonitis/GI perforation (use can be considered only ininfections with organisms that are proven to be susceptible)Dose • 1.5-3 g IV Q6H• 3 g IV Q4H for multi-drug resistant Acinetobacter(see p. 93)Colistin (Colistimethate) Colistin is a polymixin antibiotic. It has invitroactivity againstAcinetobacter spp.and Pseudomonas spp.but does NOT have activityagainst Proteus, Serratia, Providentia, Burkholderia, Gram-negativecocci, Gram-positive organisms, or anaerobes. Acceptable uses• Management of infections due to multi-drug resistant Acinetobacterand Pseudomonason a case by case basis. Unacceptable uses • Monotherapy for empiric treatment of suspected Gram-negativeinfections Dose• 5 mg/kg/day divided in 2 doses, must adjust for worsening renalfunction and dialysis (see p. 142 for dose adjustmentrecommendation). Toxicity• Renal impairment, neuromuscular blockade, neurotoxicity• Monitoring: BUN, creatinine twice-weekly9sctiDaptomycin otibiDaptomycin is a lipopeptide antibiotic. It has activity against most strainsnAof staphylococci and streptococci (including MRSA and VRE). It does :seNOT have activity against Gram-negative organisms. nielAcceptable uses(Cases must be discussed with Infectious Diseasesuidand Antibiotic Management Program) gc• Bacteremia or endocarditis caused by MRSA or Methicillin-resistantficicoagulase-negative staphylococci in a patient with serious allergy toeVancomycinspt-• Therapy for MRSA infections other than pneumonia in which the MIC ofneVancomycin is > 2 mcg/mLAg • Bacteremia or endocarditis caused by MRSA in a patient failing1.3Vancomycin therapy as defined by: • Clinical decompensation after 3–4 days• Failure to clear blood cultures after 7–9 days despite Vancomycintroughs of 15–20 mcg/mL• Select cases in which the MIC of Vancomycin is 2 mcg/mL• Salvage therapy for VRE infections other than pneumonia, on a case bycase basisUnacceptable uses• Daptomycin should NOT be used for treatment of pneumonia due to itsinactivation by pulmonary surfactant. • Initial therapy for Gram-positive infections • VRE colonization of the urine, respiratory tract, wounds, or drains Dose• Bacteremia: 6–12 mg/kg IV Q 24H• Endocarditis: 6–12 mg/kg IV Q 24H• Dose adjustment is necessary for CrCl < 30 ml/min (see p. 142 fordose adjustment recommendation). Toxicity• Myopathy (defined as CK ≥10 times the upper limit of normal withoutsymptoms or ≥5 times the upper limit of normal with symptoms).• Monitoring: CK weekly, more frequently during initial therapy. References: Daptomycin in S. aureusbacteremia and infective endocarditis: N Engl J Med 2006; 355:653–65.ErtapenemErtapenem is a carbapenem antibiotic. It has in vitroactivity againstmany Gram-negative organisms including those that produce extendedspectrum beta-lactamases (ESBL), but it does not have activity against10Pseudomonas spp. or Acinetobacter spp.Its anaerobic and Gram-scpositive activity is similar to that of other carbapenems, except it doestionot have activity against Enteroccocus spp. bitinAcceptable usesA :• Mild to moderate intra-abdominal infections (biliary tract infections,sediverticulitis, secondary peritonitis/GI perforation) neli• Moderate diabetic foot infections without osteomyelitisdui• Moderate surgical-site infections following contaminated procedure g• Urinary tract infections caused by ESBL-producing organisms cfi• Pyelonephritis in a patient who is not severely illcieUnacceptable usesspt-• Severe infections in whichPseudomonas spp. are suspected. neDoseAg 1• 1 g IV or IM Q24H, must adjust for worsening renal function and.3dialysis (seep. 142 for dose adjustment recommendation)Toxicity• Diarrhea, nausea, headache, phlebitis/thrombophlebitisFosfomycin Fosfomycin is a synthetic, broad-spectrum, bactericidal antibiotic with invitroactivity against large number of gram-negative and gram-positiveorganisms including E. coli, Klebsiella spp.,Proteus spp. Pseudomonasspp.,and VRE. It does not have activity against Acinetobacter spp.Fosfomycin is available in an oral formulation only in the U.S. and itspharmacokinetics allow for one-time dosing.Acceptable uses• Management of uncomplicated UTI in patients with multiple antibioticallergies and when oral therapy is indicated.• Uncomplicated UTI due to VRE• Salvage therapy for UTI due to multi-drug resistant Gram-negativeorganisms (e.g.Pseudomonas spp.) on case by case basis. NOTE:Susceptibility to Fosfomycin should be confirmed prior toinitiation of therapy. Unacceptable uses• Fosfomycin should NOT be used for management of any infectionsoutside of the urinary tract because it does not achieve adequateconcentrations at other sites.Dose• Uncomplicated UTI: 3 g (1 sachet) PO once. • Complicated UTI: 3 g (1 sachet) PO every 2-3 days (up to 21 days oftreatment) 11sc• Frequency adjustment may be necessary in patients with CrCl <50tiomL/min. Contact the Antibiotic Management Program for dosingtibirecommendations. nA • Powder should be mixed with 90–120 mL of cool water, stirred to:sedissolve and administered immediately. nielToxicity uid• Diarrhea, nausea, headache, dizziness, asthenia and dyspepsia gcficiLinezolidespAcceptable usest-ne• Documented Vancomycin intermediate Staphylococcus aureus(VISA)Agor Vancomycin resistant Staphylococcus aureus(VRSA) infection 1.• Documented MRSA or Methicillin-resistant coagulase-negative3staphylococcal infection in a patient with serious allergy to Vancomycin• Documented MRSA or Methicillin-resistant coagulase-negativestaphylococcal infection in a patient failing Vancomycin therapy (asdefined below): • Bacteremia/endocarditis: failure to clear blood cultures after 7–9days despite Vancomycin troughs of 15–20 mcg/mL. Shouldbe used in combination with another agent• Pneumonia: worsening infiltrate or pulmonary status in a patientwith documented MRSA pneumonia after 2 to 3 days or if the MICof Vancomycin is 2 mcg/mL.Cases should be discussed with Infectious Diseases or AntibioticManagement.• High suspicion of CA-MRSA necrotizing pneumonia in a seriously ill patient• Documented VRE infection • Gram-positive cocci in chains in blood cultures in an ICU, or oncologytransplant patient known to be colonized with VREUnacceptable uses• Prophylaxis• Initial therapy for staphylococcal infection• VRE colonization of the stool, urine, respiratory tract, wounds, or drainsDose• 600 mg IV/PO Q12H• Skin and skin-structure infections: 400 mg IV/PO Q12HToxicity• Bone marrow suppression (usually occurs within first 2 weeks oftherapy)• Optic neuritis and irreversible sensory motor polyneuropathy (usuallyoccurs with prolonged therapy > 28 days)12• Case reports of lactic acidosissc• Case reports of serotonin syndrome when co-administered withtioiserotonergic agents (SSRIs, TCAs, MAOIs, etc.)tib• Monitoring: CBC weeklynA :sRifaximineneliRifaximin is a nonabsorbable, semi-synthetic antibiotic derived fromuidrifamycin that is FDA approved for treatment of travelers’ diarrhea gccaused by noninvasive strains of E. coli. It may be used as an alternativeficito lactulose for hepatic encephalopathy (HE) in patients meeting theecriteria below. It is not on the formulary at JHH and requires ID approval.spt-nAcceptable useseAgHepatic encephalopathy in patients meeting the following criteria: 1.• Refractory to lactulose: patient continues to experience HE symptoms3despite receiving lactulose at a dose that obtains 2–3 loose stoolsperday. • Intolerance to lactulose: patient requiring maintenance therapy with ≥4 loose stools per day despite dosage reductions. Dose• 200–800 mg PO Q8HToxicity • Diarrhea, abdominal pain, headache. Rare hypersensitivity reactions(dermatitis, rash, angioneurotic edema, urticaria, and pruritis) havebeen reported in post-marketing trials. TigecyclineTigecycline is a tetracycline derivative called a glycylcycline. It has invitroactivity against most strains of staphylococci and streptococci(including MRSA and VRE), anaerobes, and many Gram-negativeorganisms with the exception of Proteus spp. and Pseudomonasaeruginosa. It is FDA approved for skin and skin-structure infections andintra-abdominal infections. NOTE:Peak serum concentrations of Tigecycline do not exceed 1 mcg/mL which limits its use for treatment of bacteremiaAcceptable uses• Management of intra-abdominal infections in patients withcontraindications to both beta-lactams and fluoroquinolones• Management of infections due to multi-drug resistant Gram-negativeorganisms including Acinetobacter spp. and Stenotrophomonasmaltophiliaon a case by case basis• Salvage therapy for MRSA/VRE infections on a case by case basis13scDosetio• 100 mg IV once, then 50 mg IV Q12Htibi• 100 mg IV once, then 35 mg IV Q12H if severe hepatic impairmentnA (Child - Pugh 10–15):senToxicityiel• Nausea and vomiting uid gcVancomycinficieAt The Johns Hopkins Hospital in 2008, 58% of S. aureusisolates inspt-adult patients were resistant to Oxacillin. These data suggest thatneempiric use of Vancomycin is advisable for an ill patient with suspectedAgS. aureusinfection. However, Vancomycin should be stopped if culture 1.3data do not indicate a need for continued definitive therapy (see below).Limiting prolonged or inappropriate use of Vancomycin isessential.There are few instances when continued use of Vancomycin isappropriate in the absence of positive cultures. The following arerecommendations for empiric, definitive, and prophylactic Vancomycinuse:Acceptable empiric useNOTE:therapy should be discontinued within 72 hours if criteria fordefinitive therapy (see below) are not met:• Treatment of suspected community- or nosocomially acquired bacterialmeningitis • Treatment of ventilator-associated pneumonia• Treatment of peritoneal dialysis-related peritonitis in a severely ill patient• Treatment of sepsis in a patient at risk for MRSA bacteremia [catheterin place, indwelling hardware, known colonization with MRSA, transferfrom a nursing home or subacute facility, recent (within 3 months) orcurrent prolonged hospitalization > 2 weeks]• Treatment of surgical-site infection following placement of hardware• Treatment of severe diabetic foot infection in a patient at risk for MRSA• Treatment of necrotizing fasciitis• Treatment of suspected endocarditis in a moderately or severely illpatient after appropriate blood cultures are obtained (injection-drugusers with low-grade fevers and no clinical evidence of endocarditis orsepsis should NOT receive empiric Vancomycin)• Treatment of Gram-positive cocci in clusters in ≥1 set of bloodcultures in a moderately or severely ill patient• Treatment of Gram-positive cocci in clusters or chains in ≥2 sets ofblood cultures in any patient14sAcceptable use for definitive INTRAVENOUS therapyctio• Proven infection with beta-lactam resistant organismstibi• MRSAnA • Methicillin-resistant coagulase-negative staphylococcus :se• Ampicillin-resistant enterococcus (if Vancomycin susceptible)n• Ceftriaxone-resistant S. pneumoniae(CSF only)elidui• Treatment of infections caused by Gram-positive organisms in patients gwho have serious allergies to beta-lactam agents (see p. 118 forcfidiscussion of penicillin allergy)ciespt-Acceptable use for definitive ORAL therapyne• Clostridium difficileinfection (see CDI section, p. 35)Ag 1.3Acceptable use for prophylaxis• Prophylaxis for cardiac, vascular or orthopedic (joint replacement,spinal fusion, ORIF ONLY) surgery in patients with severe PCN allergy(no more than one pre-op and one post-op dose)Unacceptable uses for Vancomycin• Continued empiric use for presumed infection with negative cultures• Treatment of a single-positive blood culture for coagulase-negativestaphylococci• Routine surgical prophylaxis• Empiric treatment for first fever in neutropenic patients withoutevidence of catheter-related bloodstream infection, severe mucositis,or history of MRSA• Prophylaxis for infection or colonization of indwelling intravascularcatheters• Selective decontamination of the digestive tract• Eradication of MRSA colonization• Routine prophylaxis for patients on continuous ambulatory peritonealdialysis or hemodialysis• Treatment (chosen for dosing convenience) of infections caused bybeta-lactam sensitive organisms in patients who have renal failure• Use of Vancomycin solution for topical application or irrigation15salAntifungalsnguftinDefinitionsA :Definiteinvasive aspergillosis is established by positive culture orsehistopathology for aspergillosis from tissue obtained during anneliinvasive procedure. Washings, brushings, or suctioning of secretionsdo NOT represent invasive procedures.uidProbableaspergillosis is indicated by a positive galactomannan assay from gcserum or BAL or positive culture for aspergillus species AND clinicalficievidence suggestive of aspergillosis. ePossibleaspergillosis is indicated by a positive galactomannan assay fromspserum or BAL or radiographic findings highly suggestive oft-neaspergillosis in a compatible host (follow-up diagnostic studies arehighly recommended).Ag 2Refractorymeans disease progression or failure to improve despite at least 96.3hours of treatment with Voriconazole or an IV Amphotericin B product(deoxycholate or lipid-based product).Liposomal Amphotericin B (AmBisome®)Patients must meet one or more of the criteria below to receiveAmBisome®unless otherwise approved by ID 1. Patients currently experiencing or with history of toxicity related toconventional Amphotericin B administration• Infusional toxicity (defined as 2 episodes of rigors despitepremedication with diphenhydramine, acetaminophen, and eitherhydrocortisone or dexamethasone)• Acute renal failure (defined as doubling of serum creatinine frombaseline or urine output < 0.5 mL/kg/hour for > 2 hours despiteadequate fluid resuscitation)2. Patients with renal disease–NOT ESRD ON DIALYSIS• Estimated or collected CrCl ≤40 mL/min• Acute renal failure (doubling of serum creatinine from baseline orurine output < 0.5 mL/kg/hour for > 2 hours despite adequatefluid resuscitation)• Renal transplant, single kidney, lupus nephritis3. Patients at risk for renal failure • Age ≥65• ICU patient with sepsis• End-stage liver disease• Multiple myeloma/amyloidosis• Active tumor lysis syndrome16• Allogeneic BMT/HSCT until hematopoietic recovery andsdiscontinuation of immune suppressionalng• Patient receiving or about to receive cytarabine (ARA-C) withinuf48hourstinA• Concurrent nephrotoxic therapy :sAminoglycosides, Colistin, Foscarnet, Cidofovir, Cyclosporine,eniTacrolimus, Carboplatin, Cisplatin, high-dose Methotrexateeld(>1000 mg/m2/dose)ui g4. Patients receiving long-course, high-dose therapy with Amphotericin B,cfidefined as ≥ 2 weekscie• Definite or probable aspergillosis or zygomycosis requiring long-spt-term therapyne• Neutropenic fever in patients expected to have prolongedAg neutropenia (≥ 4 weeks)2.3For dosing in patients with neutropenic fever, see p. 111.MicafunginNOTE: Micafungin does not have activity against Cryptococcus. Aspergillosis• Acceptable uses• Infusional toxicity or acute renal failure on AmBisome® andintolerance to Voriconazole defined as serious hepatoxicity,persistent visual disturbance, or allergic reaction.• Refractory disease- for use in combination with Voriconazole orAmBisome®for definiteor probableinvasive pulmonaryaspergillosis in patients who are refractory to Voriconazole orAmBisome®alone. • Unacceptable uses• Micafungin alone or in combination with other antifungal agents isnot recommended for empiric therapy in patients with CT findingssuggestive of aspergillosis (e.g., possibleaspergillosis) withoutplans for diagnostic studies.• Micafungin does not have good in vitro activityagainstzygomycoses (Mucor, Rhizopus, Cunninghamella, etc.). Candidiasis• Acceptable uses• Treatment of invasive candidiasis due to C. glabrataor C. krusei.• Treatment of invasive candidiasis in patients who are NOT clinicallystable due to candidemia or have received prior long-term azoletherapy.17sal• Alternative treatment of recurrent esophageal candidiasis.ng• Alternative treatment of endocarditis.uftin• Unacceptable usesA • Micafungin has poor penetration into the CNS and urinary tract. It:seshould be avoided for infections involving those sites.neli• Monotherapy for zygomycoses (Mucor, Rhizopus, Cunninghamella,etc.). uid gcNeutropenic Feverfici• Micafungin can be used for neutropenic fever in patients who are notesuspected to have aspergillosis or zygomycosis.spt-neDoseAg• Candidemia, invasive candidiasis, neutropenic fever: 100 mg IV 2.Q24H3• Candidal endocarditis: 150 mg IV Q24H• Recurrent esophageal candidiasis: 150 mg IV Q24H• Invasive aspergillosis: 100–150 mg IV Q24HDrug Interactions• Close monitoring is recommended when Micafungin is used with thefollowing agents concomitantly:• Sirolimus – levels of Sirolimus may be increased, monitor forSirolimus toxicity• Nifedipine – levels of Nifedipine may be increased, monitor forNifedipine toxicity• Itraconazole – levels of Itraconazole maybe increased, monitor forItraconazole toxicityToxicity• Infusion-related reactions (rash, pruritis), phlebitis, headache, nauseaand vomiting, and elevations in hepatic enzymes.• Monitoring: AST/ALT/bilirubin at baseline and every 1–2 weeks after.PosaconazolePosaconazole is a broad spectrum azole anti-fungal agent. It has in vitroactivity against Candida, Aspergillus, Zygomycosisand Fusariumspp.Acceptable uses• Treatment of invasive zygomycosis in combination with Amphotericin B• Monotherapy for zygomycosis after 7 days of combination therapywith Amphotericin B18NOTE: Posaconazole requires up to 7 days to achieve steadysalstate concentrations. ID Consult is required.nguUnacceptable usesftin• Candidiasis/Neutropenic feverA :• Primary treatment of aspergillosisseniDose (Only available as oral suspension)eldNOTE: Each dose should be given with a full meal or with liquiduinutritional supplements if patients cannot tolerate full meals. gc• Loading dose: 200 mg PO Q6H for 7 daysfici• Maintenance dose: 400 mg PO Q8–Q12Hespt-Drug Interactionsne• Posaconazole is an inhibitor and is metabolized by cytochromeAg P4503A4; therefore, co-administration with other agents that are2.cytochrome P450 substrates, inducers, or inhibitors will result in3significant drug interactions. • You must check for potential drug interactions when initiatingPosaconazole therapy or starting a new medication in patientsalready receiving Posaconazole therapy.• Administration of the following agents with Posaconazole iscontraindicated:• Terfenadine, Astemizole, Pimozide, Cisapride, Quinidine, Sirolimus,Halofantrine and ergot alkaloids• Posaconazole inhibits metabolism of the following agents. Dosereductions and close monitoring are recommended whenPosaconazole is used with agents concomitantly:• Tacrolimus – reduce Tacrolimus dose to 1⁄3and monitor levels• Cyclosporine – reduce Cyclosporine dose to 3⁄4and monitor druglevels• Midazolam – consider dose reducing • Cimetidine, Rifabutin, Efavirenz and Phenytoin – unless the benefitoutweighs the risk, AVOIDconcomitant use. If used together,monitor effect of the drugs and consider decreasing dose whenPosaconazole is added• Statins (avoid Lovastatin and Simvastatin), vinca alkaloids, calciumchannel blockers, Digoxin, Atazanavir, Ritanovir, QTc prolongingdrugs (e.g. Amiodarone and Erythromycin) – monitor effect of thedrugs and consider decreasing dose when Posaconazole is added• Cimetidine, Rifabutin, Phenytoin, Efavirenz, Esomeprazole,Metoclopramide may decrease Posaconazole blood levels.19salToxicityng• GI upset (~40%), headaches, elevation in hepatic enzymes. Rare butufserious effects include QTc prolongation.tinA• Monitoring: AST/ALT/bilirubin at baseline and every 1–2 weeks after :senReferences:iClinical efficacy of new antifungal agents: Curr Opin Microbiol. 2006;9:483-88elPosaconazole: a broad spectrum triazole antifungal: Lancet Infect Dis. 2005; 5:775-85uid gcVoriconazoleficieNOTE: Voriconazole does not cover zygomycoses (Mucor,spt-Rhizopus, Cunninghamella, etc.).neAcceptable usesAg 2• Aspergillosis(please refer to the definitions on p. 16)..3• Oncologic neutropenic and BMT populations:1) Definite(biopsy-proven) invasive non-zygomycete filamentousfungal infections2) Probableinvasive non-zygomycete filamentous fungal infections3) Empiric therapy in patients with possibleaspergillosis (follow-up diagnostic studies are highly recommended)• Other patient populations:Definite infections or as otherwise deemed appropriate afterconsultation with the Infectious Diseases service or the AntibioticManagement Program.• Pseudallescheria boydii (Scedosporium spp.), Fusarium spp.Voriconazole is recommended as first-line therapy.• Alternative therapy for C. kruseiif susceptible and oral therapy isdesired in stable patient.Unacceptable uses• Candidiasis / Neutropenic feverVoriconazole should not be used as first-line therapy for the treatmentof candidiasis or for empiric therapy in patients with neutropenic fever.Dose• Loading dose: 6 mg/kg IV/PO Q12H x 2 doses• Maintenance dose: 4 mg/kg IV/PO Q12H• Patients receiving concomitant Phenytoinor Efavirenzshouldreceive following maintenance doses of Voriconazole due toinduced hepatic clearance by Phenytoin and Efavirenz.• Intravenous: 5 mg/kg Q12H• Oral: 400 mg Q12H (wt. ≥40 kg) OR 200 mg Q12H (wt. < 40 kg)• Efavirenz dose should be decreased to 300 mg PO daily.• Monitor Phenytoin levels and adverse events.20• Dose escalation may be necessary for some patients due tosalsubtherapeutic levels.nguTherapeutic monitoringftin• Obtaining Voriconazole trough levels should be considered in patientsA :who are:se• not responding to therapy after at least 5 days of therapy using anelimg/kg dosing strategy• receiving concomitant drugs that may increase or decreaseuid gVoriconazole levelscfi• experiencing adverse events due to Voriconazolecie• experiencing GI dysfunctionspt-• Voriconazole trough levels should be obtained 5–7 days after start ofnetherapyAg • Goal trough: 1–5.5 mcg/mL. Levels < 1 mcg/mL have been2.associated with clinical failures and levels >5.5 mcg/mL with toxicity. 3Drug Interactions• Voriconazole is an inhibitor and is metabolized by cytochrome P450;therefore, co-administration with other agents that are cytochromeP450 substrates, inducers, or inhibitors will result in significant druginteractions. • You must check for potential drug interactions when initiatingVoriconazole therapy or starting a new medication in patientsalready receiving Voriconazole therapy.• Administration of the following agents with Voriconazole iscontraindicated: • Sirolimus, Rifampin, Rifabutin, Carbamazepine, Terfenadine,Astemizole, Cisapride, Pimozide, Quinidine, long-acting barbiturates,Ritonavir (400 mg BID), St. John’s Wort, and ergot alkaloids• Voriconazole inhibits metabolism of the following agents; dosereductions and close monitoring are recommended when Voriconazoleis used with agents concomitantly:• Tacrolimus– reduce Tacrolimus dose to 1⁄3and monitor levels• Cyclosporine– reduce Cyclosporine dose to 1⁄2and monitor druglevels• Omeprazole – reduce Omeprazole dose to 1⁄2• Warfarin – monitor PT, INR levels• Ritonavir low dose (100 mg Q12H) – avoid this combination unlessbenefit outweighs risk.• Sulfonylureas, statins (avoid Lovastatin and Simvastatin), vincaalkaloids, calcium channel blockers, benzodiazepines (avoidmidazolam and triazolam), oral contraceptives, Alfentanil, andMethadone – monitor effect of the drugs and consider decreasingdose when Voriconazole is added.21salToxicityng• Visual disturbances (~30%) usually self-limited, rash, fever, elevations inufhepatic enzymes.tinA• Monitoring: AST/ALT/bilirubin at baseline and every 1–2 weeks after :senReferences:eliVoriconzole: Clin Infect Dis 2003; 36:630dVoriconazole in neutropenic fever: N Engl J Med 2002;346(4):225. uiVoriconazole TDM: CID 2008; 46:201 gcficiespt-neAg 3.322Interpreting the microbiology reporttorInterpretation of preliminary microbiology dataep ryGram-positive cocciGram-negative cocci ogAerobicAerobicoliIn clustersDiplococcus: N. meningiditis, N. gonorrhea,ob• Coagulase (+): S. aureusMoraxella catarrhaliscr• Coagulase (–): S. epidermidis, Cocco-bacillus:H. flu, Acinetobacterspp.,S. lugdunensisHACEK organisms mi In pairs/chains eh• Diplococcus, Quellung positive: t S. pneumoniaeng• Alpha-hemolytic: Viridans group tieStreptococci, Enterococcusr(faecalisand faecium)• Beta-hemolytic: erptGroup A strep (S. pyogenes),n IGroup B strep(S. agalactiae), 1.Group C, D, G strep4Anaerobic: Peptostreptococcusspp.Anaerobic: Veillonellaspp.Gram-positive rodsGram-negative rodsAerobicAerobicLarge:Bacillusspp.Lactose fermenting: Citrobacterspp.,Cocco-bacillus: Listeria monocytogenes,Enterobacterspp., E. coli, KlebsiellaLactobacillusspp.spp., Serratiaspp.*Small, pleomorphic:Corynebacteriumspp.Non-lactose fermenting Branching filaments:Nocardiaspp.,• Oxidase (–): Acinetobacterspp.,Streptomycesspp.Burkholderiaspp., E. coli(rare), Proteusspp., Salmonellaspp., Shigellaspp.,Serratiaspp.*, Stenotrophomonasmaltophilia• Oxidase (+): P. aeruginosa, Aeromonasspp.,Vibriospp., Campylobacterspp.(curved)AnaerobicAnaerobic: Bacteroidesspp.,Large: Clostridiumspp.Fusobacteriumspp., Prevotellaspp.Small, pleomorphic:P. acnes, Actinomycesspp.* Serratiaspp.can appear initially as non-lactose fermenting due to slow fermentation. The Johns Hopkins microbiology laboratory utilizes standard referencemethods for determining susceptibility. The majority of isolates aretested by the automated system. The minimal inhibitory concentration (MIC) value represents theconcentration of the antimicrobial agent required at the site of infectionfor inhibition of the organism. The MIC of each antibiotic tested against the organism is reported withone of three interpretations S (susceptible), I (intermediate), or R(resistant). The highest MIC which is still considered susceptiblerepresents the breakpoint concentration. This is the highest MIC which isusually associated with clinical efficacy. MICs which are 1⁄2–1⁄8the23breakpoint MIC are more frequently utilized to treat infections whereantibiotic penetration is variable or poor (endocarditis, meningitis,osteomyelitis, pneumonia, etc.). Similarly, organisms yielding antibioticMICs at the breakpoint frequently possess or have acquired a low-levelresistance determinant with the potential for selection of high-levelexpression and resistance. This is most notable with cephalosporins andEnterobacter spp., Serratia spp., Morganella spp., Providencia spp.,Citrobacter spp.and Pseudomonas aeruginosa. These organisms allpossess a chromosomal beta-lactamase which frequently will be over-expressed during therapy despite initial in vitrosusceptibility. Theintermediate (I) category includes isolates with MICs that approachattainable blood and tissue levels, but response rates may be lower thanfully susceptible isolates. Clinical efficacy can potentially be expected inbody sites where the drug is concentrated (e.g., aminoglycosides andbeta-lactams in urine) or when a higher dose of the drug can be used(e.g., beta-lactams). The resistant (R) category indicates the organism willnot be inhibited by usually achievable systemic concentrations of theantibiotic of normal doses. NOTE: MIC values vary from one drug to another and from onebacteria to another, and thus MIC values are NOT comparablebetween antibiotics or between organisms.24maogrbitina altspio Hsnkiop Hsnho J2.426Biliary tract infections – cholecystitis and cholangitisTREATMENTCommunity-acquired infections in patients without previousbiliary procedures AND who are not severely ill• Cefotetan 1 g IV Q12HOR• Ertapenem 1 g IV Q24HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole 500mg IV Q8HOR• PO regimen: Amoxicillin/clavulanate 875 mg PO BIDHospital-acquired infections OR patients with prior biliaryprocedures OR patients who are severely ill• Piperacillin/tazobactam 3.375 g IV Q6HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole 500mg IV Q8H In severely ill patients with cholangitis and complicated cholecystitis,adequate biliary drainageis crucial as antibiotics will not enter bile inthe presence of obstruction.Duration• Uncomplicated cholecystitis: treat only until obstruction is relieved. NOpost-procedure antibiotics are necessary if the obstruction issuccessfully relieved.• Complicated cholecystitis: 5–10 days. Trend is now favoring shorterregimens.•Biliary sepsis: 5–14 days. Shorter course favored if source controlled.Average duration is 7 days.TREATMENT NOTESMicrobiology• Gram-negative rods – E. coli, Klebsiella spp., Proteus spp., P. aeruginosa(mainly in patients already on broad-spectrum antibioticsor those who have undergone prior procedures)• Anaerobes – Bacteroides spp., generally in more serious infections, orin patients with a history of biliary manipulations• Enterococcus spp. – treatment not always indicated; use clinicaljudgment• Yeast – rare27snSpecial circumstancesotic• In cases of uncomplicated acute cholecystitis, antibiotics should beefgiven until the biliary obstruction is relieved (either by surgery, ERCP, orn ipercutaneous drain. Treatment of enterococci is controversial. Theyalnshould be treated if recovered in severely ill patients but specificmioenterococcal coverage is often not needed in mild/moderate disease.d• Yeast generally should be treated only if they are recovered from biliaryAb 1cultures, not empirically..5Reference:Biliary tract infections: Drugs 1999;57(1):81-91.IDSA Guidelines for Intra-abdominal Infections: Clin Infect Dis 2003;37:997.DiverticulitisTREATMENTMild/moderate infections – can be oral if patient can take PO• Amoxicillin/clavulanate 875 mg PO Q12HOR• Cefotetan 1 g IV Q12HOR• Ertapenem 1 g IV Q24HOR• PCN allergy: [Ciprofloxacin 400 mg IV Q12H OR Ciprofloxacin 500 mgPO Q12H] PLUSMetronidazole 500 mg IV/PO Q8HSevere infections• Ampicillin 2 g IV Q6H PLUSGentamicin (see dosing sections) PLUSMetronidazole 500 mg IV Q8HOR• Piperacillin/tazobactam 3.375 g IV Q6HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole 500mg IV Q8HDuration• Treat for 7–10 days.TREATMENT NOTESMicrobiology• Almost all infections are polymicrobial• Most commonly isolated aerobic organisms – E. coli, K. pneumoniae,Enterobacter spp., Proteus spp., Enterococcus spp.• Most commonly isolated anaerobic organisms – B. fragilis, Prevotella,Peptostreptococci28Other considerationssnCT scan is important in assessing need for drainage in severe disease.otiSome patients will present with diffuse peritonitis and pneumoperitoneum. cefnReference: ialIDSA Guidelines for Intra-abdominal Infections: Clin Infect Dis 2003;37:997.nmioPancreatitis Abd TREATMENT1.5• Mild to moderate pancreatitis – no antibiotics• Severe acute pancreatitis (SAP)* – no prophylacticantibiotics• No necrosis – no antibiotics• Sterile pancreatic necrosis – no antibiotics• Infected pancreatic necrosis* – empiric antibiotic therapy asdefined below:• Meropenem 1 g IV Q8HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole 500 mg IV Q8H* Definitions• Severe acute pancreatitis (SAP)is defined as pancreatitisassociated with one or more of the following:•> 30% pancreatic necrosis• APACHE II ≥8• More than 3 Ranson’s criteriaRanson’s criteria to predict severity of acute pancreatitis Zero HoursAge> 55WBC> 16,000/mm3Blood glucose> 200 mg/dLLactate dehydrogenase> 350 U/LAspartate aminotransferase (AST)> 250 U/L48 Hours HematocritFall by ≥10 percentBlood urea nitrogenIncrease by ≥5 mg/dL despite fluidsSerum calcium< 8 mg/dL pO2< 60 mmHgBase deficit> 4 MEq/LFluid sequestration> 6000 mL29sn• Infected pancreatic necrosisis defined as one or both of theoticfollowing:ef• CT scan with gasn i• Percutaneous aspirate or surgical specimen with organisms evidentalnon gram stain or culturemiodDurationAbFor infected pancreatic necrosis, continue antibiotics for 14 days after 1.source control is obtained. Continuation of antibiotics beyond this time5places the patient at risk for colonization or infection with resistantorganisms and drug toxicity.TREATMENT NOTES• Penicillins and cephalosporins penetrate poorly into the pancreas• Infection develops in 30–50% of patients with necrosis documented byCT scan or at the time of surgery.• Peak incidence of infection occurs in the 3rd week of disease• Prophylactic antibiotics have been associated with a change in thespectrum of pancreatic isolates from enteric Gram-negatives to Gram-positive organisms and fungi.• There is insufficient evidence to recommend selective gutdecontamination in management of pancreatitis.References:Lack of utility of prophylactic antibiotics: Ann Surg 2007;245:674.Guidelines for management of SAP: Crit Care Med 2004;32:2524.Ranson’s criteria: Surg Gynecol Obstet 1974;139:69.30PeritonitissnotiDEFINITIONScePrimary peritonitisis spontaneous infection of the peritoneal cavity,fn iusually associated with liver disease and ascites [spontaneous bacteriaalnperitonitis (SBP)]. miSecondary peritonitisis infection of the peritoneal cavity due to spillageoof organisms into the peritoneum, usually associated with GI perforation.Abd Tertiary peritonitisis a recurrent infection of the peritoneal cavity1.following an episode of secondary peritonitis.5Primary peritonitis/Spontaneous bacterial peritonitis (SBP)TREATMENT• Ceftriaxone 1 g IV Q24H is preferred.• Amoxicillin/clavulanic acid 875 mg PO BID is the preferred oralregimen.• Moxifloxacin 400 mg IV/PO Q24H can be used in PCN-allergic patientswho have NOT been taking fluoroquinolone for SBP prophylaxis.Duration• Treat for 5 days.PROPHYLAXISCirrhotic patients with gastrointestinal hemorrhage• Norfloxacin 400 mg PO BID for 7 days • Ceftriaxone 1 g IV Q24H can be used only if patient is NPO, thenswitch to Norfloxacin 400 mg PO BID once bleeding is controlled Non-bleeding cirrhotic patients with ascites• Norfloxacin 400 mg PO dailyOR• TMP/SMX 1 DS PO once daily TREATMENT NOTESMicrobiology• Gram-negative rods (Enterobacteriaceae, esp. E. coliand K.pneumoniae), S. pneumoniae, enterococci, and other streptococci.• Polymicrobial infection should prompt suspicion of GI perforation.Diagnostic criteria• 250 PMN per mm3of ascitic fluid.• Positive culture with < 250 PMN should prompt repeat tap. If PMN >250 OR culture remains positive, patient should be treated.31snFollow-upotic• Consider repeat paracentesis after 48 hours of therapy.ef• Consider changing antibiotics if ascites fluid PMN has not dropped byn i25% after 48 hours and/or patient is not clinically responding.alnmiNotes on prophylaxis against SBPod• All patients with cirrhosis and upper GI bleed should receive prophylaxisAbfor 7 days (50% develop SBP after bleed). 1.• Patients who get SBP should get lifelong prophylaxis to prevent future5episodes (40–70% risk of recurrence in 1 year).• Prophylaxis should be considered for those with low proteinconcentrations in ascites (< 10 g/L) or immunosuppression but mustbe carefully weighed against the risk of resistance.Reference:Diagnosis, treatment and prophylaxis of SBP: J Hepatol 2000;32:142.Management of variceal hemorrhage in cirrhosis: Hepatology 2007;46:922–38.Secondary peritonitis/GI perforationTREATMENTPerforation of esophagus, stomach, small bowel, colon, orappendixPatient mild to moderately ill• Cefotetan 1 g IV Q12HOR• Ampicillin 2 g IV Q6H PLUSGentamicin (see dosing section) PLUSMetronidazole 500 mg IV Q8HOR• Ertapenem 1 g IV Q24HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole 500mg IV Q8HPatient severely ill or immunosuppressed• Piperacillin/tazobactam 3.375 g IV Q6HOR• PCN allergy: Ciprofloxacin 400 mg IV Q12H PLUSMetronidazole500mg IV Q8HEmpiric antifungal therapy is generally not indicated for GI perforationunless patient has one of the following risk factors:Esophageal perforation, immunosuppression, prolonged antacid orantibiotic therapy, prolonged hospitalization, persistent GI leak.32Recommendations for patients who are clinically stable and have notsnreceived prior long-term azole therapy:oti• Fluconazole 400-800 mg IV/PO Q24HcefORn i• Amphotericin B 0.7 mg/kg IV Q24H alnRecommendations for patients who are NOT clinically stable or havemioreceived prior long-term azole therapy:• Micafungin 100 mg IV Q24H Abd 1OR.5• AmBisome®3 mg/kg IV Q24HDuration of therapy for secondary peritonitis/GI perforationStomachSmall Bowel ColonAppendixUncomplicatedDefinitionOperated onOperated onOperated on Non-necrotic orwithinwithinwithingangrenous24 hours12 hours12 hoursappendix Duration24–48 hours24–48 hours24–48 hours24 hoursComplicatedDefinitionLate operation or no operation; or necrotic/gangrenous appendixDuration5-7 daysTREATMENT NOTES• Causative agents for small bowel, colon, appendix: anaerobes (esp. B. fragilis), Enterobacteriaceae (esp. E. coli, K. pneumoniae,Enterobacter spp., Proteus spp.); infections usually polymicrobial. • Pathogens causing tertiary peritonitis are variable and are oftenresistant to or not covered by the initial antimicrobial regimen; thus, achange in antimicrobials is advised.• A change in antimicrobials therapy should be considered in patientswith hospital-acquired infections who are already on antimicrobials. • Treatment of enterococci remains controversial but may be of benefitin critically ill patients.• Treatment of Candida spp. is generally indicated only when they arerecovered from blood or are the primary organism in the peritonealculture.• Postoperative antibiotics for appendicitis are unnecessary unless thereis clinical evidence of peritonitis, abscess, or gangrene.• Antibiotics are adjunctive to source control, which is an absolutenecessity.• Lack of source control is defined as on-going contamination and/or anundrained collection of infection.33snoPeritonitis related to peritoneal dialysisticeTREATMENTfnMild to moderate illness: intraperitoneal therapy is preferred in ialnmost cases.miAnuric patientod• Cefazolin 15 mg/kg in one bag Q24H (1 g if patient < 65 kg) PLUSAb• Gentamicin 2 mg/kg in one bag loading dose, then Gentamicin 1.0.6mg/kg in one bag Q24H5Patient with urine output > 100 mL/day• Ceftazidime 1 g in one bag Q24HSevere illness: systemic therapy is preferred.• FIRST DOSE: Vancomycin (see dosing section, p. 138) IV PLUS ONEofthe following:[Gentamicin 2 mg/kg IV OR Ceftazidime 1 g IV OR Ciprofloxacin 400mg IV]• MAINTENANCE DOSE: Dose per drug levels and/or renal function (Seedosing section p. 138 and p. 142)Duration of tailored therapy: 10–14 daysTREATMENT NOTESMicrobiology• Most cases caused by contamination of the catheter• Cultures may be negative in 5–20%• Gram-positive cocci (S. aureus, coagulase-negative staphylococci,Enterococcus spp.), Gram-negative rods, yeast (much less common)Diagnosis• All patients with suspected PD-related peritonitis should have PD fluidsampled for cell count, differential, gram stain, culture ANDamylase.WBC > 100/mm3with > 50% PMN suggests infection.• Elevated amylase suggests pancreatitis or bowel perforation.• In symptomatic patients with cloudy fluid accompanied by abdominalpain and/or fever, empiric treatment should be started given the highlikelihood of infection.• In symptomatic patients with clear fluid, another PD fluid exchange,with a dwell time of at least 2 hours, should be sampled. The decisionto start empiric therapy in these cases will depend on how sick thepatient appears.• In asymptomatic patients with cloudy fluid, it is reasonable to delaytherapy pending the results of cell count, gram stain, and culture.References:ISPDGuidelines for Peritoneal Dialysis-related Infections: Perit Dial Int 2005;25:107.34Clostridium difficile infection (CDI))ICDTREATMENT( n• STOP ALL ANTIMICROBIAL AGENTS WHENEVER POSSIBLE.otic• Oral therapy must be used whenever possible as the efficacy of IVefnMetronidazole is poorly established for CDI and there is no efficacy ofieIV Vancomycin for CDI.cilfifTreatment depends on clinical severity diInfection severityClinical manifestationsmuAsymptomatic C. difficileantigen or PCR positive without diarrhea, dicarriageileus, or colitistrisoMild or moderateC. difficile PCR positive with diarrhea but noCl manifestations of severe disease2.SevereC. difficile PCR positive with diarrhea and one or more5of the following attributable to CDI:• WBC ≥15,000 • Increase in serum creatinine > 50% from baselineSevere ComplicatedCriteria as above plus one or more of the followingattributable to CDI:• Hypotension• Ileus • Toxic megacolon or pancolitis on CT• Perforation• Need for colectomy• ICU admission for severe diseaseInfection SeverityTreatmentAsymptomatic Do NOT treat; treatment can promote relapsing carriagediseaseMild or moderate• Metronidazole 500 mg PO/NGT Q8H Unable to tolerate oral therapy • Metronidazole 500 mg IV Q8H (suboptimal; see noteat start of CDI section above)Severe• Vancomycin solution 125-250 mg PO/NGT Q6H(preferred)OR• Vancomycin capsules 125 mg PO Q6HSevere Complicated• Consult surgery for evaluation for colectomy and ID • Vancomycin solution 500 mg by NGT Q6H PLUSMetronidazole 500 mg IV Q8H Unable to tolerate oral therapy or complete ileus • Vancomycin 500 mg in 100 ml NS Q6H as retentionenema via Foley catheter in rectum +Metronidazole500 mg IV Q8H 35)IOther indications for oral Vancomycin useCD(• No response to oral Metronidazole after 5 days of therapy no• Second episode of recurrent diseasetice• Patients with significant side effects to Metronidazolefn• Patients who are pregnantie• Consider in patients > 80 years given reports of increased morbiditycilfifrom CDI.f dimDurationu• 10–14 daysiditrRecurrent diseaseso• Resistance to Metronidazole or Vancomycin has not been documentedCl 2conclusively..5• Recurrent disease after a complete course of therapy occurs in ~ 25%of patients. Relapse is due to failure to eradicate spores (60%) oracquisition of a new strain (40%). Document recurrent disease withrepeat stool testing. • First recurrence should be treated the same as the initial episode. • Second recurrence should be treated with Vancomycin taper followedby pulse dosing. • If serious or multiple recurrences, consult ID.Vancomycin taper regimen125 mg 4 times daily x 10–14 days125 mg BID X 7 days125 mg daily X 7 days125 mg every 2–3 days for 2–8 weeks (pulse dosing)TREATMENT NOTESDiagnosis• Do NOT send stool for C. difficiletesting if patients do not havediarrhea, ileus, or colitis. • Stool for C. difficiletesting should be collected prior to startingtreatment for C. difficile.• Specimens should be hand carried to the laboratory as soon aspossible after collection. If they cannot be transported promptly, thesamples should be refrigerated. • Specimens collected outside of the institution should be transported at4°C to avoid degradation of toxin which can lead to false negative results.• The JHH microbiology lab uses a two-step algorithm for C. difficiledetection. Stools are screened with an assay that detects an antigenproduced by both toxigenic (i.e. disease causing) and non-toxigenic (i.e. non-disease causing) strains. The negative predictive value of thistest is 95%. Antigen-positive samples are automatically tested for 36C. difficiletoxin B gene using a real-time PCR assay. The sensitivity of)the real time PCR is 91% compared to cell culture neutralization andCDI(84% compared to toxigenic culture. no• There is limited utility to sending repeat C. difficiletests. If the antigenticor toxin tests are negative and clinical suspicion is high for CDI, collectefna repeat stool sample and call the microbiology lab to ask for aietoxigenic stool culture for C. difficile. Stool samples should be sentcilfibefore therapy for C. difficile is initiated.f diManagementmu• Surgical intervention for total colectomy should be considered early ifdipatient is clinically unstable secondary to CDI.tris• Most patients with severe CDI should undergo abdominal CT to rule outoCltoxic megacolon or pancolitis. 2.• Early therapy appears to be important, especially in elderly patients. It5may be necessary to discontinue the offending agent and initiate therapywith Metronidazole or Vancomycin while the toxin assay is pending.• Do NOT send follow-up C. difficile toxins to document resolution ofdisease.• Do not use antimotility agents.• The offending antimicrobial agents should be discontinued. Ifantimicrobials are still required, it is best to avoid Clindamycin,cephalosporins, and fluoroquinolones.• Prophylactic use of oral Metronidazole or Vancomycin in patientsreceiving antimicrobial therapy for treatment of underlying infection(other than CDI) is not recommended and may increase the patient’srisk for CDI.References:Diagnosis of CDI: Clin Infect Dis 2008; 46:S12-8.Treatment of CDI: Clin Infect Dis 2008; 46:S32-42.Lack of utility of treating CDI carriers: Ann Intern Med 1992; 117:297-302.Colectomy in CDI: Ann Surg 2007; 245:267-72.37aehInfectious diarrhearar• For treatment of C. difficileinfection, see p. 35. dis• Carefully assess the patient before prescribing antimicrobials.uo• Most infectious diarrhea is self limited and only requires supportiveticemanagement.fn• Treatment with antibiotics is not recommended for most mild-moderate I3.disease; see specific indications in table below.5• Viral pathogens, such as Norovirus and Rotavirus commonly causediarrhea and do not require antibiotics.• Antibiotic use may lead to adverse outcomes (e.g. hemolytic uremicsyndrome with Shiga toxin-producing E. coli).• Antimotility agents should not be used in patients with bloody diarrhea,fever, or elevated WBC.Microbiology • Common non-viral pathogens in acute community-acquired diarrhea:Salmonella, Shigella, Shiga toxin-producing E. coli, Campylobacter, C. difficile(usually with antibiotic exposure). • Nosocomial diarrhea: C. difficile• Persistent diarrhea if immunocompromised (most likely causes varydepending on type of immunocompromise): Giardia, Cryptosporidium,Cyclospora, Isospora, Microsporidia, Cytomegalovirus (CMV).Diagnosis• Not every diarrheal illness requires stool culture. Decision to testshould be based on suspicion for specific pathogens and/or clinicaljudgment of illness severity.• Patients with febrile diarrheal illnesses with clinical features ofmoderate to severe disease should receive empiric therapy only after afecal specimen is obtained for appropriate testing.• Fecal specimens from patients hospitalized for > 3 days should not besubmitted for routine stool culture unless a high suspicion for specificpathogen exists and/or if the patient is immunocompromised. • Multiple stool examinations for ova and parasites (O&P) are of lowyield.• Fecal leukocyte/lactoferrin assessments should not be used todetermine the therapeutic approach.38Treatment of infectious diarrheaaehOrganism/Indications for treatmentTreatmentrariBacteria dsCampylobacterspp.• Azithromycin 500 mg PO daily for 1–3 daysuotiTreatment recommended for:c• Severe illnessef• Age < 6 months or > 50 yearsn I• Gross blood in stool3.• High fever5• Worsening or relapsing symptoms• Pregnancy• Immunocompromised hostE. coli(enterotoxigenic, enteropathogenic,• Norfloxacin 400 mg PO BID enteroinvasive) or empiric therapy of ORtraveler’s diarrhea• Ciprofloxacin 500 mg PO BIDORDuration:1–3 daysShiga toxin producingE. coli(including Treatment not recommended. AntibioticE. coli0157:H7)use associated with development ofhemolytic uremic syndrome.Non-typhoid Salmonellaspp.• Norfloxacin 400 mg PO BID (not forbacteremia)Treatment recommended for:OR• Severe illness requiring hospitalization• Ciprofloxacin 500 mg PO BID • Age < 6 months or > 50 yearsOR• Bacteremia• TMP/SMX 160/800 mg PO BID • Presence of prostheses(if susceptible)• Valvular heart diseaseOR• Severe atherosclerosis• Ceftriaxone 1g IV Q24H• Malignancy or other immunocompromiseDuration:5–7 days; 14 days forimmunocompromised hostShigellaspp.• TMP/SMX 160/800 mg PO BID (if susceptible)Treatment always recommended even if resultORreturns when patient is asymptomatic.• Norfloxacin 400 mg PO BID (not for bacteremia) OR• Ciprofloxacin 500 mg PO BID Duration:3 days; 7 days for immuno-compromised hostVibrio parahaemolyticus• Ciprofloxacin 500 mg PO BID x 3 daysNote: Associated with shellfish consumptionTreatment recommended for severe illnessYersiniaspp.• TMP/SMX 160/800 mg PO BID x 3–5days (if susceptible)Treatment recommmended for:OR• Immunocompromised host• Ciprofloxacin 500 mg PO BID x 3 days• BacteremiaOR• Pseudoappendicitis syndrome• Doxycycline 100 mg PO BID x 3 days(not for bacteremia)39aehParasitesrarEntamoeba histolytica• Metronidazole 750 mg PO TID x 5–10idays dsTreat all (even asymptomatic)ORuo• Tinidazole 1 g PO Q12H x 3 daystiE. dispar & E. moshkovskiiinfections do not cerequire treatment• PLUSall patients should receivefnParomomycin 500 mg PO TID x 7 days I3after the course of 1st agent complete.5Asymptomatic patients• Paromomycin 500 mg PO TID x 7 daysGiardiaspp.• Metronidazole 250-500 mg PO TID x7–10 daysOR•Tinidazole 2 g PO onceReferences: IDSA Guidelines for Management of Infectious Diarrhea; Clin Infect Dis 2001;32:331–50.Infectious diarrhea in developed and developing countries: J Clin Gastroenterol 2005:39:757–773.40Helicobacter pyloriinfectionnotiEstablished indications for testing for H. pyloriand treatingcefpositive patients ni• Active peptic ulcer disease (PUD) – gastric or duodenalori• Confirmed history of PUD (not previously treated for H. pylori)yl p• Gastric MALT lymphoma (low grade)ert• Following resection of gastric cancerca• Family history of gastric cancer obcOther indications where testing for H. pyloriand treating positiveelipatients can be considered: nonulcer dyspepsia, GERD, persons H4using NSAID, unexplained iron deficiency anemia, family members of.5patients with H. pyloriwith mild dyspepsia.First-line treatment • Amoxicillin 1 g PO Q12H PLUSClarithromycin 500 mg PO Q12H PLUSPantoprazole 40 mg PO Q12HOR• PCN allergy• Clarithromycin 500 mg PO Q12H PLUSMetronidazole 500 mg POQ12H PLUSPantoprazole 40 mg PO Q12HOR• Tetracycline 500 mg PO Q6H PLUSMetronidazole 500 mg POQ8H PLUSBismuth subsalicylate 525 mg PO Q6H PLUSPantoprazole 40 mg PO Q12H• Duration:10–14 daysDocumented recurrence of H. pylori disease • If possible, avoid antibiotics previously used to treat H. pylori• Tetracycline 500 mg PO Q6H PLUSMetronidazole 500 mg PO Q8HPLUSBismuth subsalicylate 525 mg PO Q6H PLUSPantoprazole 40mg PO Q12H• Duration:14 daysTREATMENT NOTESDiagnosis • PPIs and antibiotics should be withheld for at least 2 weeks prior totesting.• H. pyloristool antigen is the only FDA approved test (>90% sensitivityand specificity). • Urea breath test may be optimal but not commonly available.• Endoscopy PLUSrapid urease test (80–95% sensitivity; 92–100%specificity). • H. pylori serology does not document current infection. 41noManagementtic• First line treatment eradication rates estimated between 70–80%.efnFailure most often due to Clarithromycin resistance and/or non-iiadherence.oryl• H2-receptor antagonists (e.g., ranitidine) can be substituted for the PPI pif patients are unable to tolerate PPIs or if drug interactions are aertcconcern.a• Amoxicillin PLUSTetracycline can NOT be used together in treatmentobcidue to low response rates. el• In patients with positive test results endoscopy is mandatory for age H4.>45-50 years, presence of mass GI bleeding, anemia, weight loss, or5family history of gastric cancer. • Test of cure is recommended > 4–8 weeks post treatment. References:Maastricht III Consensus Report. Gut2007;56:772-781.ACG Guidelines. Am J Gastroenterol2007;102:1808-1825.42Management of catheter-associated snobloodstream infections (CA-BSI)ticeDiagnosisfn i• If there is more than minimal erythema or ANY purulence at the exitmsite, the catheter is likely infected. It should be removed and replacedaeat a different site.trs• Two sets of blood cultures should be drawn with AT LEAST one (andodopreferably both) from peripheral sites. Blood cultures drawn through blnon-tunneled catheters are more likely to yield contaminants. One setedtof cultures may be drawn through a catheter if it is tunneled.aci• The utility of cultures of the catheter itself is not well defined, andossshould ONLY be sent when there is a clinical suspicion of infection, NOTaroutinely when lines are removed. They MUST be accompanied by twoer-tsets of blood cultures obtained as detailed above.eht• Technique: The exit site should be cleaned with alcohol. TheaC catheter should be grasped a few centimeters proximal to the exit5.site. A 5 cm segment of catheter including the intradermal5segment just distal to the insertion site should be cut off with sterilescissors and placed in a sterile container.• In instances where the blood and catheter are cultured at the sametime and the blood cultures are negative but the catheter culture ispositive, antibiotics are generally not recommended, even for patientswith valvular heart disease or immunosuppression. • The exception is patients whose catheter tips grow S. aureusandhave negative blood cultures. These patients should receive 5–7days of antibiotics.• All patients should be followed closely, and repeat cultures shouldbe sent if clincally indicated.• When a catheter-associated BSI is associated with catheterdysfunction, consider the possibility of suppurative thrombophlebitis.Management• Antibiotics should generally be withheld in febrile patients withintravenous catheters and no other clear source of infection pendingthe results of blood cultures. Exceptions include immunosuppressed orcritically ill patients, patients with valve replacement or other hardwarein place, or instances where there is pus at the catheter site. Empiric treatment – immunosuppressed or critically ill patients• Vancomycin (see dosing section, p. 138) ±[Cefepime 1 g IV Q8H ORPiperacillin/tazobactam 4.5 g IV Q6H]OR• PCN allergy: Vancomycin (see dosing section, p. 138) ±Ciprofloxacin400 mg IV Q8H43snEmpiric treatment – Gram-positive cocci in clusters in 2 or moreoticsets of blood culturesef• Vancomycin (see dosing section, p. 138)n imNOTE:The microbiology lab performs a coagulase and thermonucleaseaetest on all Gram-positive cocci in clusters isolated from blood culturestrswithin 3 hours. A note is placed in EPR if the tests are positive, indicatingodS. aureus. No EPR note is generated if the tests are negative, indicatingolcoagulase-negative staphylococci in the majority of cases (90%). If a bedpatient has one set of blood cultures growing Gram-positive cocci intaclusters that are not coagulase-positive then treatment should be withheldcioand additional blood cultures obtained in the majority of situations.ssaer-Coagulase-negative staphylococci (CoNS)tehNOTE:Single positive cultures of CoNS should NOT be treated taunless they are confirmed by follow-up cultures, the patient isC 5immunosuppressed and/or critically ill, or the patient has implanted.5hardware. In these cases, treatment can be started but repeat culturesshould be sent PRIOR to initiation of therapy to confirm the diagnosis.• Vancomycin (see dosing section, p. 138) Change to• Oxacillin 2 g IV Q4H if susceptible (preferred to Vancomycin)Duration: • 5–7 days if catheter removed (preferred)• 10–14 days if catheter salvage attemptStaphylococcus aureus• Vancomycin (see dosing section, p. 138)Change to• Oxacillin 2 g IV Q4H if susceptibleOR• Non-anaphylactic PCN allergy: Cefazolin 2 g IV Q8HOR• Anaphylactic PCN allergy or MRSA: Vancomycin (see dosing section, p. 138)TREATMENT NOTES• Remove catheter. High relapse rates if catheter is not removed.• Vancomycin is inferior to Oxacillin for treatment of MSSA.• Patients with S. aureusbacteremia should have an echocardiogram torule out endocarditis. Transthoracic echo is acceptable only if the studyadequately views the left-sided valves; most experts recommend TEE.• 14 days is the minimum course of therapy for S. aureusbacteremia44and should only be considered if endocarditis and other metastaticsninfection have been ruled out. oti• Linezolid should not be used as monotherapy for treatment of cefS. aureusbacteremia n imaEnterococcus faecalisetrNOTE:Can be contaminants. Draw repeat cultures to confirm beforesstarting treatment. All E. faecalisblood isolates at JHH are susceptible toodolAmpicillin, which should be used unless the patient has a PCN allergy. bed• Ampicillin 2 g IV Q4H ±Gentamicin 1 mg/kg IV Q8H (see treatmenttanotes below)ciosORsa-• PCN allergy: Vancomycin (see dosing section p. 138) ±Gentamicin 1ertemg/kg IV Q8H (see treatment notes below)htaDuration:10–14 daysC 5.Enterococcus faecium5NOTE:Can be contaminants. Draw repeat cultures to confirm beforestarting treatment. The majority (78%) of E. faeciumblood isolates atJHH are resistant to Vancomycin. If the isolate is susceptible toAmpicillin or Vancomycin, these agents should be used preferentially atthe doses listed above for E. faecalisbacteremia.• Linezolid 600 mg IV/PO Q12HOR• Quinupristin/dalfopristin 7.5 mg/kg Q8HTREATMENT NOTES• Consider echocardiogram if there is persistent bacteremia (>3 days)on antibiotics.• Do not use Gentamicin if the lab reports no synergy with a cell wallagent.• If synergy is present, Gentamicin should be added to Ampicillin orVancomycin in the treatment of endocarditis; however, the addition ofGentamicin does not appear to change outcomes in CA-BSI caused byEnterococcus in the absence of endocarditis if catheter has beenremoved.• Do not use Gentamicin with Linezolid or Quinupristin/dalfopristin givenlack of supportive evidence for synergy. Gram-negative bacilli• Cefepime 1 g IV Q8HOR• Piperacillin/tazobactam 4.5 g IV Q6H45snORotic• PCN allergy: Ciprofloxacin 400 mg IV Q8HefThese are anti-pseudomonal doses. Lower the dosesn im(Piperacillin/tazobactam 3.375 g IV Q6H, or Ciprofloxacin a[400 mg IV Q12H or 500 mg PO Q12H]) if Pseudomonasis NOTetrsrecovered and organisms are NOT susceptible to agents with aodnarrower spectrum of activity.oDuration: 10–14 days bledtaciTREATMENT NOTESos• Catheters are less commonly the source of the infection; however,samost advocate catheter removal if the catheter is the source.-ertehCandidaspp.taC 5• Refer to p. 99 for treatment of candidemia.5GENERAL TREATMENT NOTES ON CATHETER-ASSOCIATED BSIsMicrobiology – most common pathogens:Coagulase-negativestaphylococci, Enterococci, S. aureus,Gram-negative bacilli, CandidaspeciesCatheter salvage• Catheter removal is STRONGLY recommended for infections with S. aureus, yeast and Pseudomonas,as the chance of catheter salvageis low and the risks of ongoing infection can be high.• Catheters associated with tunnel infections CANNOT be salvaged andshould be removed.• Catheter salvage can be considered in CA-BSIs caused by coagulase-negative staphylococci if the patient is clinically stable.• When catheter salvage is attempted, antibiotics should be giventhrough the infected line.• Duration of treatment for catheter salvage is similar to duration oftreatment when the catheter is removed. • Antibiotic lock therapy, in which an antibiotic is infused into the catheterand left in place, can be considered in the treatment of tunneledcatheter infections due to less virulent pathogens such as CoNS andsome Gram-negatives. Call the Antibiotic Management Program (7-4570) for details.Reference:IDSAGuidelines for the Diagnosis and Management of Intravascular Catheter-relatedInfections: Clin Infect Dis 2009;49:1-45.46Treatment of native valve endocarditisstidiarNOTES:co• Beta-lactams are highly preferableto Vancomycin if the organism isndsusceptible and if the patient is not severely allergic. Some advocate E6PCN desensitization for allergic patients..5• Infectious Diseases consultation is advised for cases of left-sidedinfective endocarditis and prosthetic valve endocarditis, particularly inthose in which the preferred antibiotic cannot be used or in which theorganism is resistant to usual therapy.• Therapeutic monitoring: • Vancomycin• Goal trough level: 15–20 mcg/mL• Gentamicin for Gram-positive synergy• Daily dosing• Goal trough level: <1 mcg/mL• Traditional dosing (Q8H)• Goal peak level: 3–4 mcg/mL• Goal trough level: <1 mcg/mL• See p. 132 and p. 138 for detailsViridans streptococci or S.boviswith PCN MIC ≤0.12 mcg/mL • Penicillin G 3 million units IV Q4H for 4 weeksOR• Ceftriaxone 2 g IV/IM Q24H for 4 weeksOR• [Penicillin G 3 million units IV Q4H OR Ceftriaxone 2 g IV/IM Q24H for 2weeks] PLUSGentamicin 3 mg/kg IV Q24H for 2 weeksOR• PCN allergy: Vancomycin (see dosing section, p. 138) for 4 weeksCriteria for 2 week treatment:• Patient does not have cardiac or extracardiac abscess• CrCl >20 mL/min• Patient does not have impaired 8th cranial nerve function • Patient does not have Abiotrophia, Granulicatella, or Gemellaspp.infectionViridans streptococci or S. boviswith PCN MIC >0.12 mcg/mLand ≤0.5 mcg/mL • [Penicillin G 4 million units IV Q4H OR Ceftriaxone 2 g IV/IM Q24H for 4weeks] PLUSGentamicin 3 mg/kg IV Q24H for the first 2 weeks oftherapy47stiORiard• PCN allergy: Vancomycin (see dosing section, p. 138) for 4 weeks condViridans streptococci or S. boviswith PCN MIC >0.5 mcg/mL E6• Treat as Enterococcal endocarditis.5TREATMENT NOTES• All patients with S. bovisendocarditis should undergo GI work-up to ruleout underlying cancer.Staphylococcus aureus– Methicillin susceptible, native valve,right-sided involvement only• Oxacillin 2 g IV Q4H for 2 weeks• Use Nafcillin for Oxacillin-induced hepatitisCriteria for 2-week treatment:• ADEQUATE transthoracic echo (TTE) or transesophageal echo(TEE) to rule out left-sided involvement, as some series report ahigh frequency of left-sided disease• Treatment is with Oxacillin or Nafcillin • Patient does not have AIDS (CD4 <200)• Patient does not have a vascular prosthesis (dialysis graft, etc)• Blood cultures are negative within 4 days after starting therapy • There is no evidence of embolic disease OTHER than septicpulmonary emboli• Vegetations are all <2 cm in size • If patient does not meet criteria for 2-week treatment, treat as MSSA,native valve, left-sided endocarditis• Oral treatment with Ciprofloxacin 750 mg BID PLUSRifampin 300 mgBID for 4 weeks has been effective in 2 studies BUT has never beenstudied in the outpatient setting where compliance may be problematicStaphylococcus aureus– Methicillin susceptible, native valve,left-sided involvement• Oxacillin 2 g IV Q4H OR• Non-anaphylactic PCN allergy: Cefazolin 2 g IV Q8H OR• Anaphylactic PCN allergy: Strongly consider PCN desensitization orVancomycin (see dosing section, p. 138)• The addition of Gentamicin to a beta-lactam may help clear blood culturesfaster but does not appear to affect mortality. It particularly should beavoided in the elderly and in those with baseline renal impairment.48sStaphylococcus aureus– Methicillin resistant, native valveti• Vancomycin (see dosing section, p. 138)diarcoDurationnd• Uncomplicated: 4 weeks E6.• Complicated (perivalvular abscess formation, metastatic complication,5poor controlled diabetes mellitus, MRSA): 6 weeks• ID and cardiac surgery consults recommended for complicateddiseasesS. pneumoniae, and Group A streptococci• Penicillin G 3 million units IV Q4H for 4 weeksOR• Ceftriaxone 2 g IV Q24H for 4 weeksOR• Cefazolin 2 g IV Q8H for 4 weeksOR• Anaphylactic PCN allergy: Vancomycin (see dosing section, p. 138) for4 weeks • For S. pneumoniae, if PCN MIC ≥0.1, consult IDGroups B, C and G streptococci• Penicillin G 3 million units IV Q4H for 4–6 weeks ±Gentamicin 3 mg/kg IV Q24H for the first 2 weeks of therapyOR• Cefazolin 2 g IV Q8H for 4–6 weeks ±Gentamicin 3 mg/kg IV Q24Hfor the first 2 weeks of therapyOR• Anaphylactic PCN allergy: Vancomycin (see dosing section, p. 138) for4–6 weeks ±Gentamicin 3 mg/kg IV Q24H for the first 2 weeks oftherapy• Consider an ID ConsultEnterococci with PCN MIC ≤16 mcg/mL AND Gentamicin MIC ≤500 mcg/mL• [Ampicillin 2 g IV Q4H OR Penicillin G 4 million units IV Q4H] PLUSGentamicin 1 mg/kg IV Q8H BOTHfor 4–6 weeks OR• PCN allergy: Strongly consider PCN desensitization if PCN allergy isanaphylactic or Vancomycin (see dosing section, p. 138) PLUSGentamicin 1 mg/kg IV Q8H BOTHfor 4–6 weeks• Treat for 4 weeks only when symptoms have been present for < 3months AND there is a prompt response to therapy49sti• If PCN susceptible and Gentamicin resistant but Streptomyciniardsusceptible, substitute Streptomycin 7.5 mg IV/IM Q12H forcoGentamicinnd E6Enterococci – PCN, Vancomycin, or Aminoglycoside resistant.5• Consult IDHACEK organisms (Haemophilus parainfluenzae, H. aphrophilus,Actinobacillus actinomycetemcomitans, Cardiobacteriumhominus, Eikenella corrodens, Kingella kingae) • Ceftriaxone 2 g IV/IM Q24H for 4 weeksOR• Ampicillin/sulbactam 3 g IV Q6H for 4 weeksOR• Anaphylactic PCN allergy: Consult IDGram-negative organisms, culture negative endocarditis, orfungal endocarditis• Consult IDTreatment of prosthetic valve endocarditis• Generally caused by staphylococci in the first 1–2 years following valvereplacement (both S. aureusand coagulase-negative staph). Etiologiesare similar to native valve infections 2 or more years post-op.• Medical treatment alone is often NOT effective.• All patients should have a TEE.Empiric therapy• Vancomycin (see dosing section, p. 138) PLUSGentamicin 1 mg/kg IVQ8H AND• Rifampin 300 mg PO Q8H after blood cultures have clearedViridans streptococci or S. boviswith PCN MIC ≤0.12 mcg/mL • [Penicillin G 4 million units IV Q4H OR Ceftriaxone 2 g IV/IM Q24H] for 6weeks ±Gentamicin 3 mg/kg IV Q24H for first 2 weeks of therapyOR• PCN allergy: Vancomycin (see dosing section, p. 138) for 6 weeksViridans streptococci or S. boviswith PCN MIC >0.12 mcg/mL • [Penicillin G 4 million units IV Q4H OR Ceftriaxone 2 g IV/IM Q24H]PLUSGentamicin 3 mg/kg IV Q24H for 6 weeks50ORsti• PCN allergy: Vancomycin (see dosing section, p. 138) for 6 weeksdiarcStaphylococcus aureus—Methicillin susceptibleond• Oxacillin 2 g IV Q4H for 6 weeks PLUSGentamicin 1 mg/kg IV Q8H for E1st 2 weeks of therapy 6.5AND• Rifampin 300 mg PO Q8H for 6 weeks after blood cultures havecleared• ID and cardiac surgery consults recommendedStaphylococcus aureus – Methicillin resistant or Coagulase-negative Staphylococci*• Vancomycin (see dosing section, p. 138) for 6 weeks PLUSGentamicin 1 mg/kg IV Q8H for the first 2 weeks of therapyAND• Rifampin 300 mg PO Q8H for 6 weeks after blood cultures havecleared* If coagulase-negative staphylococci is susceptible to Oxacillin with MIC≤0.5, then treat as S. aureus– Methicillin susceptible.• ID and cardiac surgery consults recommendedGram-negative organisms or culture negative endocarditis• Consult IDDUKE CRITERIA FOR INFECTIVE ENDOCARDITISDiagnostic criteria (Modified Duke criteria)Definite endocarditis• Presence of 2 major criteria OR 1 major AND 3 minor OR 5 minorPossible endocarditis• Presence of 1 major AND 1 minor OR 3 minor criteriaRejected endocarditis• Firm alternate diagnosis that explains ALL manifestations of IE(NOTE: simply having another infection does NOT excludeendocarditis)Major criteriaMicrobiologic• Two separate blood cultures positive for a typical organism: viridansstreptococci, S. bovis, HACEK, S. aureus, Enterococcusspp.• Persistent bacteremia with any organism as evidenced by: 2 positiveblood cultures drawn at least 12 hours apart OR 3/3 positive bloodcultures with at least 1 hour between the first and lastOR themajority of more than 4 cultures positive from any time period.51sti• Positive Coxiella burnetti(Q fever) culture or serology. iardEchocardiographic (TEE strongly recommended for prosthetic valve)co• Vegetation (on valve or supporting structure OR in path ofndregurgitant jet) E6• Abscess.5• New dehiscence of prosthetic valvePhysical exam• NEW regurgitant murmur (worsening of old murmur is NOTsufficient)Minor criteria• Predisposing condition: previous endocarditis, injection drug use,prosthetic valve, ventricular septal defect, coarctation of the aorta,calcified valve, patent ductus, mitral valve prolapse with regurgitation,IHSS or other valvular heart disease • Fever ≥38.0°C (100.4°F)• Embolic events: arterial or pulmonary emboli, conjunctival hemorrhage,retinal hemorrhage, splinter hemorrhage, intracranial hemorrhage,mycotic aneurysm• Immunologic phenomenon: Osler nodes, glomerulonephritis, positiverheumatoid factor• Positive blood cultures that don’t meet criteria above OR serologicevidence of active infection with an organism known to causeendocarditis BUT single positive cultures for coagulase-negativestaphylococci are NOT considered even a minor criterionReferences:Oral therapy: Am J Med 1996; 101:68-76.Short course therapy: Ann Intern Med 1994; 121:873-6.Duke criteria: Clin Infect Dis 2000; 30:633-8.AHA Scientific Statement on Infective Endocardits: Circulation 2005; 111(23):e394-434.TEE in S. aureusbacteremia: J Am Coll Cardiol 1997; 30: 1072-8.52Meningitis – Empiric treatmentsnoticTREATMENTef• ANTIBIOTICS SHOULD BE STARTED AS SOON AS THEn iPOSSIBILITY OF BACTERIAL MENINGITIS BECOMES EVIDENT,metIDEALLY WITHIN 30 MINUTES.sy• DO NOT WAIT FOR CT SCAN OR LP RESULTS. IF LP MUST BEs sDELAYED, GET BLOOD CULTURES AND START THERAPY.uov• Adjust therapy once pathogen and susceptibilities are known.er• Some advocate penicillin desensitization for pathogen-specific therapyn alin patients with severe allergies (p. 118).trn• Antibiotic doses are higher for CNS infections (p. 57).eC• Infectious Diseases consultation is advised for all CNS infections, 7.particularly those in which the preferred antibiotic cannot be used or in5which the organism is resistant to usual therapy.Empiric therapyHostPathogensPreferred AbxAlternative for seriousPCN allergy (IDconsultrecommended) Immunocompetent*,S. pneumo, N.Vancomycin PLUSChloramphenicolage < 50mening, H. influenzaeCeftriaxonePLUSVancomycinImmunocompetent*,S. pneumo, Listeria,Vancomycin PLUSChloramphenicolage > 50H. influenzae, Ceftriaxone PLUSPLUSVancomycinN. mening, Group BAmpicillinPLUSTMP/SMXstreptococci Immuno-S. pneumo, N.Vancomycin PLUSVancomycin PLUScompromised*+mening, H. influenzae,Cefepime PLUSTMP/SMX PLUSListeria,AmpicillinCiprofloxacin(Gram-negatives)Post neurosurgery or S. pneumo(if CSFVancomycin PLUSVancomycin PLUSpenetrating headleak), H. influenzae,CefepimeCiprofloxacintraumaStaphylococci,Gram-negativesInfected shuntS. aureus,coagulase-Vancomycin PLUSVancomycin PLUSnegative staphylococci,CefepimeCiprofloxacinGram-negatives (rare)+Immunocompromised is defined as HIV infection or AIDS, receiving immunosuppressivetherapy, or after transplantation. In patients with HIV infection, nonbacterial causes ofmeningitis must be considered, particularly cryptococcal meningitis.* Use of Dexamethasone• Addition of dexamethasone is recommended in all adult patients withsuspected pneumococcal meningitis (note that this will be most adultpatients).• Dose: 0.15 mg/kg IV Q6H for 2–4 days• The first dose must be administered 10–20 minutes before orconcomitant with the first dose of antibiotics.53sn• Administration of antibiotics should not be delayed to giveoticdexamethasone.ef• Dexamethasone should not be given to patients who have alreadyn imstarted antibiotics.e• Continue dexamethasone only if the CSF gram stain shows Gram-tsypositive diplococci or if blood or CSF grows S. pneumoniaes suovPathogen-specific therapyernPathogensPreferredAlternative for serious alPCN allergy (ID consulttrrecommended)neS. pneumoPCN MIC ≤0.06Penicillin OR CeftriaxoneVancomycin ORC µg/ml AND/OR CeftriaxoneChloramphenicol*7.MIC <0.5 µg/ml 5S. pneumoPCN MIC >0.1–1Ceftriaxone Moxifloxacin OR Linezolidµg/ml AND Ceftriaxone MIC<1 µg/ml (ID consultrecommended)S. pneumoPCN MIC > 1Ceftriaxone PLUSVancomycinMoxifloxacin OR Linezolidµg/ml AND/OR CeftriaxonePLUSRifampinMIC ≥1 µg/ml (ID consultrecommended)N. meningitidisPCNPenicillin OR Ceftriaxone+Chloramphenicol* susceptible (MIC < 0.1)H. fluAmpicillin OR CeftriaxoneChloramphenicol* ORNon β-lactamase producerCiprofloxacin H. flu Ceftriaxone Chloramphenicol* ORβ-lactamase producerCiprofloxacin ListeriaAmpicillin ±Gentamicin‡TMP/SMX P. aeruginosa(ID consultCefepime OR MeropenemAny 2 of the following:recommended)Ciprofloxacin, Tobramycin‡,Aztreonam E. coliand otherCeftriaxone ±CiprofloxacinAztreonam OR CiprofloxacinEnterobacteriaceaeOR TMP/SMXS. aureus–MSSAOxacillinVancomycinS. aureus–MRSA VancomycinCoagulase-negativeOxacillinVancomycinstaphylococci if Oxacillin MIC ≤0.25Coagulase-negativeVancomycinstaphylococci Oxacillin MIC > 0.25EnterococcusAmpicillin PLUSGentamicin‡Vancomycin PLUSGentamicin‡Candida speciesAmphotericin BCryptococcusPreferred: Amphotericin B+/- FlucytosineAlternative: Fluconazole* Consider penicillin desensitization+ Must give Ciprofloxacin 500 mg once to eradicate carrier state if PCN used as treatment‡ Administer aminoglycosides systemically, not intrathecally54sTREATMENT NOTESnotiIndications for head CT prior to LPcef• History of CNS diseases (mass lesion, CVA)n i• New-onset seizure (≤1 week)met• Papilledemasy• Altered consciousnesss s• Focal neurologic deficituovDurationern • STOP treatment if LP culture obtained prior to antibiotic therapy isalnegative at 48 hours OR no PMNs on cell counttrne• S. pneumoniae: 10–14 daysC • N. meningitidis: 7 days7.5• Listeria: 21 days• H. influenzae: 7 days• Gram-negative bacilli: 21 daysAdjunctive therapy• Consider intracranial pressure monitoring in patients with impairedmental status.Encephalitis• Herpes viruses (HSV, VZV) remain the predominant causes of treatableencephalitis.• CSF PCRs are rapid diagnostic tests and appear quite sensitive andspecific.• Have low threshold to treat if suspected as untreated mortalityexceeds 70%.• Treatment: Acyclovir 10 mg/kg IV Q8H for 14–21 days55snoBrain abscessticefn• Empiric treatment is guided by suspected source and underlying imcondition. While therapy should be adjusted based on culture results,etsanaerobic coverage should ALWAYS continue even if none are grown.ys suoSource/ ConditionPathogensPreferredAlternative forvserious PCN allergyer(ID consultn recommended)alUnknown S. aureus,Vancomycin PLUSVancomycin PLUStrnStreptococci, Gram-Ceftriaxone PLUSCiprofloxacin PLUSeCnegatives, AnaerobesMetronidazoleMetronidazole 7Sinusitis Streptococci (incl. [Penicillin ORVancomycin PLUS.5S. pneumoniae),Ceftriaxone] PLUSMetronidazoleAnaerobesMetronidazoleChronic otitisGram-negatives,Cefepime PLUSAztreonam PLUSStreptococciMetronidazoleMetronidazole PLUSAnaerobes VancomycinPost neurosurgeryStaphylococci, GramVancomycin PLUSVancomycin PLUSnegativesCefepimeCiprofloxacinCyanotic heartStreptococci (esp. Penicillin ORVancomycin diseaseS. viridans)CeftriaxoneReferences:IDSA Guidelines for Bacterial Meningitis: Clin Infect Dis 2004;39:1267.Dexamethasone in adults with bacterial meningitis: N Eng J Med 2002;347:1549.CNS shunt infectionDiagnosis• Culture of cerebrospinal fluid remains the mainstay of diagnosis.Clinical symptoms may be mild and/or non-specific, and CSFchemistries and leukocyte counts may be normal. Empiric Therapy• Vancomycin (see dosing section, p. 138) PLUSCefepime 2 g IV Q8HOR• PCN Allergy: Vancomycin (see dosing section, p. 138) PLUSCiprofloxacin 400 mg IV Q8HTREATMENT NOTES• ID consult recommended for assistance with timing of shuntreplacement and length of the antibiotic therapy.• Removal of all components of the infected shunt with externalventricular drainage or intermittent ventricular taps in combination withthe appropriate intravenous antibiotic therapy leads to the highesteffective cure rates. Success rates are substantially lower when theinfected shunt components are not removed. 56• The role of intraventricular antibiotics is controversial, and generally limitedsnto refractory cases or cases in which shunt removal is not possible.otiIntraventricular injection should be administered only by experiencedcefphysicians.n imReferences:etIDSA Guidelines for the Management of Bacterial Meningitis: Clin Infect Dis 2004;39:1267.syTherapy in cerebrospinal fluid shunt infection. Neurosurgery 1980;7:459.s suoAntimicrobial doses for CNS infections – normalverrenal functionn altrAntibioticsne• Aminoglycosides: see section on “Traditional dosing ofC aminoglycosides” (p. 134)7.5• Ampicillin: 2 g IV Q4H • Aztreonam: 2 g IV Q6H• Ceftriaxone: 2 g IV Q12H• Cefepime: 2 g IV Q8H• Chloramphenicol: 1000–1500 mg IV Q6H (reduce dose for hepaticdysfunction)• Ciprofloxacin: 400 mg IV Q8H (based on limited data)• Moxifloxacin 400 mg IV Q24H• Meropenem 2 g IV Q8H• Metronidazole: 500 mg IV Q6H• Oxacillin: 2 gm IV Q4H• Penicillin: 4 million units IV Q4H (24 million units per day)• Rifampin: 600 mg IV Q12–24H• TMP/SMX: 5 mg/kg (TMP component) IV Q6H• Vancomycin: load with 25–35 mg/kg, then 15–20 mg/kg Q8–12H(minimum 1 g Q12H)• Vancomycin should be administered to maintain serum troughconcentrations close to 20 mcg/mL.Antifungals• Amphotericin 0.7–1 mg/kg IV Q24H• AmBisome®5 mg/kg IV Q24H• Flucytosine 25 mg/kg PO Q6HIntraventricular antibiotics (ID consult recommended)• Amikacin 30 mg Q24H (contains preservative)• Gentamicin 5 mg Q24H• Tobramycin 5 mg Q24H• Vancomycin 20 mg Q24H57snoPelvic inflammatory diseaseticefn• Includes salpingitis, tubo-ovarian abscess and pelvic peritonitis. ic• For treatment of post-operative peritonitis or wound infection,iogsee p. 32 and p. 84.olcenTREATMENTyG 8Patient not severely ill.5• Cefotetan 2 g IV Q12H PLUSDoxycycline* 100 mg PO BID OR• PCN allergy (preferred): Clindamycin 600-900 mg IV Q8H PLUSGentamicin (see dosing section or OB protocol) OR• PCN allergy†: Moxifloxacin 400 mg PO ±Metronidazole 500 mg POBID for 14 daysPatient severely ill• Piperacillin/tazobactam 3.375 g IV Q6H PLUSDoxycycline* 100 mgPO BID for 14 days OR• PCN allergy†: Moxifloxacin 400 mg IV Q24H PLUSMetronidazole500mg IV Q8H for 14 daysStep-down therapy once patient is afebrile• Preferred: Doxycycline 100 mg PO BID ±[Clindamycin 450 mg PO QIDORMetronidazole 500 mg PO BID] to complete 14 days totalOR• Moxifloxacin†400 mg PO ±Metronidazole 500 mg PO BID tocomplete 14 days total* Azithromycin 500 mg IV once, then 250 mg PO daily x 6 days can be used in the caseof Doxycycline contraindication or intolerance†Given CDC recommendations to avoid use of fluoroquinolones for N. gonorrhoeaebecause of increased resistance, this regimen should be considered only if otherregimens are contraindicated. Rates of resistance in Baltimore City are ~5%.TREATMENT NOTESMicrobiology:N. gonorrhoeae, C. trachomatis, Gardnerella spp,Ureaplasma urealyticum,Anaerobes (Prevotella spp., B. fragilis), Gram-negative rods, StreptococciTreatment of partners• All women diagnosed with acute PID should be offered HIV testing.• Male partners of women who have PID caused by C. trachomatisand/or N. gonorrhoeaeoften are asymptomatic.58• Sex partners (male or female) of patients who have PID should besnexamined and treated empirically for C. trachomatisand N.otigonorrhoeaeif they have had sexual contact with the patient during thecef60 days preceding onset of symptoms in the patient, regardless of then ipathogens isolated from the patient.ciogolEndomyometritiscenyGTREATMENT 8.• Same as for PID but no need for addition of Doxycycline/Azithromycin5Duration• Treat until patient afebrile for 24–48 hoursUncomplicated gonococcal urethritis, cervicitis, proctitisTREATMENT• Ceftriaxone 125 mg IM onceOR• Cefpodoxime 400 mg PO onceOR• Cefixime 400 mg PO onceOR• Severe PCN allergy ONLY: Ciprofloxacin 500 mg PO once (The patientmust return for a test of cure if this regimen is used given emergenceof fluoroquinolone resistance among N. gonorrhoeaeisolates.)TREATMENT NOTES• Patients should also be treated for C. trachomatiswith Doxycycline100 mg PO BID for 7 days OR Azithromycin 1 g PO once. References:Sexually transmitted diseases treatment guidelines: CDC 2006. 59snoSeptic pelvic thrombophlebitisticefnBlood cultures will be positive in the vast majority of cases. Thus, ictreatment should be tailored to the culture results.iogolTREATMENTcenFor patients not already on antibioticsyG • Cefotetan 2 g IV Q12H8.5OR• Ceftriaxone 1 g IV Q24H PLUSMetronidazole 500 mg IV Q8HOR• PCN allergy: [Ciprofloxacin 400 mg IV OR500 mg PO Q12H] PLUSMetronidazole 500 mg IV/PO Q8HIf patient has already been on broad-spectrum antibiotics• Piperacillin/tazobactam 3.375 g IV Q6HSpecial considerations in pelvic thrombophlebitis• Addition of heparin is controversial. Consider if febrile after 72 hourson antibiotics• Surgery may be needed for refractory casesTREATMENT NOTESMicrobiology:Anaerobes, Streptococci, EnterobacteriaceaeDiagnosis• Persistent bacteremia is a major clue to the diagnosis.• Pelvic thrombophlebitis is generally associated with pregnancy or GYNprocedures.• CT scan is helpful for diagnosis.60COPD exacerbations snotiUncomplicatedce• Patient presenting with increased cough, sputum volume, sputumfn ipurulence, and dyspnea relative to baseline and none of the riskyfactors for complicated exacerbation. arno• Doxycycline 100 mg PO BIDmORulP • TMP/SMX 1 DS tab PO BID9.OR5• Amoxicillin 500 mg PO TID (see treatment notes below) Complicated • Patient presenting with increased cough, sputum volume, sputumpurulence, and dyspnea relative to baseline and at least one of thefollowing: FEV1< 50% predicted, more than 4 exacerbations in last 12months, significant coronary artery disease or heart failure, use ofhome oxygen, chronic oral steroid use, or antibiotic use in the pastthree months. • Azithromycin 500 mg PO/IV Q24HOR• Amoxicillin/clavulanate 875 mg PO BIDOR• Cefuroxime 750 mg IV Q8HTREATMENT NOTESMicrobiology• Predominantly H. influenzae, M. catarrhalis,S. pneumoniae• Gram-negative enteric bacilli suspected only in complicated patients Management • At JHH 25% of H. influenzaeare resistant to Amoxicillin; most M.catarrhalisisolates are beta-lactamase producers and resistant toAmoxicillin.• Patients failing therapy should have sputum Gram-stain and culture. • Empiric use of fluoroquinolones is discouraged and should only beconsidered if past or present microbiologic evidence indicates infectionwith a pathogen(s) that is resistant to standard therapy (e.g.Pseudomonas spp., Enterobacteriaceae). • IV antibiotics should only be used if the patient cannot tolerate POantibiotics. • Antibiotics are not indicated for asthma flares in the absence ofpneumonia.References:American College of Physicians Position Paper: Ann Intern Med 2001; 134:600.Canadian guidelines: Can Respir J. 2003; 10, Suppl B:3B.61snoCommunity-acquired pneumonia in ticehospitalized patientsfn iyTREATMENTarnoEmpiric Treatment – patient NOT in the ICUm• Ceftriaxone 1 g IV Q24H PLUSAzithromycin 500 mg IV/PO once daily ulPOR 9.• Moxifloxacin 400 mg IV/PO Q24H 5In non-critically ill patients, consider switch to oral agentsas soon aspatient is clinically improving and eating (see next page for oral optionsand doses).Empiric treatment – patient in the ICUNot at risk for infection with Pseudomonas (see risks on next page)• Ceftriaxone 1 g IV Q24H PLUSAzithromycin 500 mg IV Q24H OR• PCN allergy: Moxifloxacin 400 mg IV Q24H At risk for infection with Pseudomonas (see risks on next page)• Piperacillin/tazobactam 4.5 g IV Q6H PLUSAzithromycin 500 mg IVQ24H (preferred if Pseudomonasmost likely)OR• Cefepime 1 g IV Q8H PLUSAzithromycin 500 mg IV Q24H (preferred ifS. pneumoniaemost likely)OR• Severe PCN allergy: Moxifloxacin 400 mg IV Q24H PLUSAztreonam2g IV Q8H• Sputum gram stain may help determine if Pseudomonasis present. • Narrow coverage ([Ceftriaxone PLUSAzithromycin] OR Moxifloxacin)if Pseudomonasis NOT present on culture at 48 hours.• The benefits of combination therapy in the treatment of Pseudomonasare not well documented; if it is desired, then consider giving it for thefirst 5 days of therapy. Please see the section on “Combination therapyof Gram-negative bacterial infections” (p. 120).62Risks for Pseudomonassn• Prolonged hospital or long-term care facility stay (≥ 5 days)oti• Structural disease of lung (e.g., CF, bronchiectasis)cef• Steroid Rx (>10 mg prednisone/day)n i• Broad-spectrum abx for >7 days in past monthyar• AIDS (CD4 < 50)no• Granulocytopenia (ANC < 500)mulP Other causes of pneumonia9.5• Suspected aspiration:additional empiric coverage for aspiration isjustified only in classic aspiration syndromes suggested by loss ofconsciousness (overdose, seizure) PLUSgingival disease oresophogeal motility disorder. Ceftriaxone, Cefepime, and Moxifloxacinhave adequate activity against most oral anaerobes. For classicaspiration, Clindamycin 600 mg IV Q8H can be added to regimens notcontaining Piperacillin/tazobactam. • Community-acquired MRSA:Necrotizing pneumonia with cavitation inabsence of risk factors for aspiration listed above is concerning for CA-MRSA pneumonia, particularly if associated with a preceding orconcomitant influenza-like illness. In these cases, Linezolid 600 mgIV/PO Q12H can be added while awaiting culture data. Infectiousdiseases consult is strongly recommended. Use of Linezolidmonotherapy for MRSA bacteremia, even if associated with apulmonary source, is not recommended. In the absence of necrotizingpneumonia with cavitation, empiric coverage for CA-MRSA can bedeferred until sputum and blood culture results return given their highdiagnostic yield for CA-MRSA. Pathogen-specific treatments and duration• Susceptibility results should be considered when choosing an agent.• S. pneumoniae:IV: Penicillin G OR Cefuroxime OR Ceftriaxone; PO:Amoxicillin OR Cefpodoxime OR Azithromycin. Treatment for 5–10 daysbased on clinical stability. Moxifloxacin should not be used routinely asstep-down therapy for pneumococcal pneumonia if the organism issusceptible to beta-lactams.• L. pneumophila:Azithromycin for 7–10 days OR Moxifloxacin for 10–21 days.• H. influenzae:Doxycycline OR Amoxicillin/clavulanate OR Cefuroximeare preferred. Other options include Ceftriaxone OR Cefpodoxime ORMoxifloxacin. Treat for 5–10 days.• B. anthracisor pneumonic plague or tularemia (get ID consult, 3-8026;see p. 130).63snEmpiric step-down therapy oticIn absence of microbiologic data, oral options may be selected based onefinitial regimen:n iyInitialStep-downStep-downarn(preferred)(alternate)omCeftriaxone PLUSAzithromycinAzithromycinDoxycyclineulPMoxifloxacinMoxifloxacinAzithromycin OR 9Doxycycline.5Doses of oral agentsOral AgentDoseDuration*Amoxicillin1 g POthree times daily5–10Amoxicillin/clavulanateXR†2 g PO twice daily5–10Azithromycin500 mg PO once daily5‡Cefixime (suspension)400 mg PO once daily5–10Cefpodoxime200 mg PO twice daily5–10Cefuroxime axetil500 mg PO twice daily5–10Doxycycline100 mg POtwice daily5–10Moxifloxacin 400 mg POonce daily5–7*Treat for a minimum of 5 days (include therapy before oral switch). Therapy can be stoppedafter the patient is afebrile for 48–72 hours and has no more than one of the followingsigns and symptoms: HR > 100 beats/min, RR > 24 breaths/min, BP < 90 mmHg, 02sat< 90%, altered mental status. Therapy >5 days without a clinical reason should be avoided.†Preferred for step-down therapy of aspiration pneumonia‡Due to long half-lifeTREATMENT NOTESDiagnosis• Immunocompetent patients MUST have a chest X-ray infiltrate to meetdiagnostic criteria for pneumonia.• Sputum and blood cultures should be sent on all patients admitted to thehospital BEFORE antibiotics are given.• The legionella urine antigen is the test of choice for diagnosing legionellainfection. However, this test detects only L. pneumophilaserogroup 1,which is responsible for 70–80% of infections.Resolution of symptoms• Cough and chest X-ray abnormalities may take 4–6 weeks to improve.There is NO need to extend antibiotics if the patient is doing well otherwise(e.g., no fever).Other considerations• Consider Influenza during season (November through March) and test andtreat appropriately (see p. 71). • Consider anthrax infection in pneumonia patients with widened mediastinumon chest X-ray. Consult ID (3-8026) for diagnostic recommendations.References:IDSA/ATS Consensus Guidelines for CAP: Clin Infect Dis 2007;44:S27.64Healthcare-acquired pneumonia sno(NOT ventilator-associated)ticefnNOTE:If the patient is on antibiotic therapy or has recently been on iyantibiotic therapy, choose an agent from a different class.arnoTREATMENTmulEmpiric treatmentP 9No risk factors for infection with Pseudomonas (see risks below).5• Ceftriaxone* 1 g Q24HOR• Moxifloxacin 400 mg IV/PO Q24HAt risk for infection with Pseudomonas (see risks below)• Piperacillin/tazobactam* 4.5 g IV Q6HNOTE:lower dose to Piperacillin/tazobactam 3.375 g IV Q6H ifPseudomonasis NOT recoveredOR• Cefepime* 1g IV Q8HOR• PCN allergy: Ciprofloxacin 400 mg IV Q8H PLUSClindamycin 600 mgIV Q8H* IF the patient is on immunosuppressive medications or is neutropenic,ADD Azithromycin 500 mg IV/PO Q24H to cover LegionellaRisk factors for Pseudomonas infection:• Prolonged hospital or long-term care facility stay (≥5 days) • Steroid use (> 10 mg prednisone per day)• Broad spectrum antibiotics for > 7 days in past month• Structural lung disease• AIDS (CD4 < 50)• Granulocytopenia (ANC < 500)TREATMENT NOTESMicrobiology• Gram-negative rods or Enterobacteriaceae (e.g. Klebsiella, E.coli, Serratia)• Anaerobes• Legionella• S. aureus(MRSA and MSSA)• PseudomonasIF risk factors present (see above)• Enterococci and candida species are often isolated from the sputum inhospitalized patients. In general, they should be considered to becolonizing organisms and should not be treated with antimicrobials.65snAntimicrobial management of “aspiration events”oti• Prophylactic antibiotics ARE NOT recommended for patients who arecefat increased risk for aspiration.n i• Immediate treatment is indicated for patients who have small-bowelyrobstructions or are on acid suppression therapy given the increasedanorisk of gastric colonization.m• Antibiotic treatment of patients who develop fever, leukocytosis andulPinfiltrates in the 1st 48 hours after an aspiration is likely unnecessary 9since most aspiration pneumonias are chemical and antibiotic.5treatment may only select for more resistant organisms. • Treatment IS recommended for patients who have symptoms for morethan 48 hours or who are severely ill.References:Aspiration pneumonitis and aspiration pneumonia: N Engl J Med 2001;344(9):665.ATS/IDSA Guidelines for HAP/VAP: AJRCCM 2005;171:388.Ventilator-associated pneumonia (VAP)• Sputum cultures should be obtained PRIOR TO STARTING ORCHANGING ANTIBIOTICSby endotracheal suction or invasivetechniques. ET suction appears just as sensitive but less specific thaninvasive methods.• Empiric treatment MUST be narrowed as soon as sputumculture results are known.• If the patient is on antibiotic therapy or has recently been on antibiotictherapy, choose an agent from a different class.Optimal treatment can likely be based on severity of illness asdetermined by the Clinical Pulmonary Infection Score (CPIS).Calculating the Clinical Pulmonary Infection Score (CPIS)0 points1 points2 pointsTemperature (°C)36.5 to 38.438.5 to 38.9Peripheral WBC4,000 – 11,000< 4,000 or ≤36.4 or ≥39> 11,000> 50% bands: add1 extra pointTrachealNoneNon-purulentPurulentsecretionsChest X-rayNo infiltrateDiffuse or patchyLocalized infiltratesinfiltrateProgression NoneProgressionof infiltrate from(ARDS, CHFpriorthought unlikely)radiographsCulture of ETNo growth/lightHeavy growthsuctiongrowthSame bacteria ongram stain: add 1extra pointOxygenation> 240 or ARDS(PaO2/FiO2)≤ARDS240 and no66TREATMENT snIf the CPIS is ≤6otic• VAP is unlikely.ef• In a study by Singh et al, patients with a CPIS ≤6 received 3 days of an iyfluoroquinolone which was stopped at day 3 if the CPIS remained ≤6.arThese patients had NO increase in mortality or ICU stay, but they didnodevelop fewer superinfections.m• Ciprofloxacin 400 mg IV Q12 for 3 days can be considered.ulP 9.If the CPIS is >65• Treatment MUST be narrowed based on culture results.• Vancomycin (see dosing section, p. 138) PLUS[Piperacillin/tazobactam 4.5 g IV Q6H* ORCefepime 1 g IV q8H] ±Tobramycin(see dosing section, p. 132)OR• PCN allergy: Vancomycin (see dosing section, p. 138) PLUSCiprofloxacin 400 mg IV Q8H PLUSTobramycin (see dosing section, p. 132)* This is an anti-pseudomonal dose. LOWER the dose(Piperacillin/tazobactam 3.375 g IV Q6H) if PseudomonasisNOT recoveredIf the patient is immunocompromised, consider ADDING Azithromycin500 mg Q24H to Piperacillin/tazobactam to cover LegionellaTobramycin is recommended as a second agent to broaden empiriccoverage rather than fluoroquinolones because of high rates ofresistance to fluoroquinolones in the institution. Antimicrobial therapy should be tailored once susceptibilities are known.Vancomycin should be stopped if resistant Gram-positive organisms arenot recovered. Gram-negative coverage can be reduced to a singlesusceptible agent in most cases. The benefits of combination therapy inthe treatment of Pseudomonasare not well documented; if it is desired,then consider giving it for the first 5 days of therapy. Please see thesection on “Combination therapy of Gram-negative infections” (p. 120).Duration• 8 daysif the patient has clinical improvement• If symptoms persist at 8 days consider alternative source and/orbronchoscopy with quantitative cultures• VAP associated with S. aureusbacteremia should be treated for atleast 14 days67snoTREATMENT NOTESticefMicrobiologyn iy• Staphylococcus aureus(MRSA and MSSA), Pseudomonas aeruginosa,arother Gram-negative bacilli, Legionellanom• Enterococci and candida species are often isolated from the sputum inulhospitalized patients. In general, they should be considered to beP 9colonizing organisms and should not be treated with antimicrobials..5Diagnosis• VAP is difficult to diagnose.• Bacteria in endotracheal suction may represent tracheal colonizationand NOT infection. • Quantitative cultures of BAL fluid can help distinguish betweencolonization and infection; ≥104cfu/ml is considered significantgrowth.Other considerations• Tracheal colonization of Gram-negatives and S. aureusis noteradicated even though lower airways are sterilized. Thus, post-treatment cultures in the absence of clinical deterioration (fever, risingWBC, new infiltrates, worsening ventilatory status) are notrecommended.• Inadequate initial treatment of VAP is associated with higher mortality(even if treatment is changed once culture results are known).References:ATS/IDSA Guidelines for HAP/HAV: AJRCCM 2005;171:388.Clinical response to VAP: AJRCCM 2001;163:1371-1375. VAP: Arch Intern Med 2000;160:1926-6.Mini-BAL: Chest 1998;113:412-20.CPIS score: Am Rev Respir Dis 1991;143:1121–1129. Determining course of therapy using CPIS Score: Am J Respir Crit Care Med 2000; 162:505, Intensive Care Med 2004; 30: 735–738.68Antibiotic selection and dosing for cystic snofibrosis patientsticefn• Therapy should be based on culture and susceptibility data when iyavailable; the agent with the narrowest spectrum of activity should bearnselected preferentiallyom• If possible, stop failing antibiotics when initiating new antibioticsul• High doses of antibiotics should be used to maximize lung penetrationP 9.and reduce the risk of emergence of resistance (see below)5TREATMENT NOTES FOR SPECIFIC ORGANISMS• Pseudomonas aeruginosa• Piperacillin, Cefepime, and Ceftazidime should be usedpreferentially to Meropenem to minimize the induction of resistanceto beta-lactams by Meropenem • These agents are generally combined with high-doseaminoglycosides based on in vitroevidence that there is synergyagainst Pseudomonas• For patients with penicillin allergy, Ciprofloxacin or Aztreonam canbe combined with an aminoglycoside; desensitization to beta-lactams or carbapenems should be strongly considered • In patients intolerant or resistant to aminoglycosides, Colistin canbe added• Continuous infusion of beta-lactams can be considered in somepatients; call the Antibiotic Management Program (7-4570) todiscuss • Inhaled Tobramycin and Colistin can be used as adjunctive therapy• Stenotrophomonas maltophilia• S. maltophiliaisolated from sputum usually represents colonization. • If superinfection is suspected, TMP/SMX is the first line agent. • Minocycline (if susceptible) may be used in patients who are allergicor intolerant or resistant to TMP/SMX. • Staphylococcus aureus• S. aureusisolated from sputum can indicate colonization orinfection.• Whether treating colonization with S. aureusin CF patientsimproves outcomes is an area of active research, althoughhistorically such colonization has not been successfully eradicatedwith antimicrobial therapy. If this is attempted, possible agentsinclude Dicloxacillin, Cefazolin or Cephalexin for MSSA andClindamycin, TMP/SMX, and Minocycline for MRSA. • Oxacillin is the drug of choice for MSSA pneumonia; Vancomycin orLinezolid can be used for MRSA pneumonia. 69snAntibiotic doses for cystic fibrosis infections – normal renaloticfunctionef• Ceftazidime: 2 g IV Q8H n iy• Piperacillin: 4 g IV Q4Har• Piperacillin/tazobactam: 3.375 g IV Q4Hnom• Cefepime: 2 g IV Q8Hul• Meropenem: 2 g IV Q8HP 9• Ciprofloxacin: 750 mg PO Q12H OR 400 mg IV Q8H.5• Aztreonam: 2 g IV Q8H• Ticarcillin/clavulanate: 3.1 g IV Q4H• TMP/SMX for S. maltophilia:5 mg/kg IV/PO Q8H• TMP/SMX for S. aureus:2 DS tablets PO BID• Colistin: 3-6 mg/kg/day IV divided in 3 doses • Inhaled Tobramycin (TOBI®): 300 mg Q12H• Inhaled Colistin: 75-150 mg Q12H depending on the delivery system Intravenous Tobramycin dosing and monitoring:• Loading dose: 10 mg/kg/day given over 1 hour. • Peak is recommended after first dose, 1 hour after the end of infusionwith goal of 20-30 and trough at 23 hours with goal < 1 mcg/mL. • Doses can be increased up to 12 mg/kg/day if adequate peaks arenot achieved. If trough is too low or too high, interval should bechanged.70Seasonal influenza diagnosis and managementtneDiagnosis: me• Respiratory virus testing should be considered in individuals with feveragn(T >38.0°C) and influenza-like symptoms of myalgia, arthralgia,amheadache, and/or sore throat. • Information about specific diagnostic approaches can be found on thenda HEIC web site (www.hopkinsmedicine.org/heic)ssioTreatment for inpatients: nag• Should be considered for confirmed cases with symptom onset in thei dpast 48 hours. a• Consideration can be given to treating immunocompromised patientsnzeuwho are outside of the 48 hour window, although no data exist to showflnsignificant benefit at this point. ial• Antiviral choice is dependent on the susceptibility of circulating nostrains which may vary from season to season (seesaewww.hopkinsmedicine.org/amp for current recommendations).S 01.Antiviral agents5MedicationAdult dosingSide effectsNotes OseltamivirTreatment:Common: nausea, Dose adjustment 75 mg PO twice a day vomitingneeded for GFR for 5 days<30 mL/min Prophylaxis:Severe:75 mg PO once a day hypersensitivity, neuropsychiatricZanamivirTreatment:Common: diarrhea, Should NOT be used 10 mg (2 oral inhalations) nausea, cough, in patients with twice daily for 5 days headache, and chronic underlying Prophylaxis:dizziness airway diseases10 mg (2 oral inhalations) once a day Severe: bronchospasm, hypersensitivity, (laryngeal edema, facial swelling)AmantadineTreatment/Prophylaxis:Common: nervousness, Dose adjustment100 mg PO twice a day anxiety, difficulty needed for GFR or 200 mg once dailyconcentrating, <50 mL/min lightheadedness, nausea Severe: hypersensitivity, neuropsychiatricRimantadine Treatment/Prophylaxis:Common: nervousness, Dose adjustment < 65 y/o 100 mg PO anxiety, difficulty needed for GFR twice a day concentrating, ≤10 mL/min and ≥65 y/o 100 mg PO lightheadedness, severe hepatic once daily nauseadysfunction Severe: hypersensitivity, neuropsychiatric71tneInfection Control: m• All individuals with suspected influenza infection should be placed oneagdroplet precautions. A private room is required, unless patients arenacohorted. When outside of their room (i.e. during transport) patientsm should wear a mask.nd• All health care workers should receive the influenza vaccine yearly.a s• Personnel with direct patient care or working in clinical areas who havesionot received the influenza vaccine are required to wear a mask whennwithin 3 feet of a patient.ag•Employees who are febrile or have flu-like symptoms must stay home. diaIf they become sick while at work, they must go to Occupational HealthnzeServices.ufln• Employees who have cold symptoms, such as cough and runny nose, ialWITHOUT fever should wear a surgical mask during patient contact.no• If an unvaccinated HCW is exposed to a patient with documentedsainfluenza who was not on Droplet Precautions, notify HEIC and calleS Occupational Health (OH) immediately. OH will decide whether to01recommend post-exposure prophylaxis..5Notes: • These recommendations are meant to apply to inpatient care ofpatients with seasonal influenza.• Recommendations on diagnosis and management of novel influenzastrains will be provided by Antibiotic Management and HEIC ascircumstances arise and may vary from those listed here.72Tuberculosis (TB) InfectionnoticefDefinitionsni)Acid fast bacilli (AFB)Bacteria including MycobacteriumBT(tuberculosisand non-tuberculous smycobacteria (NTM) that are detectedsioin clinical specimens by directulcmicroscopy using an acid-fast stainer• Negative AFB smear does not ruleTub out active TB; cultures may yield11.results after 6–8 weeks5Tuberculin skin test (TST)Intradermal injection of purified proteinderivative (PPD) and measurement ofinduration diameter in 48–72 hours fordiagnosis of latent TB infection (alsopositive in most active TB cases).Criteria for a positive test are:• ≥5 mm – high risk of developingactive TB (e.g. HIV infection, closecontact of TB case,immunocompromised)• ≥10 mm – other risk factors forTB infection (HCW, IDU, DM)• ≥15 mm – no risk factors for TB Latent TB infection (LTBI)Previous infection with TB that hasbeen contained by the host immuneresponse• Patients may have a positive TST orsuggestive radiographic findingssuch as calcified granulomata orminimal apical scarring, but do nothave symptoms of active TBdisease• Not infectious and does not requireisolationActive TB diseaseActive replication of M. tuberculosiscausing pulmonary or extrapulmonarysymptoms and/or signs.• Confirmed by positive AFB smear,MTD test or culture• Requires airborne isolation73noWhen to suspect active TB diseaseticefHigh-risk individualsni• Recent exposure to a person with known TB; history of a positive TST;)BTHIV infection; injection or non-injection drug use; foreign birth or( sresidence in a region in which TB incidence is high; residents andsioemployees of high-risk congregate settings (e.g. prisons); membershipulcin a medically underserved, low-income population; anti-TNF alphaertherapyTub 1Clinical syndromes1.• Cough of ≥2 wk duration, with at least one additional symptom,5including fever, night sweats, weight loss, or hemoptysis• Any unexplained respiratory illness of ≥2 wk duration in a patient athigh risk for TB• Any patient with HIV infection and unexplained cough and fever • Any patient on anti-TNF alpha therapy with unexplained fever• Community-acquired pneumonia which has not improved after 7 daysof appropriate treatment • Incidental findings on chest radiograph suggestive of TB (even ifsymptoms are minimal or absent) in a patient at high risk for TBRadiographic findings• Primary TB (often unrecognized): Can resemble CAP and involve anylobes; hilar adenopathy, pleural effusions are common; cavitation isuncommon. Findings often resolve after 1–2 months. These arecommon findings in patients with advanced HIV infection and TB.• Reactivation TB: Infiltrates with or without cavitation in the upper lobesor the superior segments of the lower lobes; hilar adenopathy isvariable; CT scan may have “tree-in-bud” appearance.Diagnosis• Patients with characteristic syndromes and radiographic findingsshould have expectorated sputum obtained for AFB smear and culture.• Sensitivity of AFB smear on expectorated sputum is 50–70%; it islower in HIV+ patients. Morning expectorated sputum, induced sputum,bronchoscopy have higher sensitivity. AFB culture of lower respiratorytract specimens is considered the gold standard. • AFB smear and culture should be obtained regardless of CXR findingsin patients with high clinical suspicion, HIV infection or otherimmunocompromised states. CXR is normal in approximately 10% ofHIV-infected patients with pulmonary TB.Infection prevention and control precautionsAirborne precautions are required in the following cases:• Suspicion of disease sufficiently high to warrant obtaining sputum AFBsmear/culture as described above74• Positive AFB smear or culture until diagnosis of TB vs. NTM isnoconfirmedtic• Known active pulmonary or laryngeal TB (if patient is currently on TBefntreatment, consult with HEIC and patient’s local health department toi)obtain treatment history in order to determine if infectious at the timeBT( of current hospitalization; in meantime airborne precautions aressirequired) oulcerAlgorithm when active TB is suspectedTub 11AIRBORNE PRECAUTIONS .5IN NEGATIVE PRESSURE ROOMCollect specimen(s) for AFB smear and cultureExpectorated sputum (2 required)*Induced sputum or bronchoscopySmearSmearSmearpositive negative positive Mycobacterium MTD Obtain 2nd Smear Tuberculosis negativespecimen*negativeDirect Test (MTD) automatically performedSmearpositive If pt highly suspected for TB, await culture result and continue isolation. Otherwise, MTD test CALL HEIC 5-8384 to MTD performedDISCONTINUE ISOLATION positiveMTDMTDpositivenegativeContinue isolation until at least 14 days of therapy AND clinical improvement CALL HEICAND 3 consecutive negative 5-8384 TOsmears (Call HEIC for DISCONTINUE approval to D/C isolation on ISOLATIONsmear positive patient.) *One expectorated sputum must be a first morning specimen; samples should be collected at least 8 hours apart.75noTREATMENTticefActive TBni• ID consult is strongly recommended )BT• Therapy should be initiated for patients with positive AFB smear and( sclinical findings consistent with active TB.sio• Therapy should be considered for patients with negative AFB smearsulcwhen suspicion of TB is high and no alternate diagnosis exists. Multipleerbspecimens should be obtained for culture prior to treatment. Tu• Four drugs are necessary for initial phase (2 months). 11• Isoniazid (INH) 300* mg (5 mg/kg) PO daily .5• Rifampin (RIF) 600* mg (10 mg/kg) PO daily• Pyrazinamide (PZA) 1000 mg PO daily (40–55 kg) OR 1500 mg POdaily (56–75 kg) OR 2000* mg PO daily (76–90 kg) • Ethambutol (EMB) 800 mg PO daily (40–55 kg) OR 1200 mg POdaily (56–75 kg) OR 1600* mg PO daily (76–90 kg) *Max dose regardless of weight. • Pyridoxine 25 mg PO daily is recommended to prevent INH associatedperipheral neuropathy in patients with HIV, malnutrition, alcohol abuse,diabetes mellitus, renal failure or in pregnant or breastfeeding women. Latent TB• Treatment for latent tuberculosis should not be started in the hospitalsetting without a clear follow-up plan. Drug toxicity and monitoring• Isoniazid: asymptomatic elevation in hepatic enzymes, serious and fatalhepatitis, peripheral neurotoxicity • Rifampin: orange discoloration of body fluids, hepatotoxicity, pruritiswith or without rash • Pyrazinamide: hepatotoxicity, nongouty polyarthralgia, asymptomatichyperuricemia, acute gouty arthritis • Ethambutol: retrobulbar and peripheral neuritis •Monitoring: baseline hepatic transaminases, bilirubin, alkalinephosphatase, creatinine and CBC are recommended for all adultsinitiating TB treatment. Monthly hepatic panel is recommended forpatients with baseline abnormalities, history of liver disease or viralhepatitis, chronic alcohol consumption, HIV, IVDU, pregnancy orimmediate post-partum state or those taking other potentiallyhepatotoxic medications. Therapy should be discontinued immediatelyif AST and ALT are >3 times the upper limit of normal (ULN) in thepresence of jaundice or hepatitis symptoms or >5 times the ULN in theabsence of symptoms.References: ATS/IDSA/CDC Guidelines for diagnosis of TB: Am J Respir Care Med 2000;161:1376.ATS/IDSA/CDC Guidelines for treatment of TB: MMWR;52:RR-11. 76Sepsis in the ICU patient with no clear sourceecuroNOTE:Refer to specific sections of these guidelines for empirics treatment recommendations for specific sources of infectionarecl EMPIRIC TREATMENTon hCultures MUST be sent to help guide therapy.twi t• [Piperacillin/tazobactam 4.5 g IV Q6H ORCefepime 1 g IV q8H] ±neVancomycin (see dosing section, p. 138) (if at risk for MRSA) ±tiaTobramycin (see dosing section, p. 132) pUORC I• Severe PCN allergy: [Aztreonam 2 g IV Q8H ORCiprofloxacin 400 mgeht IV Q8H] PLUSTobramycin (see dosing section, p. 132) PLUSn iVancomycin (see dosing section, p. 138)ssiRisk factors for MRSAepS • Central venous catheter in place21• Other indwelling hardware .5• Known colonization with MRSA• Recent (within 3 months) or current prolonged hospitalization >2 weeks• Transfer from a nursing home or subacute facility• Injection drug useTREATMENT NOTES• For patients with renal insufficiency or aminoglycoside intolerance, abeta-lactam may be combined with a fluoroquinolone IF2 agents areneeded (see section on “double coverage” p. 120).• Potential sources (e.g., pneumonia, peritonitis, etc.) should beconsidered when selecting therapy.• Empiric therapy is ONLY appropriate while cultures are pending (72hours max).• Vancomycin should almost always be stopped if no resistant Gram-positive organisms are recovered in cultures.7778CellulitissnotiNOTE:The majority of cellulitis seen at JHH is associated withcefpurulent drainage. The most common etiology of cellulitis n iwith purulent drainage is S. aureus, although Group A streptococcieusand other streptococcal species can also present in this manner.stit-foTREATMENT s The following regimens include coverage for MSSA, MRSA andnda streptococci:nkiS Oral Regimens31.• Clindamycin 300 mg PO TID5OR• TMP/SMX 1–2 DS tab PO BID PLUSAmoxicillin 500 mg PO TID*OR• [Doxycycline 100 mg PO BID OR Minocycline 100 mg PO BID] PLUSAmoxicillin 500 mg PO TID**TMP/SMX, Doxycycline, and Minocycline have poor activity against Group Astreptococci.Parenteral regimens• Clindamycin 600 mg IV Q8H (mild disease)OR• Vancomycin (see dosing section, p. 138) (moderate to severe diseaseor nosocomial acquisition)Duration:7–10 daysTREATMENT NOTESMicrobiology• S. aureusand Streptococci (especially group A) • Rare causes of cellulitis are discussed belowManagement • Always elevate the affected extremity. Treatment failure is morecommonly due to failure to elevate than failure of antibiotics.• Improvement of erythema can take days, especially in patients withlymphedema, because dead bacteria in the skin continue to induceinflammation.• The microbiology lab routinely tests S. aureusisolates for inducibleClindamycin resistance and this testing is reflected in the reportedsusceptibility data. • Resistance to fluoroquinolones in S. aureus is common and developsquickly; >85% of MRSA isolates are resistant to fluoroquinolones.79snMonotherapy with fluoroquinolones for S. aureus infections is nototicrecommended.ef• Rifampin should NEVER be used as monotherapy because resistancen iedevelops rapidly.us• There is no evidence that Linezolid is superior to TMP/SMX,stiDoxycycline, or Clindamycin in the management of skin and skin-t-fostructure infection or osteomyelitis. Linezolid should only bes considered when the S. aureus isolate is resistant to or the patient isndaintolerant of these agents. nkiSOther causes of cellulitis in select patient populations 31• With bullae, vesicles, and ulcers after exposure to seawater or raw.5oysters, consider Vibrio vulnificus, especially in patients with liverdisease. Rare, but rapidly fatal if untreated. Treat with Ceftriaxone 1 g IV Q24H PLUSDoxycycline 100 mg PO BID. • Neutropenic, solid organ transplant, and cirrhotic patients may havecellulitis due to Gram-negative organisms. Consider expandingcoverage in these cases.• If eschar, consider angioinvasive organisms (GNR, aspergillosis, mold).ID consult is recommended. • Animal and human bites: Pasteurella multocida should be covered incat and dog bites. Treat with Amoxicillin/clavulanate 875 mg PO BIDOR Ampicillin/sulbactam 1.5–3 g IV Q6H. If PCN allergy: Moxifloxacin400 mg PO/IV Q24H.Cutaneous abscess • Incision and drainage (I&D) is the primary treatment for a cutaneousabscess.• Lesions that appear superficial can often have associated abscessformation that is not clearly appreciated without debridement of thewound or, on occasion, additional imaging.• At the time of I&D, a sample should be obtained for culture andsensitivity testing.• Most studies that have been published to date suggest that antibioticsare adjunct to I&D in the management of uncomplicated skinabscesses caused by CA-MRSA.• Indications for antimicrobial therapy in patients with cutaneousabscesses:• Severe or rapidly progressive infections• The presence of extensive associated cellulitis• Signs and symptoms of systemic illness• Diabetes or other immune suppression• Advanced age80• Location of the abscess in an area where complete drainage issndifficultoti• Lack of response to incision and drainage alonecef• Therapy should be given beforeincision and drainage in patients withn iprosthetic heart valves or other conditions placing them at high risk foreusendocarditis.stit-foTREATMENTs If antibiotic treatment is thought to be necessary, regimens are the samendaas for cellulitis above. If CA-MRSA is strongly suspected, can consider nnot adding Amoxicillin to TMP/SMX, Doxycycline, or Minocycline.kiS 31.Management of recurrent MRSA skin infections 51. Education regarding approaches to personal and handhygiene• Practice frequent hand hygiene with soap and water and/or alcoholbased hand gels, especially after touching infected skin or woundbandages. • Cover draining wounds with clean, dry bandages• Do not share personal items (e.g. razors; used towels and clothingbefore washing)• Regular bathing• Avoid all shaving • Launder clothing, sheets, towels in hottest suitable temperature• Clean all personal sporting clothing/equipment 2. Decontamination of the environment• Clean high touch areas in the bathroom with a disinfectant activeagainst S. aureusdaily (e.g. 10% dilute bleach). 3. Topical decolonization (consider if a patient has ≥2 episodesin 1 year or other household members develop infection)• Mupirocin twice daily for 5 days may be considered in patients withdocumented evidence of MRSA nasal colonization; Mupirocintherapy should be initiated after resolution of acute infection.Mupirocin should not be used in patients or patients’ familymembers who are not documented to have MRSA nasalcolonization.• Bathing or showering with chlorhexidine or hexachlorophine (ordilute bleach baths) every other day for 1 week then twice weekly;do not get these substances into ears or eyes• Systemic antibiotics are NOT recommended solely for decolonization4. Evaluation of other family members• Intra-family transmission should be assessed and if present, allmembers should participate in hygiene and decolonization81snstrategies above, starting at that same time and after the acuteoticinfection is controlled. efn iNOTE:Data on efficacy and durability of the decontamination andeudecolonization strategies described above are limited. sstiReferences:t-fTMP/SMX for MRSA: Ann Intern Med 1992;117:390-8.osManagement of CA-MRSA: http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html. nda nDiabetic foot infectionskiS 3TREATMENT1.5Treatment depends on clinical severityInfection SeverityClinical ManifestationsUninfected No purulence or inflammation*MildPresence of purulence and ≥1 signs of inflammation*and cellulitis (if present) ≤2 cm around ulcer limited toskin or superficial subcutaneous tissueModerateSame as mild PLUSat least one of the following: > 2cm of cellulitis, lymphangitic streaking, spread beneaththe superficial fascia, deep tissue abscess, gangrene,involvement of muscle, tendon, joint, or boneSevereAny of above PLUSsystemic toxicity or metabolicinstability*erythema, pain, tenderness, warmth, indurationMILD INFECTIONSOral regimens• Cephalexin 500 mg PO QIDOR• Clindamycin 300 mg PO TID (covers MRSA)OR• Amoxicillin/clavulanate 875 mg PO BIDParenteral regimens• Clindamycin 600 mg IV Q8H (covers MRSA)OR• Oxacillin 1-2 g IV Q4HOR• Cefazolin 1 g IV Q8H82sMODERATE INFECTIONSnoti• Cefotetan 1 g IV Q12HcefORn i• Ertapenem 1 g Q24HeusORsti• [Ciprofloxacin* 500 mg PO BIDOR Ciprofloxacin* 400 mg IV Q12H]t-foPLUS ONEof the following [Clindamycin 600 mg IV Q8H/300 mg POs TID OR Metronidazole 500 mg IV/PO TID]nda* BUT avoid fluoroquinolones in patients who were on them as noutpatientskiS If patient at risk for MRSA,add Vancomycin to regimens that do not31.include Clindamycin.5Risk factors for MRSA• History of colonization or infection with MRSA• Recent (within 3 months) or current prolonged hospitalization >2weeks• Transfer from a nursing home or subacute facility• Injection drug useSEVERE INFECTIONS• Pipercillin/tazobactam 4.5 g IV Q6HOR• Ciprofloxacin* 400 mg IV Q12H PLUSClindamycin 600 mg IV Q8H* BUT avoid fluoroquinolones in patients who were on them asoutpatients. If patient at risk for MRSA(see above)• Piperacillin/tazobactam 4.5 g IV Q6H PLUSVancomycin (see dosingsection, p. 138)OR• Ciprofloxacin* 400 mg IV Q12H PLUSMetronidazole 500 mg IV Q8HPLUSVancomycin (see dosing section, p. 138)* BUT avoid fluoroquinolones in patients who were on them as outpatientsTREATMENT NOTESManagement• A multidisciplinary approach to management should include woundcare consultation, assessment of vascular supply, vascular and/orgeneral surgery consultation and infectious diseases consultation. • Consider necrotizing fasciitis in patients who are severely ill.• Antibiotic therapy should be narrowed based on culture results.83snMicrobiologyotic• Cellulitis without open wound or infected ulcer, antibiotic naïve: efbeta-hemolytic streptococci, S. aureusn ie• Infected ulcer, chronic or previously treated with antibiotics: S. aureus,usbeta-hemolytic streptococci, Enterobacteriaceaesti• Exposure to soaking, whirlpool, hot tub: usually polymicrobial, mayt-foinvolve Pseudomonass • Chronic wounds with prolonged exposure to antibiotics: aerobic Gram-ndapositive cocci (GPC), diptheroids, Enterobacteriaceae, other Gram- nkinegative rods (GNR) including PseudomonasS 3• Necrosis or gangrene: mixed aerobic GPC and GNR, anaerobes1.5Diagnosis• Cultures of the ulcer base after debridement can help guide therapy.Biopsy of unexposed bone is NOT recommended. Avoid swabbing non-debrided ulcers or wound drainage.• Ulcer floor should be probed carefully. If bone can be touched with ametal probe then the patient should be treated for osteomyelitis withantibiotics in addition to surgical debridement.• Plantar fasciitis and a deep foot-space infection can be present.Consider imaging to look for deep infections. • Putrid discharge is diagnostic of the presence of anaerobes.• MRI is more sensitive and specific than other modalities for detectionof soft-tissue lesions and osteomyelitis.Duration• Duration of treatment will depend on rapidity of response and presenceof adequate blood supply.• Likely need shorter treatment with adequate surgical intervention (7–10days post-op) and longer for osteomyelitis.• Change to oral regimen when patient is stable.Reference:IDSA Guidelines: Clin Infect Dis 2004;39:885-910.Surgical-site infections (SSI)TREATMENTInfections following clean procedures(e.g. orthopedic jointreplacements, open reduction of closed fractures, vascular procedures,median sternotomy, craniotomy, breast and hernia procedures)• Oxacillin 1–2 g IV Q4HOR• Cefazolin 1 g IV Q8HOR84• PCN allergy: Clindamycin 600 mg IV Q8HsnORoti• Involvement of hardware: Vancomycin (see dosing section, p. 138)cefnException:Saphenous vein graft harvest site infections should be ietreated with Cefotetan 1 g IV Q12H OR Ertapenem 1 g IV Q24HusstiInfections following contaminated procedures(GI/GU procedures,t-foropharyngeal procedures, obstetrical and gynecology procedures)os Patients not on broad-spectrum antibiotics at time of surgery and nda not severely illnki• Cefotetan 1 g IV Q12HS 3OR1.• Ertapenem 1 g IV Q24H5OR• PCN allergy: [Ciprofloxacin 500 mg PO BID OR Ciprofloxacin 400 mg IVQ12H] PLUSClindamycin 600 mg IV Q8HPatients on broad-spectrum antibiotics at time of surgery or severely ill• Piperacillin/tazobactam 3.375 g IV Q6H ±Vancomycin (see dosing section, p. 138) (if hardware present or MRSA suspected)OR• PCN allergy: Vancomycin (see dosing section, p. 138) PLUS[Ciprofloxacin 500 mg PO BID OR Ciprofloxacin 400 mg IV Q12H]PLUSMetronidazole 500 mg IV/PO Q8HDeep fascia involvement• Treat as necrotizing fasciitis (see subsequent section)TREATMENT NOTESMicrobiology• Following clean procedures (no entry of GI/GU tracts)• Staphylococcus aureus• Streptococci, group A (especially with early onset, < 72 hours)• Coagulase-negative staphylococci• Following clean-contaminated and contaminated procedures (entry ofGI/GU tracts with or without gross contamination)• Organisms above• Gram-negative rods• Anaerobes (consider Clostridiaspp. in early-onset infection, 1–2days)• Generally, empiric use of Vancomycin is not indicated because thepercentage of SSIs caused by MRSA is low at Johns Hopkins Hospital(10–20%)85snRisk factors for MRSAotic• History of colonization or infection with MRSAef• Recent (within 3 months) or current prolonged hospitalization >2 weeksn ie• Transfer from a nursing home or subacute facilityus• Injection drug usestit-fOther management issuesos • Many advocate that ALL infected wounds be explored both to debridendand to assess depth of involvement.a n• Superficial infections may be adequately treated with debridementkiSalone. 31• Deeper infections (cellulitis, pannicullitis) need adjunctive antibiotics..5• Infections that extend to the fascia should be managed as necrotizingfasciitis.• Patients with hypotension should have their wounds explored even ifthey are unremarkable on physical exam.Serious, deep-tissue infections (necrotizing fasciitis)THESE ARE SURGICAL EMERGENCIES!ANTIBIOTICS ARE ONLY AN ADJUNCT TO PROMPTDEBRIDEMENT!ID should also be consulted (3-8026)TREATMENT (adjunct to surgery)• Vancomycin (see dosing section, p. 138) PLUS[Piperacillin/tazobactam 3.375 g IV Q6H OR Cefepime 1 g IV Q8H] PLUSClindamycin 600-900 mg IV Q8HOR• PCN allergy: Vancomycin (see dosing section, p. 138) PLUSCiprofloxacin 400 mg IV Q12H PLUSClindamycin 600-900 mg IV Q8H TREATMENT NOTESConventional nomenclature and microbiologyPyomyositis• S. aureusmost commonly• Clostridial myonecrosis – Clostridiaspp. (esp. C. perfringens)• Group A streptococcal myonecrosisFasciitis• Type 1 – Polymicrobial infections with anaerobes, streptococci andGram-negative rods (Fournier’s gangrene is a type 1 necrotizingfasciitis of the perineum)86• Type 2 – Group A streptococci predominatesn• Cases of fasciitis caused by community-associated MRSA strains haveotibeen reportedcefnDiagnosis ie• Can be difficult – gas production is not universal and is generallyussabsent in streptococcal diseases.tit-f• Maintain high index of suspicion when:os • Patients are very ill from cellulitis (hypotension, toxic appearance)nd• Pain out of proportion to physical findingsa n• Anesthesia over affected areaki• Risk factors such as diabetes, recent surgery or obesityS 3• Findings such as skin necrosis or bullae1.5• Putrid discharge with thin, “dishwater” pus• CT scan can help with diagnosis but if suspicion is moderate to high,surgical exploration is the preferred diagnostic test. DO NOT delaysurgical intervention to obtain CT.8788Bacterial urinary tract infections (UTI)snotiNOTES:ce• The diagnosis of a UTI in inpatients can be difficult. fn i• Signs and symptoms, the presence of a urinary catheter, and thetcaquality of specimen collection must be considered before initiation oftr treatment.yar• Collection of cultures in the absence of signs and symptoms should benavoided. Uri • All recommendations are for empiric treatment; narrow coverage41.based on susceptibilities.5Management of patients WITHOUT a urinary catheterNOTE: Ciprofloxacin has been removed as an empiric treatmentrecommendation for in-patients with non-catheter associated UTI at JHHdue to the low rate of E. coli susceptibility (59%). Use of Ciprofloxacincan be considered in patients with known-susceptible isolates or withnon-lactose fermenting organisms in the urine.CategoryDefinitionEmpiric treatmentAsymptomatic Positive urine cultureNo treatment unless the patient is:bacteriuria with no signs or• Pregnant symptoms• About to undergo a urologic procedure • Post renal transplant• NeutropenicAcute cystitisSigns and symptomsUncomplicated: female, no urologic abnormalities,(e.g. dysuria, urgencyno stones, no catheterfrequency, suprapubic• TMP/SMX 1 DS tab PO Q12H for 3days pain)ORAND pyuria (>5–10• Cephalexin 500 mg PO Q6H for 7days WBC/hpf ) ORAND positive urine• Nitrofurantoin (Macrobid®) 100 mg PO Q12H forculture ≥100,0005 days (do NOT use in patients with coloniesCrCl <40ml/min)Complicated: male gender, possible stones,urologic abnormalities, pregnancySame regimens as above except duration is 7–14 daysAcute Signs and symptomsPatient not severely illpyelonephritis(e.g. fever, flank pain) • Ertapenem 1 g IV Q24HAND pyuria ORAND positive urine• Ceftriaxone 1 g IV Q24Hculture ≥100,000• Duration 7–14 dayscoloniesPatient severely ill or hospitalized >48 HMany patients will have• Cefepime 1 g IV Q8H other evidence ofORupper tract disease• PCN allergy: Aztreonam 1 g IV Q8H(i.e. leukocytosis, WBC• Duration: 7–14 dayscasts, or abnormali-ties upon imaging)UrosepsisSIRS with urinary• Cefepime 1 g IV Q8Hsource of infectionOR• PCN allergy: Aztreonam 1 g IV Q8H• Duration: 7–14 days89snDIAGNOSISoticSpecimen collection: The urethral area should be cleaned with anefantiseptic cloth and the urine sample should be collected midstreamn itor obtained by fresh catheterization. Specimens collected using acadrainage bag or taken from a collection hat are not reliable andtr yshould not be sent.arnUriInterpretation of the urinalysis (U/A) and urine culture 4• Urinalysis and urine cultures must be interpreted together in1.5context of symptoms• Urinalysis/microscopy:• Dipstick• Nitrites indicate bacteria in the urine• Leukocyte esterase indicates white blood cells in the urine• Bacteria: presence of bacteria on urinalysis should beinterpreted with caution and is not generally useful• Pyuria (more sensitive than leukocyte esterase): >5–10 WBC/hpfor >27 WBC/microliterUrine cultures:• If U/A is negative for pyuria, positive cultures are likelycontamination• Positive cultures with pyuriaare defined as ≥100,000 (105)colonies. This cutoff is the most sensitive for a true UTI.Situationsin which lower colony counts < 105are significant include: patientswho are already on antibiotics at the time of culture, symptomaticyoung women, suprapubic aspiration, and men with pyuria. TREATMENT NOTES• Sterile pyuria (positive U/A, but negative urine cultures) usuallyrequires no treatment, although if the patient has receivedantibiotics, the patient may still have a UTI. If sterile pyuria persistsconsider other causes (e.g. interstitial nephritis or cystitis,fastidious organisms). • Follow-up urine cultures or U/A are only warranted for ongoingsymptoms. They should NOT be acquired routinely to monitorresponse to therapy.• See below for discussion of treatment options for VRE and renalconcentrations of antibiotics.90Management of patients WITH a urinary cathetersnoCategoryDefinitionEmpiric treatmentticAsymptomatic Positive urine cultureRemove the catheter efbacteriuriawith no signs orNo treatment unless the patient is:n isymptoms of infection• Pregnant tc• About to undergo a urologic procedure aNOTE: obtaining• Post renal transplanttr yroutine cultures in• Neutropenicarasymptomatic patientsAntibiotics do not decrease asymptomaticnis not recommended bacteriuria or prevent subsequent development ofUriUTI 4Catheter-Signs and symptoms• Remove (PREFERRED) or replace catheter in all1.associated UTI (fever with no othersymptomatic patients5(CA-UTI)source is the mostPatient stable with no evidence of upper tractcommon; patients maydisease:also have suprapubic• If catheter removed, consider observation aloneor flank pain) ORAND pyuria (>5–10• Ertapenem 1 g IV Q24HWBC/hpf)ORAND positive urine• Ceftriaxone 1 g IV Q24Hculture ≥100,000ORcolonies (see• Ciprofloxacin 500 mg PO BID or 400 mg IV Q12Hinformation below(avoid in pregnancy and in patients with priorregarding significantexposure to quinolones)colony counts)• Duration: see treatment notes belowPatient severely ill, with evidence of upper tractdisease, or hospitalized >48 H:• Cefepime 1 g IV Q8H OR• PCN allergy: Aztreonam 1 g IV Q8H• Duration: 7–14 daysDIAGNOSISSpecimen collection: urine sample should be drawn in a sterile fashionfrom fresh catheter specimen. It should be drawn from either the catheteritself or through the port designed specifically for this purpose, NOTfromthe urine collection bag. Specimen collection is critical since colonizationof the Foley bag or actual catheter is common. Symptoms: Catheterized patients often lack typical symptoms of dysuria,although fever, suprapubic pain, and flank pain may still be present.Interpretation of the urinalysis (U/A) and urine culture• Pyuria: defined as >5–10 WBC/hpf or >27 WBC/microliter. In thepresence of a catheter, pyuria or positive cultures are not always areliable indicator of infection. Lack of pyuriasuggests no activeinfection.• Positive urine culture: ≥100,000 colonies is the most specific for trueCA-UTI. Some experts state that ≥ 1,000 colonies represent significantbacteriuria; however, if this count is used, there should be a strongsuspicion of CA-UTI based on symptoms and absence of infection atanother site.91snTREATMENT NOTESotic• Remove catheter whenever possible ef• The duration of treatment has not been well studied for CA-UTI. n it• Assess the degree of illness, comorbidities, and clinical responsecato determine duration of therapy. As a general guide:tr y• If the catheter is removed and the patient is not severely ill andarnhas good response to treatment: 5–7 daysiUr• If catheter remains present or the patient is severely ill (e.g. 4urosepsis) or has pyelonephritis: 7–14 days1.5Treatment of Enterococci• Almost all E. faecalisisolates are susceptible to Amoxicillin 500 mgPO TID OR Ampicillin 1 g IV Q6H and should be treated with theseagents. For patients with PCN allergy: Nitrofurantoin ( Macrobid®) 100mg PO Q12H (do NOT use in patients with CrCl < 40 mL/min). • E. faecium (often Vancomycin resistant)• Nitrofurantoin (Macrobid®) 100 mg PO Q12H if susceptible (do NOTuse in patients with CrCl < 40 mL/min).• Tetracycline 500 mg PO Q6H if susceptible• Fosfomycin 3 g PO once (if female without catheter or catheteris removed; ask the micro lab for susceptibility)• Linezolid 600 mg PO BID OR Fosfomycin 3 g PO every 2–3 days(max 21 days) if complicated UTI or catheter can not beremoved Renal excretion/concentration of selected antibiotics Good (≥60%):aminoglycosides, Amoxicillin, Amoxicillin/clavulanate,Fosfomycin, Cefazolin, Cefepime, Cephelexin, Ciprofloxacin, Colistin,Ertapenem, Trimethoprim/sulfamethoxazole, Vancomycin,Amphotericin B, Fluconazole, FlucytosineVariable (30-60%):Cefpodoxime, Linezolid (30%), Doxycycline (29–55%), Ceftriaxone, Tetracycline (~60%) Poor (<30%):Azithromycin, Clindamycin, Moxifloxacin, Oxacillin,Tigecycline, Micafungin, Posaconazole, VoriconazoleReferences:Pyuria and urinary catheters: Arch Int Med 2000;160(5):673-77.IDSA Guidelines for treatment of uncomplicated acute bacterial cystitis andpyelonephritis in women: Clin Infect Dis 1999;29:745.European and Asian guidelines on management and prevention of CA-UTI: Int J AntimicrobAgents 2008; 31S:S68.92Resistant Gram-negative infectionssnotiPatients with infection or colonization with the resistantceorganisms listed below should be placed on CONTACTfn iprecautions (see isolation chart on p. 125)evtiExtended spectrum beta-lactamase (ESBL)-producing organismsaeg• ESBLs are enzymes that confer resistance to all penicillins,ncephalosporins, and Aztreonam.m-a• They are most commonly seen in K. pneumoniaeand K. oxytoca, Gr E. coli, and P. mirabilis, and these organisms are automaticallytnascreened by the JHH microbiology lab for the presence of ESBLs. ts• Risk factors for infection or colonization: recent hospitalization at ansieinstitution with a high rate of ESBLs, residence in a long-term careR 5facility and prolonged use of broad spectrum antibiotics.1.5Treatment:• Meropenem 1 g IV Q8H (2 g IV Q8H for CNS infections) should be usedfor ALL severe infections if the organism is susceptible.• Ertapenem 1 g IV Q24H can be used for uncomplicated UTI or softtissue infection with adequate source control if the organism issusceptible.• Ciprofloxacin or TMP/SMX can be used as alternatives to Ertapenemfor uncomplicated UTI or soft tissue infection with adequate sourcecontrol if the organism is susceptible. Nitrofurantoin may also be usedfor uncomplicated UTI if the organism is susceptible. Carbapenemase-producing Enterobacteriacae• Carbapenemases are enzymes that confer resistance to all penicillins,cephalosporins, carbapenems and Aztreonam. •Enterobacteriaceae are automatically screened by the JHHmicrobiology lab and a modified Hodge test is conducted to confirmthe presence of carbapenemases. Hodge test resultSusceptibility on panelReportingHodge test (+)ResistantReported as resistantHodge test (+)Susceptible or IntermediateMIC only without interpretation*Hodge test (-)Susceptible, Intermediate Reported as tested, no or Resistantcarbapenemase production*Infections caused by organisms that are modified-Hodge test positive in the susceptible orintermediate range may respond to extended infusions of Meropenem in combination with anaminoglycoside. Consult ID or Antibiotic Management for recommendations.93snTreatment: otic• If Hodge test (+) and Meropenem susceptible or intermediate:efMeropenem 2 g IV Q8H infused over 3 hours PLUSaminoglycoside ifn ieMIC within susceptible or intermediate range.vti• If carbapenem resistant and Colistin susceptible: Colistin 2.5 mg/kg IVaQ12H can be used for serious infections egn• Alternatives for Colistin-resistant organisms include aminoglycosidesm-aand Tigecycline (do not use either as monotherapy for bacteremia). Gr tnMulti-drug resistant (MDR) gram-negative organisms:defined asatsorganisms susceptible to NO MORE than ONE of the following antibioticsieclasses: carbapenems, aminoglycosides, fluoroquinolones, penicillins, orR 5cephalosporins. Note:susceptibility to sulfonamides, tetracyclines,1.polymixins, and Sulbactam are NOT considered in this definition5TreatmentMDR Pseudomonas aeruginosaMDR Acinetobacter baumannii/calcoaceticus complex• Anti-pseudomonal -lactam PLUS• -lactam PLUSaminoglycoside if synergy predicted aminoglycoside if synergy predicted or confirmed or confirmed OROR• Colistin (if susceptible) • Colistin (if susceptible)OR• Ampicillin/sulbactam (if susceptible) PLUSaminoglycoside (Sulbactam component has in vitroactivity against Acinetobacterspp.) OR• Tigecycline (if susceptible; for infections other thanbacteremia)*Combination therapy should be considered in severe infections.Synergy testing: • Consult ID or Antibiotic Management to request synergy testing. • If the organism is intermediate to a beta-lactam and susceptible toaminoglycosides, synergy can be assumed. • If the organism is resistant to beta-lactams and susceptible orintermediate to aminoglycosides, request synergy testing. Antibiotic doses for MDR and carbapenemase-producinginfections – normal renal function• Meropenem: 2 g IV Q8H, infuse over 3 hours • Cefepime: 2 g IV bolus loading dose over 30 minutes, then 6 g IV ascontinuous infusion over 24 hours • Ceftazidime: 2 g IV bolus loading dose over 30 minutes, then 6 g IV ascontinuous infusion over 24 hours 94• Piperacillin/tazobactam: 3.375 g IV bolus loading dose over 30snminutes, then continuous infusion 3.375 g IV Q4H infused over 4otihours OR4.5 g IV Q6H, infuse over 4 hourscef• Piperacillin: 4 g IV bolus loading dose over 30 minutes, thenn icontinuous infusion 4 g IV Q4H infused over 4 hoursevti• Colistin: 2.5 mg/kg IV Q12H (for additional information, see p. 9)aeg• Ampicillin/sulbactam: 3 g IV Q4H (for MDR A. baumannii only)n• Aminoglycosides (for dosing, see p. 132)m-• Tigecycline 100 mg IV once, then 50 mg IV Q12H (for MDR non-aGrbacteremic A. baumannii only) tnatsReferences: siESBLs and clinical outcomes. Clin Infect Dis 2006:42;S164.eRCurrent therapies for P. aeruginosa. Crit Care Clin 2008;24:261. 5MMWR: Guidance for control of infections with carbapenem – resistant or carbapemase –1.producing Enterobacteriaceaein acute care facilities; 2009, March; 58(10): 256-260.59596Candidiasis in the non-neutropenic patients tnetiaOropharyngeal disease (thrush) pcInitial treatment nie• Clotrimazole 10 mg troche 5 times a dayopOR true• Nystatin suspension 500,000 units/5mL 4 times a daynn-Recurrent or intractable diseaseon • Fluconazole 100–200 mg PO once dailyeht Duration: 5–10 daysn isNOTE: If refractory to Fluconazole consider fungal culture andsiasusceptibilitiesidindEsophageal candidiasisaC Initial treatment61.• Fluconazole 200–400 mg IV/PO once daily5Duration: 14-–21 daysRelapse• Fluconazole 400–800 mg IV/PO once dailyRefractory to Fluconazole 800 mg daily(fungal culture andsusceptibilities are recommended)• Micafungin 150 mg IV once dailyOR • Amphotericin B 0.3–0.7 mg/kg IV once dailyOR • Oral therapy: Itraconazole oral solution 200 mg dailyDuration: 14–21 daysCandiduria• Urinary catheter removal will resolve the candiduria in 40% of cases.TREATMENTAsymptomatic cystitis • Therapy not usually indicated• Consider in the following conditions (see regimens under “symptomaticcystitis”):• Neutropenic patients • Renal transplant• Urinary obstruction or abnormal GU tract• When recovered in urine prior to urologic procedures• When recovered in urine prior to surgery to implant hardware(joints, valves, etc.)97tneSymptomatic cystitistia pPreferred therapycni• Fluconazole 200 mg IV/PO once daily eopDuration:7–14 daystrueFluconazole-resistant organism suspected or confirmedn• Amphotericin B 0.3-0.6 mg/kg IV once daily n-onDuration:1–7 days eht nPyelonephritis issiNOTE:Candida pyelonephritis is usually secondary to hematogenousaispread except for patients with renal transplant or abnormalities of theurogenital tract. ndidaCPreferred therapy 61• Fluconazole 200–400 mg IV/PO once daily .5Duration:14 days Fluconazole-resistant organism suspected or confirmed • Amphotericin B 0.5–0.7 mg/kg IV once daily OR• Micafungin 100 mg IV once daily Duration:14 daysTREATMENT NOTES• Remove urinary catheter if possible.• Therapy of candiduria in the non-neutropenic, non-ICU catheterizedpatient has not been shown to be beneficial and promotes resistance.• AmBisome®, Voriconazole, Itraconazole, and Posaconazole are notrecommended due to poor penetration into the urinary tract.• Micafungin penetrates poorly in the urine, but does penetrate into renaltissue.• Amphotericin B bladder washes are not recommended.Candida vaginitisInitial Therapy• Fluconazole 150 mg PO X 1 dose OR• Miconazole 2% cream 5 g intravaginally once daily X 7 daysRecurrent(> 4 episodes/year of symptomatic infection)• Fluconazole 150 mg PO Q72H X 3 doses, then 150 mg a week X 6 months98Candidemiatne• YEAST IN A BLOOD CULTURE SHOULD NOT BE CONSIDERED AtiaCONTAMINANT. pcNOTE: Micafungin does not have activity against Cryptococcus nieopTREATMENTtrueUnspeciated candidemiann-Patients who are clinically stable and have not received prior long-termon azole therapyeht• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once daily n isPatients who are NOT clinically stable due to Candidemia or havesiareceived prior long-term azole therapydi• Micafungin 100 mg IV once daily ndiaCIf the yeast is C. albicansor C. glabratabased on PNA FISH results, 6follow the recommendations for C. albicansor C. glabratanoted below.1.5Otherwise, await speciation before modifying therapy as recommendedbelow, unless the patient becomes clinically unstable on Fluconazole.Candida albicans• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once dailyPatients who are NOT clinically stable due to Candidemia or havereceived prior long-term azole therapy• Micafungin 100 mg IV once daily Patients should be transitioned to Fluconazole once stable.Candida glabrata• Micafungin 100 mg IV once dailyOR• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once daily IFthe isolate is susceptible with MIC ≤8 mcg/mL and the patient is stable.If isolate is intermediate to Fluconazole and oral therapy is desired,consult ID. Other azoles such Voriconazole should not be used inFluconazole-resistant strains due to the same mechanism of resistance. Candida krusei• Micafungin 100 mg IV once daily Fluconazole should NEVER be used to treat infections due to C. kruseibecause the organism has intrinsic resistance to Fluconazole. Thismechanism of resistance is not shared with Voriconazole; therefore, oralVoriconazole can be used if isolate is susceptible (for dosing seeVoriconazole specific guidelines, p. 20). 99tneCandida lusitaniaetia• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once daily pcC. lusitaniaeis resistant to Amphotericin B in approximately 20% ofniecases.optrueCandida parapsilosisnn-• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once dailyon Fluconazole-intermediate isolateeh• Fluconazole 800 mg IV/PO once dailyt n iFluconazole-resistant isolatessia• Micafungin 100 mg IV once dailyidiIf the patient is not responding to Micafungin then consider changing tondaAmphotericin B. The minimum inhibitory concentrations (MICs) ofC echinocandins are higher for C. parapsilosisthan any other Candida61.spp.; this has led to concern that some infections with C. parapsilosis5may not respond well to echinocandins. Candida tropicalis• Fluconazole 800 mg IV/PO X 1 dose, then 400 mg IV/PO once dailyFluconazole-intermediate isolate• Fluconazole 800 mg IV/PO once dailyFluconazole-resistant isolate• Micafungin 100 mg IV once dailyTREATMENT NOTESAmphotericin B use in Candidemia• Amphotericin B is highly effective against all Candidaspp. except for C.lusitaniae; however, azoles and echinocandins are favored insusceptible strains over Amphotericin B products due to toxicity.Doses for Candidemia• Amphotericin B 0.7 mg/kg IV once dailyOR• AmBisome®3 mg/kg IV once daily (if patient cannot tolerateconventional Amphotericin B)Duration• 14 days following documented clearance of blood cultures and clinicalsymptoms• Patients with persistent candidemia and/or metastatic complications(e.g. endophthalmitis, endocarditis) need a longer duration of therapyand evaluation by Ophthalmology and ID. 100MicrobiologytnFluconazole susceptibilities (%) of fungal isolates in blood at JHH,eti8/2007–4/2009a pcOrganism#S (%)I (%)R (%)nieC. albicans3010000opC. glabrata35315415truC. parapsilosis1410000enC. tropicalis10801010n-oS – susceptible (MIC ≤8); I – intermediate (MIC =16-32); R – resistant (MIC ≥64)n ehNon-pharmacologic managementt n• Removal of all existing central venous catheters is highly isrecommended. sia• Patients should have blood cultures daily or every other day untildicandidemia is cleared.ndia• Patients should have an ophthalmologic examination to excludeC 6candidal endophthalmitis prior to discharge, preferably once the1.candidemia is controlled.5• Echocardiography can be considered if the patient has persistentcandidemia on appropriate therapy.Endophthalmitis• Management in conjunction with Ophthalmology• Due to poor CNS and vitreal penetration, treatment with echinocandinsis NOT recommended.Preferred therapy•Amphotericin B 1 mg/kg IV once daily ±Flucytosine 25 mg/kg PO Q6HOR• AmBisome®5 mg/kg IV once daily ±Flucytosine 25 mg/kg PO Q6HAlternate therapy• Fluconazole 400-800 mg/kg IV/PO once daily ±Flucytosine 25 mg/kgPO Q6HDuration: 4–6 weeksEndocarditisConsultation with ID and Cardiac Surgery is recommended. Surgicalvalve replacement is considered a critical component for cure. If thepatient is not a candidate for surgery then life-long Fluconazolesuppression is likely required. 101tnePreferred therapytia• Amphotericin B 1 mg/kg IV once daily pcORnie• AmBisome® 5 mg/kg IV once dailyopAlternative therapytrue• Micafungin 150 mg IV once dailynn-Duration: 6 weeks or longeron ehtNotes on antifungal susceptibility testing n• Susceptibility testing for Fluconazole, Itraconazole, Voriconazole, issiFlucytosine, and Micafungin is performed routinely on the first yeastadiisolate recovered from blood.ndi• Fluconazole and Micafungin susceptibility are reported on all isolates.aC• Susceptibility testing for conventional Amphotericin B is done routinely 6for C. lusitaniaeand C. guillermondii, and for other organisms by1.5request.• If the organism is intermediate (I) to Fluconazole, then 800 mg IV/POonce daily can be used. This choice is NOT recommended in animmunocompromised patient, in a patient who is clinically unstable dueto candidemia, in a patient with C. glabratacandidemia or in patientswith endocarditis, meningitis or endophthalmitis.• Susceptibility testing should be considered when:• Mucocutaneous candidiasis is refractory to Fluconazole• Treating osteomyelitis, meningitis, or endophthalmitis withFluconazole• Blood cultures are persistently positive on Fluconazole• Non-routine susceptibility testing can be arranged by calling themycology lab at 5-6148References:IDSA Guidelines for Treatment of Candidiasis: Clin Infect Dis 2009;48:503-535.102Fluconazole prophylaxis salobiPending further research, Fluconazole prophylaxis should becrlimited to the following settings:miti• Patients expected to remain in the SICU or WICU for ≥72 hoursna (Criteria from Hopkins SICU prophylaxis study; prophylaxis in otherctiICUs has NOT been studied and is NOT recommended).ca• Neutropenic patients undergoing bone marrow transplantation (see ylhp. 99).op• Patients who are post-op from liver or pancreas transplants. prfo eDose and routesu • ALL treatment should be PO or per feeding tube.IV prophylaxis isorfNOT recommended (based on Hopkins study). se• Fluconazole 800 mg PO load then 400 mg PO once daily. IF creatininenliclearance less than 25 mL/min, then maintenance dose is 200 mg POeonce daily.uidG 7Duration1.5• For SICU and WICU patients, prophylaxis should be stopped ontransfer out of the unit.TREATMENT NOTES• Fluconazole prophylaxis has been ineffective in some groups andshould be limited to those listed above.• Use of Fluconazole has led to the emergence of resistant Candida spp.Reference:Fluconazole prophylaxis in surgical patients: Ann Surg 2001;233:542.103salPre-operative and pre-procedure antibioticiobprophylaxiscrmitinaDrugUsual doseRedosing during procedurecCefazolin2 gQ4H (Q2H for cardiac surgery)ticaCefotetan2 gQ8HylhClindamycin600 mgQ8HopCiprofloxacin400 mgQ8HprGentamicin5 mg/kgNonefoMetronidazole500 mgQ8HesuVancomycin< 70 kg: 1 gQ12Hor71-99 kg: 1.25 gfs>100 kg:1.5 genieldImportant notesuiG•Timing is crucial. Antibiotics must be in the skin when the7incision is made to be effective. They should be given NO more1.5than 1 hour before the procedure.•Cephalosporins can be administered over 3–5 min IV push just beforethe procedure and will achieve appropriate skin levels in minutes.Vancomycin and Ciprofloxacin must be given over ONE HOUR andmust be COMPLETELY infused before the incision is made. Clindamycinshould be infused over 10–20 min. •Post-procedure doses are generally NOT needed (exceptions are notedin table). Single doses pre-procedure have been as effective as post-procedure doses in all studies.•Patients receiving pre-operative antibiotics generally do NOT needadditional antibiotics for endocarditis prophylaxis.•Prophylaxis for patients already on antibiotics:•For antibiotics other than Vancomycin: Hold standing dose until 1hour beforeincision•For Vancomycin: Redose a full dose if 8 hours have passed sincethe last dose or a half dose if fewer than 8 hours have passed inpatient with normal renal function104ProcedurePre-op prophylaxis recommendationssalUrologic surgeryobiTransrectal prostate biopsyCefotetan crPCN allergy: Ciprofloxacin miTransurethral surgery (e.g. TURP,Cefazolin tinTURBT, ureteroscopy, cystouretoscopy)PCN allergy: GentamicinaLithotripsyCefazolin ctiPCN allergy: GentamicincNephrectomy or radical prostatectomyCefazolinaylPCN allergy: ClindamycinhRadical cystectomy, cystoprostatectomy Cefotetan opor anterior exenterationPCN allergy: Clindamycin PLUSGentamicinprPenile or other prosthesesCefazolin OR [Vancomycin ±Gentamicin]foPCN allergy: [Clindamycin OR Vancomycin] ±eGentamicinsuHead and neck surgeryorfMajor procedure with incision of oral or Cefotetan or Clindamycinsepharyngeal or sinus mucosaPCN allergy: ClindamycinnMajor neck dissection or parotid dissectionCefazolin eliPCN allergy: ClindamycindThyroid/parathyroid surgeryProphylaxis not recommendeduiGTonsillectomyProphylaxis not recommended71.Cardiac surgery/procedure5Median sternotomy/uncomplicated Cefazolinheart transplantPCN allergy: Vancomycin ±GentamicinMedian sternotomy/heart transplant – Cefazolin PLUSVancomycinprevious VAD or MRSA colonization/infectionPCN allergy: Vancomycin ±GentamicinPacemaker placementCefazolinPCN allergy: ClindamycinLung transplantPiperacillin/tazobactam 4.5 g IV Q6HPCN allergy: Vancomycin PLUSCiprofloxacinIf CF patient: please confirm with transplant IDLVAD/BIVAD placement Vancomycin PLUSCiprofloxacin PLUSFluconazolefor 48 hoursVascular surgeryAll proceduresCefazolinPCN allergy: VancomycinProphylaxis not recommended for carotid surgeryunless risk of infection thought to be highThoracic surgeryAll cases except esophagealCefazolinPCN allergy: ClindamycinEsophageal casesCefotetan PCN allergy: ClindamycinNeurosurgeryCraniotomy (including shunt placement)CefazolinPCN allergy: ClindamycinSpinal fusionCefazolinPCN allergy: Clindamycin OR VancomycinLaminectomyCefazolinPCN allergy: Clindamycin105salProcedurePre-op prophylaxis recommendationsobiGynecologic surgerycrCesarean sectionCefazolin miPCN allergy: Clindamycin tinHysterectomy (abdominal or vaginal) Uncomplicated: Cefazolina Complicated: Cefotetan ctiPCN allergy: Clindamycin PLUSGentamicincaRepair of cystocele or rectoceleCefazolinylPCN allergy: ClindamycinhopOrthopedic surgeryrJoint replacementCefazolin pfoPCN allergy: Vancomycin eOpen reduction of fractureCefazolinsuPCN allergy: Vancomycin orLower limb amputationCefotetan f PCN allergy: Clindamycin PLUSGentamicinseSpinal fusionCefazolinnPCN allergy: Clindamycin OR VancomycinelidLaminectomyCefazolinuiPCN allergy: ClindamycinGArthroscopic surgeryNo data to support prophylaxis 71.General surgery5Inguinal hernia repairUncomplicated: Prophylaxis not recommendedComplicated, recurrent, or emergent: CefotetanPCN allergy: Clindamycin ±GentamicinPEGCefazolin OR Cefotetan PCN allergy: Clindamycin ±GentamicinGastrectomy/hepatectomy/Cefotetan cholecystectomyPCN allergy: Clindamycin ±GentamicinSmall bowel or colon surgery Cefotetan PCN allergy: Clindamycin PLUSGentamicin Whipple procedure or pancreatectomyCefotetan PCN allergy: Clindamycin PLUSCiprofloxacin Appendectomy (uncomplicated), if Cefotetan complicated or perforated, treat asPCN allergy: Clindamycin PLUSGentamicinsecondary peritonitisPenetrating abdominal traumaCefotetan PCN allergy: Clindamycin PLUSGentamicinMastectomyProphylaxis not recommendedMastectomy with lymph node dissectionCefazolinPCN allergy: ClindamycinPlastic surgeryTissue expander insertion/all flapsCefazolinPCN allergy: ClindamycinRhinoplastyNo prophylaxis OR Cefazolin PCN allergy: No prophylaxis OR Clindamycin106ProcedurePre-op prophylaxis recommendationssaliTransplant surgeryobPancreas or pancreas/kidney transplantCefotetan crPCN allergy: Clindamycin PLUSCiprofloxacinmiRenal transplant/adult live donorCefazolin tiPCN allergy: Clindamycinna Liver transplantCefotetancPCN allergy: Clindamycin PLUSCiprofloxacinticaInterventional radiology proceduresylhBiliary/GI proceduresCefotetan opPCN allergy: Gentamicin PLUSMetronidazoleLiver chemoembolization or percutaneousCefotetan prfablation with history of biliary surgery orPCN allergy: Clindamycin PLUSGentamicino instrumentationesLiver, renal, lung†chemoembolization or Prophylaxis not recommendedu percutaneous ablationorfFibroid/uterine artery embolizationProphylaxis not recommended sVascular malformation embolizationProphylaxis not recommended unless necrotic skinenthen Cefazolin or PCN allergy: ClindamycinielLymphangiogram embolizationCefazolin (not ablation) PCN allergy: ClindamycinuidGUrologic proceduresCefazolin 7PCN allergy: Gentamicin 1.Placement of implantable access port Cefazolin5(e.g., Mediport®)PCN allergy: ClindamycinPlacement of tunneled cathetersProphylaxis not recommended†Pretreatment w/antibiotics can be considered for patients w/COPD or h/o recurrentpost-obstructive pneumonia107salProphylaxis against bacterial endocarditisiobcrNOTES:mi•These recommendations are new as of May 2007 and represent atinsignificant departure from previously published guidelines.ac•Patients who have received antibiotics for surgical prophylaxis do notticneed additional prophylaxis for endocarditis.aylhAntibiotic prophylaxis solely to prevent endocarditis is notoprecommended for GU or GI tract procedures.prfoCardiac conditions associated with a high risk of endocarditis foreswhich prophylaxis is recommended prior to some dental andurespiratory tract procedures and procedures involving infectedorfskin or musculoskeletal tissuese•Prosthetic cardiac valveneli•Previous episode of infective endocarditisuid•Congenital heart disease (CHD)G•Unrepaired cyanotic CHD, including palliative shunts and conduits71•Completely repaired congenital heart defect with prosthetic.5material or device, whether placed by surgery or by catheterintervention, during the first 6 months after the procedure•Repaired CHD with residual defects at the site or adjacent to thesite of a prosthetic patch or prosthetic device •Cardiac transplantation recipients who develop cardiac valvulopathyAntibiotic prophylaxis is recommended for the following dentalprocedures ONLY:•Manipulation of gingival tissues or periapical region of teeth•Perforation of oral mucosaAntibiotic prophylaxis is recommended for the followingrespiratory tract procedures ONLY:•Incision or biopsy of the respiratory mucosaAntibiotic regimens•Amoxicillin 2 g PO 1 hour beforeprocedureOR•PCN allergy: Clindamycin 600 mg PO 1 hour before procedureOR•PCN allergy: Azithromycin 500 mg PO 1 hour before procedureOR•Patient unable to take oral medication: Ampicillin 2 g IM/IV 1 hourbefore procedure OR Cefazolin 1 g IM/IV 5 minute push prior toprocedureReference:AHA Guidelines for Prevention of Infective Endocarditis: Circulation 2007; 115(15):e408. 108Prophylactic antimicrobials for patients with salsolid organ transplantsobicrNOTE:PCP, anti-viral, anti-fungal prophylaxis is generally restarted in patients startingmitherapy for acute rejection. All doses assume normal renal function; dose modificationstinmay be indicated for reduced CrClacKidney, kidney-pancreas, pancreas, liver transplantsticIndicationAgent and doseDurationaylhAnti-viral prophylaxis (CMV, HSV, VZV)CMV D-/R-Acyclovir 400 mg PO BID3 monthsopprCMV D+/R+Valgancyclovir 450 mg PO daily3 monthsfoCMV D-/R+Valgancyclovir 450 mg PO daily3 monthseCMV D+/R-Valgancyclovir 900 mg PO daily6 monthssuAnti-fungal prophylaxisorfKidneyClotrimazole troches 10 mg PO Q6H or sNystatin suspension 500,000 units/15 mL Q6H1monthenPancreas and kidneyFluconazole 400 mg PO daily 1 montheliLiver Fluconazole 400 mg PO daily3 monthsuidPCP prophylaxisFirst line: TMP/SMX one SS tablet PO daily6 monthsGSecond line: Atovaquone 1500 mg PO daily71.Treatment notes:TMP/SMX therapy reduces risk of infection with Listeriaspp.,5Nocardiaspp., and Toxoplasmosis, but does not eliminate risk. For splenectomizedpatients, antibacterial prophylaxis with Penicillin (or Doxycycline if PCN allergy) isrecommended for 1 year.Heart transplantsIndicationAgent and doseDurationAnti-viral prophylaxis (CMV, HSV, VZV)CMV D-/R-No prophylaxis unless HSV IgG or VZV IgG 3 monthspositive. If positive serology, Valacyclovir 500 mg PO BID OR Acyclovir 400 mg PO BIDCMV D+/R+Valganciclovir 900 mg PO daily3monthsCMV D-/R+Valganciclovir 900 mg PO daily3monthsCMV D+/R-Valganciclovir 900 mg PO daily6 monthsAnti-fungal prophylaxisNystatin suspension 500,000 units Q6H1 monthPCP prophylaxisFirst line: TMP/SMX SS one tablet PO daily OR12 monthsTMP/SMX one DS tablet PO three times/weekSecond line: Dapsone 100 mg PO daily (sulfa allergy)Toxoplasmosis prophylaxisToxo D-/R+ OR D+/R+First line: TMP/SMX one SS tablet PO daily OR 12 monthsTMP/SMX one DS tablet PO three times/week. Second line: Dapsone 100 mg PO daily PLUSPyrimethamine and LeucovorinToxo D+/R-TMP/SMX one DS tablet PO three times/weekLifelong D=donor,R=recipient, (–) = seronegative, (+) = seropositive(continues)109salLung transplantsobiIndicationAgent and doseDurationcrAnti-viral prophylaxismiCMV D-/R-No prophylaxis unless HSV IgG or VZV IgG 3 monthstinapositive. If positive serology, Valacyclovir c500 mg PO BID OR Acyclovir 400 mg PO BIDticCMV D-/R+ OR D+/R+Ganciclovir 5 mg/kg IV Q24H x 14 days, then3 monthsaylValganciclovir 900 mg PO daily x 78 dayshCMV D+/R-Ganciclovir 5 mg/kg IV Q12H x 14 days, 3 monthsopthen 5 mg/kg IV Q24H x 78 days prfAnti-fungal prophylaxiso eNo Aspergillus Inhaled Amphotericin B per protocolDuring the sucolonizationinitial orhospitalization f Nystatin 5 mL swabbed in mouth Q6H1 month senOR Clotrimazole troches 10 mg PO Q6Hpost D/CeliAspergillus colonizationVoriconazole 200 mg twice daily 3–6 months uidPCP prophylaxisFirst line: TMP/SMX one DS tablet PO At least Gthree times/week12 months 71Second line: Dapsone 100 mg PO daily (sulfa allergy).5Second line: Atovaquone 1500 mg PO daily (sulfa allergy& G6PD deficiency)D = donor, R = recipient, (–) = seronegative, (+) = seropositive110Neutropenic feverstsoh NOTE:These guidelines were developed for use in BMT and leukemiacnipatients and may not be fully applicable in other instances.eopDefinitionstru• Neutropenia: ANC < 500/mm3en • Fever: Temp > 38.0°C times two at least 2 hours apart OR n iTemp > 38.3°C times onesalobiTREATMENTcrAlways tailor antibiotics based on susceptibility profilesmitina If the patient is hypotensive or otherwise unstable, see “Treatment offo clinically unstable patients” (p. 112).esu orInitial feverf s• Piperacillin/tazobactam 3.375 g IV Q4H (preferred if Pseudomonaseniexpected) elORuid• Cefepime 2 g IV Q8HG 8OR1.5• Serious allergy to PCN, defined as anaphylaxis or Stevens-Johnsonsyndrome: Strongly consider allergy consult to verify allergy in patientswith unclear histories (see section on penicillin allergy) • Ciprofloxacin 400 mg IV Q8H PLUS[Aztreonam 2 g IV Q8H OR Tobramycin (see dosing section, p. 132)] PLUSVancomycin (seedosing section, p. 138)NOTES:• Discontinue mucositis prophylaxis (Ampicillin or Vancomycin) whenantibiotics are started to treat fevers, BUT continue Norfloxacin for GIdecontamination.• Consider adding Vancomycin in non-PCN allergic patients if a seriouscatheter-related infection is suspected (e.g., there is warmth andredness at the catheter site).For patients who remain febrile or develop a new fever after 72hours on antibiotics above and are NOT hypotensive (“Secondfever”):• Continue antibiotics above and ADDOR• AmBisome®3 mg/kg IV Q24H (for patients with a history ofneutropenia ≤10 days and without evidence of fungal infection)111stsORoh• AmBisome®5 mg/kg IV Q24H (for patients with a history of cnineutropenia > 10 days or evidence of fungal infection)eopNOTE:Discontinue Fluconazole if AmBisome®or Micafungin are started.truenFor patients who remain febrile or develop a new fever after 72 nhours on both antibacterial agents AND Amphotericin B but are isalNOT hypotensive (“third fever”):obiOption 1:crmi• Add Vancomycin (see dosing section, p. 138) IF and ONLY IF thetinpatient has a documented Gram-positive infection that is susceptiblea only to Vancomycin.fo esOption 2:u • Continue current regimen (some patients will take longer to defervesce)orf sOption 3:en• No PCN allergy: STOP Piperacillin/tazobactam or Cefepime and STARTeliMeropenem 1 g IV Q8H.uidG• PCN allergy: STOP Aztreonam or Tobramycin and START Amikacin (see 81dosing section, p. 132) .5Antibiotic treatment of patients who are CLINICALLYUNSTABLEdue to a possible infectious cause at ANY time duringneutropenia:Transplant ID consult recommended• AmBisome®5 mg/kg IV Q24H PLUS• Vancomycin (see dosing section, p. 138) PLUS• Amikacin 8 mg/kg IV Q8H (see dosing section, p. 132, AND“Treatment notes,” below) PLUS• Meropenem 1 g IV Q8HFor patients with severe PCN allergy, replace Meropenem with:• [Aztreonam 2 g IV Q8H or Ciprofloxacin 400 mg IV Q8H]TREATMENT NOTES• Antibiotics should ALWAYS be narrowed based on positive cultures.• It is recommended that all patients receiving aminoglycosides havelevels obtained around the third dose:• A troughlevel should be drawn just prior to administration ofthe third dose.• A peaklevel should be drawn 30 minutes after the infusion ofthe third dose.• If the patient is critically ill and has an unclear volume status,some advocate obtaining a peak level after the first dose toensure efficacy.112Prophylactic antimicrobials for patients with stsexpected prolonged neutropeniaoh cni1. Bone marrow transplant patientseopIndicationAgent and doseDurationtruGI decontaminationNorfloxacin 400 mg Day zero until enPO BIDANC > 500/mm3 nCandida prophylaxisFluconazole 400 mg Day zero until isPO once dailyANC > 500/mm3alAnti-viral prophylaxisValacyclovir 500 mg Day zero until day 28obi(if HSV or VZV IgG PO TID [If unable to crpositive or pending)take POmitiAcyclovir 250 mg/m2naIV Q12H] foStreptococcal Ampicillin 2 g IV Q6HDay zero until “First Fever” eprophylaxis for [If severe PCN allergyantibiotics are startedsu patients with Vancomycin 1 g IVOR mucositis is < grade 2ormucositis*Q12H]f se* For outpatients: Amoxicillin 500 mg PO TID (if PO tolerated) ORnielVancomycin 1 g IV Q12H (if PCN allergy) ORno prophylaxis (seeuidtreatment notes on the next page)G 812. Leukemia patients.5IndicationAgent and doseDurationGI decontaminationNorfloxacin 400 mg Day 1 untilPO BIDANC > 100/mm3Anti-viral prophylaxisValacyclovir 500 mg Day 1 until(if HSV Ig G positivePO TIDANC > 100/mm3or pending)[If unable to take PO Acyclovir 250 mg/m2IVQ12H]Streptococcal Ampicillin 2 g IV Q6HDay 8 of chemotherapy prophylaxis for[If severe PCN allergyuntil “First Fever” antibioticspatients with Vancomycin 1 g IVare started OR mucositis*Q12H] ANC >100/mm3on the way upPCP prophylaxis Bactrim 1 SS once daily Until immunosuppression(ALL, CLL, lymphoma OR [If Sulfa allergy resolvesand myeloma Dapsone 100 mg pts only)once daily]* For outpatients: Amoxicillin 500 mg PO TID (if PO tolerated) ORVancomycin 1 g IV Q12H (if PCN allergy) ORno prophylaxis (seetreatment notes below)3. Solid tumor patientsThe use of prophylactic antibiotics in neutropenic patients who have solidtumors has not been studied formally and is not routinely recommended.113stsoTREATMENT NOTESh c• There is some controversy surrounding the utility of anti-streptococcalnieprophylaxis in patients with mucositis.optrueGuidelines for the use of antifungal agents in n nhematologic malignancy patients isaliFilamentous fungiobcrmiTREATMENTtinaAspergillusspp. fo Initial therapyesu• Voriconazole 6 mg/kg IV/PO Q12H times two doses then 4 mg/kg orIV/PO Q12H (see Voriconazole guidelines, p. 20, for more information).f sOReni• AmBisome®5mg/kg IV Q24HeluidNOTES:G • Voriconazole is considered by many to be the first-line treatment of81suspected filamentous fungal infections in the immunocompromised.5host as most of these infections are caused by Aspergillusspecies.Although the data are limited, Voriconazole appears more effectivethan Amphotericin for this very serious infection.• Combination antifungal therapy is not recommended for empirictherapy of aspergillosis.Treatment failure• The Tucker ID consult service (#4-0242) should be involved in thesecases to assist in antifungal selection and eligibility for ongoing clinicaltrials.• Treatment failure defined as:• Persistent fever beyond 96 hours• Worsening clinical status at ANY time after starting therapy definedas: hypotension, worsening respiratory status, evidence ofembolization• Worsening radiologic findings• Patients receiving Voriconazole should be appropriately dosedusing actual body weight (mg/kg) and have therapeutic levelsbefore being considered treatment failures. See p. 20 for dosingand therapeutic monitoring.• Micafungin PLUS[Voriconazole OR AmBisome®]NOTE:There is no convincing evidence to suggest that any of theagents would be superior in patients who fail to respond to the first114agent. In vitrodata suggest that Micafungin in combination withstVoriconazole may be the most effective approach in those who fail tosohrespond to Voriconazole alone. cnieFusariumspp.op• ID consult should be involved in these cases.true• Voriconazole 6 mg/kg IV/PO Q12H times two doses then 4 mg/kgn nIV/PO Q12H (see Voriconazole guidelines, p. 20, for more information). isDose escalation may be necessary for some patients.aliobPseudallescheria boydii (Scedosporium spp.)cr• Voriconazole 6 mg/kg IV/PO Q12H times two doses then 4 mg/kgmitinIV/PO Q12H (see Voriconazole guidelines, p. 20, for more information).a foNOTE: es• Treatment with other agents has yielded disappointing results.u Voriconazole appears to be the best option but the data are limited.orf senZygomycoses (Mucor, Rhizopus, Cunninghamella,etc.).eli• AmBisome®5 mg/kg IV once dailyuid• Posaconazole 200 mg PO Q6H for 7 days then 400 mg PO G Q8H – Q12H can be considered in combination with AmBisome®in the81.acutely ill patient or for outpatient monotherapy once the patient is5stable. ID consult required.• Surgical debridement and correction of underlying risk factors (e.g.acidosis, hyperglycemia) are critical.• Voriconazole and Micafungin should not be used as a single agent.CandidaTREATMENT• YEAST IN A BLOOD CULTURE SHOULD NEVER BE CONSIDERED ACONTAMINANT. • See sections below on empiric therapy and on pathogen-specifictherapy.Unspeciated candidemia• Micafungin 100 mg IV Q24HOR• AmBisome®3–5 mg/kg IV Q24HIf the yeast is C. albicansor C. glabrata,the recommendations for C.albicansnoted below can be followed. If the yeast is not C. albicans,await speciation before modifying therapy as recommended below.115stsNOTE: Micafungin does not cover Cryptococcusoh cniCandida albicanseop• Micafungin 100 mg IV Q24HtruORen• AmBisome®3–5 mg/kg IV Q24H n isNOTE:Patients who are clinically stable and no longer neutropenic canalibe switched to Fluconazole if the organism is susceptible.obcrmiCandida glabratatina• Micafungin 100 mg IV Q24H foOR es• AmBisome®3–5 mg/kg IV Q24Hu orf Candida kruseiseni• Micafungin 100 mg IV Q24HelORuidG• AmBisome®5 mg/kg IV Q24H 81.NOTE:C. kruseiis intrinsically resistant to Fluconazole and these5infections can be difficult to treat. In stable patients, Voriconazole can beused if susceptible and oral therapy is desired. (See p. 20 for dosing). Candida parapsilosis• AmBisome®3–5 mg/kg IV Q24H NOTES:• Most C. parapsilosisisolates remain susceptible to Fluconazole, whichcan be used in stable and non-neutropenic patients. • There are limited data that suggest that Micafungin may be inferior toAmphotericin B in these infections.Candida tropicalis• Micafungin 100 mg IV Q24HOR• AmBisome®3–5 mg/kg IV Q24H116sTREATMENT NOTEStsohMicrobiology cCandidemia at The Johns Hopkins Hospital Oncology Center—nie8/2007–4/2009optrueOrganism#Fluconazole susceptibilityn nC. albicans44/4 isC. glabrata32/3aliC. parapsilosis22/2obC. tropicaliscr99/9mitiS – susceptible (MIC ≤8); I – intermediate (MIC = 16–32); R – resistant (MIC ≥64)na fNotes on antifungal susceptibility testingo e• Susceptibility testing for Fluconazole, Itraconazole, Voriconazole,su Flucytosine (5-FC), and Micafungin is performed routinely on the firstorfyeast isolate recovered from blood. se• Fluconazole and Micafungin susceptibilities are reported on all bloodniisolates.el• If the isolate is resistant (R) or dose-dependent susceptible (DD-S) touidGFluconazole, then Micafungin susceptibility will be reported. 8• Susceptibility testing for conventional Amphotericin B is done routinely1.5for C. lusitaniaeand C. guillemondiiand for other organisms byrequest.• Susceptibility testing should be considered when: • Mucocutaneous candidiasis is refractory to Fluconazole• Treating osteomyelitis, meningitis, or endophthalmitis withFluconazole• Blood cultures are persistently positive on Fluconazole• Non-routine susceptibility testing can be arranged by calling themycology lab at 5-6148Reference:IDSA Guidelines for Treatment of Candidiasis: Clin Infect Dis 2009;48:503.117yApproach to the patient with a history ergallof penicillin allergy nillPenicillin reactions – Incidencecini• 80-90% of patients who report they are “allergic” to PCN actually haveenegative skin tests and are not at increased risk of an allergic reaction. pfo • Penicillin reactions of some type occur in 0.7 to 10% of all patientsyorwho get the drug.ts• BUT: The incidence of anaphylactic reactions is 0.004% to 0.015%.hi a• Rates of cross-reaction allergies to cephalosporins are unknown but htthought to be low.wi • Rates of PCN and carbapenem skin test cross reactivity are 47%,tnealthough clinical rates of hypersensitivity reactions in patients withtiareported PCN allergy who receive carbapenems are 9–11%. pe• Cross reactions to monobactams (Aztreonam) do NOT appear to occur.ht oPenicillin skin testingt hc• When done correctly, is highly predictive of serious, anaphylacticaoreactions.r• Patients with a negative skin test are NOTat risk for anaphylacticApp reactions.1.6• Rarely, skin test negative patients may get mild hives and itchingfollowing penicillin administration but these RESOLVE with continuedtreatment.• Skin tests cannot predict dermatologic or GI reactions or drug fevers.Penicillin reactions—Types• Immediate(type 1) – Anaphylaxis, hypotension, laryngeal edema,wheezing, angioedema, urticaria• Almost always occur within 1 hourof administration. Hypotensionalwaysoccurs soon after administration• Can be predicted by skin tests• Accelerated– Laryngeal edema, wheezing, angioedema, urticaria(NOT hypotension)• Occur within 1-72 hours of administration• Can be predicted by skin tests• Late– Rash (maculopapular or morbilliform or contact dermatitis),destruction of RBC, WBC, platelets, serum sickness• Almost always occur after 72 hours of administration• Rashes sometimes go away despite continued treatment• Maculopapular and morbilliform rashes DO NOT progress toStevens-Johnson syndrome• Late reactions are NOT predicted by skin tests• Stevens-JohnsonSyndrome– exfoliative dermatitis with mucousmembrane involvement118• Almost always occur after 72 hours of administrationyg• NOT predicted by a history of rash OR by skin testserlalApproach to the patient with reported penicillin allergy nlli• Brief, focused history can be VERY helpful.cini• Questions to ask:e p1. How long after beginning penicillin did the reaction occur?fo 2. Was there any wheezing, throat or mouth swelling, urticaria?yor3. If a rash occurred, what was the nature of the rash? Where was ittsand what did it look like?hi a4. Was the patient on other medications at the time of the reaction? ht5. Since then, has the patient ever received another penicillin orwi tcephalosporin (ask about trade names like: Augmentin, Keflex,neTrimox, Ceftin, Vantin)?tia6. If the patient received a beta-lactam, what happened? pehtInterpreting the history of the patient reporting penicillin allergy ot h• ANY patient who has a history consistent with an immediatecareaction (laryngeal edema, wheezing, angioedema, urticaria)orSHOULD NOT receive beta-lactams without undergoing skinApp testing first EVEN IF they have received beta-lactams with no1.problems after the serious reaction.6• Patients who report non-anaphylactic reactions and have receivedother penicillins without problems DO NOT have penicillin allergyand are not at increased risk for an allergic reaction compared tothe general population.• Patients who report non-anaphylactic reactions and have receivedcephalosporins can get cephalosporins but not necessarily PCNs.• Patients who report a history of a non-urticarial rash that is NOTconsistent with Stevens-Johnson syndrome (target lesions withmucous membrane inflammation) after more then 72 hours of gettingpenicillin are not at increased risk for an adverse reaction. Theyshould, however, be watched closely for development of rashes.• Patients who report reactions consistent with serum sickness (rare)can receive either penicillins or cephalosporins with carefulmonitoring for recurrence.• Patients who report GI symptoms (diarrhea, nausea) probably donot have penicillin allergy and do not appear to be at increased riskfor an adverse reaction. They should be closely observed forrecurrent symptoms and be given supportive therapy if they occur.References: JAMA 2001;285:2498.Use of carbapenems in patients with PCN allergy: J Antimicrob. Chemother 2004;54:1155–7. Ann Intern Med 2007;146:266–9.119”eCombination therapy or “double-coverage” ofagerGram-negative bacterial infectionsvoc Reasons to consider combination therapyeublSynergyo• Occurs when inhibitory or bactericidal activity of combination therapy is“D 2greater than would be expected from the sum of the activities of the.6individual agents• Synergy for Gram-negative infections is of major value only when thebacterium is resistant to one or both of the drugs in the combination.• Synergy has been best established for beta-lactam and aminoglycosidecombinations.• Synergy between other drug combinations is less predictable and hasunclear clinical significance. Prevention of emergence of resistance • Emergence of resistance on therapy is uncommon, occurring in5–10% of infections treated.• Emergence of resistance to beta-lactams while on therapy with theseagents occurs in ~20% of patients infected with organisms withinducible beta-lactamases (Serratia, Enterobacter, Citrobacter,Acinetobacter); beta-lactams are best avoided in these patients if otheroptions are available.• Emergence of resistance is more common in pneumonia andosteomyelitis due to decreased antibiotic penetration at these sites;attention should be given to appropriate dosing in these patients.• The addition of additional agents may lead to increased toxicity fromadverse drug reactions.Broadening empiric coverage in the event that the causativeorganism is resistant to one agent• Should be considered in patients with life-threatening infections(ventilator-associated pneumonia, sepsis).• Second agent should offer additional coverage and generally will be anaminoglycoside at JHH.• Coverage MUST be narrowed based on culture results; negativecultures can be used to rule out infections with most organisms.Data Regarding Combination Therapy• An early study by Hilf suggested that combination therapy was superiorto monotherapy in patients with Pseudomonasbacteremia BUT 84% ofmonotherapy patients received inadequate monotherapy with anaminoglycoside. Five more recent studies have not shown a differencein mortality when patients received appropriate monotherapy for120Pseudomonasbacteremia.”e• Recent prospective studies have not shown a benefit to combinationagtherapy over monotherapy in the treatment of serious Gram-negativeervinfections in both non-neutropenic AND neutropenic patients. oc • Two recent meta-analysis showed no difference in outcomes ofepatients with sepsis or febrile neutropenia treated with beta-lactamsubloalone vs beta-lactam/aminoglycoside combinations although patients in“D the latter group had a higher incidence of nephrotoxicity.2.6Recommendations for use of combination therapy• Data suggest that monotherapy is sufficient for the treatment of mostGram-negative infections. • The use of 2 agents to treat proven or suspected Gram-negativeinfections should be limited to the following situations:1. Empiric treatmentof serious infections manifested byhypotension, pressor dependence or mechanical ventilation(primarily to broaden spectrum). 2. Documented infectionwith a resistant Gram-negative organism(particularly Pseudomonas, Acinetobacter, Citrobacter,Enterobacter, and Serratia) when antibiotic penetration to the siteof infection is poor (pneumonia, osteomyelitis). Consideration canbe given to stopping one of the agents after 5–7 days of therapywhen the bacterial burden has decreased.3. Documented infectionwith a highly resistant organism aftersynergy testing shows an advantage to a beta-lactam/aminoglycoside combination. Call ID to discuss synergytesting (3-8026).• The second agent should be an aminoglycoside in most cases.Fluoroquinolone resistance is common among Gram-negativeorganisms at JHH.• Double beta-lactam combinations should not be used. References:Am J Med 1989;87:540.Antimicrob Agents Chemother 1994;38(6):1309.Antimicrob Agents Chemother 1997;41:1127.BMJ 2003;326:1111.BMJ 2004;328:668.Clin Infect Dis 1995;20(5):1217.Int J Antimicrob Agents 1999;11:7.Pharmacother 1995;15(3):279.121oltrHospital Epidemiology and Infection Control noC(HEIC) no• HEIC is located is located in Osler 425, phone 5-8384tice• Office hours are Monday-Friday, 8:00 a.m. to 5:30 p.m.fn• After hours, an Infection Control Practitioner (ICP) can be reached by I& pager at 3-3855yog• Consult the HEIC Web site (www.hopkinsmedicine.org/heic) for detailedolisolation charts, HEIC policies, and surveillance informationmieidHand hygiene Ep• Hand hygiene measures are the single most important strategy foraltpreventing healthcare-associated infections.spio• If hands are not visibly soiled, then alcohol-based hand sanitizers are Hrecommended for cleaning. If hands are visibly soiled, wash hands with1.7soap and water for 10–15 seconds.• Hand hygiene is required upon entering a patient room, upon exiting,and between patients in a semi-private room.• Use soap and water upon exiting the room of a patient with C. difficileinfection.• No artificial fingernails are permitted for any staff member who haspatient contact.Bloodborne pathogen exposures (needlestick or other exposure)The prompt treatment of injuries and exposures is vital to prevent thetransmission of disease. Whatever the exposure, IMMEDIATE cleaning ofthe exposure site is the first priority.• Skin wounds should be cleaned with soap and water• Mucous membranes should be flushed thoroughly with water• Eyes should be irrigated with a liter of normal salineAfter cleaning the exposure site, call 5-STIX (5-7849) and followinstructions to contact the ID physician. Workplace injuries should bereported immediately on the “Employee Report of Incident Form” and tothe Occupational Injury Clinic(Blalock 139, Monday–Friday, 7:30 a.m.to 4 p.m., 5-6433).122Communicable diseases—exposures and reportingoltrHEIC should be notified:no• If patients or HCWs are exposed to a communicable disease (i.e.C nmeningococcal disease, varicella, TB etc.)oti• About HCWs with acute hepatitis A, B or C, Salmonella, orcefpneumonia requiring hospital admissionn I• About any unusual occurrence of disease or cluster, particularly& ydiseases that have the potential to expose many susceptibleogindividualsol• Suspicion or diagnoses of the following diseases (diseases with mierequire immediate notification by phone or pager). If disease is in a☎pidHCW, notify HEIC and Occupational Health (98 N. Broadway, Suite E421, Monday–Friday, 7:30 a.m. to 4:00 p.m., 5-6211) immediatelyaltispoAnthrax Rabies HAvianInfluenza ☎Ricin toxin ☎1.7Botulism ☎Rubella (German measles)☎Brucellosis ☎SalmonellosisCreutzfeldt-Jakob disease (CJD) SARS Diphtheria Scabies ☎Glanders ☎☎ShigellosisHighly resistant organisms (i.e. VISA,☎Smallpox (orthopox viruses) VRSA) Streptococcal Group A or B invasive☎Legionellosis☎disease Measles (rubeola) Tuberculosis ☎Meningococcal disease ☎Tularemia Monkeypox ☎Varicella (chickenpox or disseminated☎☎Mumps ☎zoster) Pertussis Viral hemorrhagic fever ☎Plague ☎Yellow Fever Poliomyelitis☎☎☎Q Fever Physicians are required to report communicable disease to the BaltimoreCity Health Department (410-396-4436, fax: 410-625-0688). For acomplete list of communicable diseases, see the HEIC Web site, theDHMH Web site, www.dhmh.state.md.us/ or the BCHD Web site,www.baltimorecity.gov/government/health/index.html.123snoInfection control precautionstiuaStandard PrecautionscerAll employees must follow Standard Precautions for all patients as pfollows:oltrno• Routine hand hygiene• Bag contaminated linen at point of usec n• Consistent and correct glove use • Regular cleaning of environmentalosurfaces tic• Appropriate use of gowns to prevent • Routine cleaning or disposal ofefncontamination of uniform/clothingpatient-care equipment I• Appropriate use of masks, eye • Strict adherence to2.7protection and face shields (i.e., when occupational safety requirementssuctioning, or when splash likely)IC admission codesUsed to inform HCWs of the need for isolation on readmission to JHHbased on the following code system:CodePrecautionsReason for PrecautionsIC01ContactVancomycin Resistant Enterococcus (VRE)IC02ContactMethicillin Resistant Staphylococcus aureus(MRSA)IC03MaximumVancomycin Resistant Staphylococcus aureus(VRSA) OR Vancomycin IntermediateStaphylococcus aureus(VISA)IC04Contact + AirborneChickenpox or disseminated zosterIC05Airborne, Neg. PressureMDR TuberculosisIC06Infection Control use only IC07Contact, Private RoomBoth VRE and MRSAIC08Contact, Specified locationBurkholderia cepaciaIC09Contact, Private roomMDR AcinetobacterIC10Contact, Private roomMDR Gram negative rod124.sesdrie nogertehoboem tiatot ohsat tuccd Caanieon annss gsEIccrHeleom u tie ns mooA,of praublnorcauitd unesstur RSon oltreps mureinlpuexca)stVtr/enAretinr coothieedquio, uin scfon MarPre(RYesNis ToYesVISdi nts s oentimonciatonsefredtinquienau Imcreod tex2.m†oreal pProecns5at7‡nene eokrnenreiN9mmintd er ocogf ib Iruooro)ress§rcaeiR r diechres e. Air drbeulquPe od uitirooAPer clbs(bRYesPAentNNTB,ostzeannewe iostct blC zataEIr toong HCne on fh withial otoatbollon srieolfd sre ie esetmctnsleoan iquo iThoun fb oi)un*rsre tted d 3 ise fx beuentr a, tiezgilgeons. canretirhinentoptianopoatiennreraquwitpentu atiaucDrofleniPoeohopenkcm (RcNIf ofTo NInmif cire5 Pchd anisN9d rg§onsr artidoroan eauR anchcPost, StaeC.ostzreo EIess pPAd hr toHnse a e onlomff,dir son d frnctirooamitiattcud uder C.beodire)rete rwrdonttakrA,aio paqui cncaoenoentr mreiquir eohoo oRSoe toinoCrPvcd (pRcNNToNMk faoeon e ntas husatiote olbsia mmue nbsrim iweo d ist ofC N95e e anEIphthin esmupyi Hdian rmunr oese te d e megrihieoano tho usa-ostztgd ttnteis ellr r, Caaneoigtssd ce atce cnreritituinsblrefeesrVaoon ae trsequoszopirere ttid ue tasrovulr aauete)mPGN oeo plroed eatcacooend fg iseplrelnwhnrpmd, or osyndOesrePecel ls mie oeHcw ao tcEntquiestiese ona /rketCWsslgoivw empoliroonRFit-HDiJHThThf(sPDMasGOxaE* †‡ § 125snoDisease-specific infection control tiarecommendationsndemmCreutzfeldt-Jakob disease (CJD)oCJD, variant CJD and other diseases caused by prions are resistant to acenumber of standard sterilization and disinfection procedures. Iatrogenic roltransmission of CJD has been associated with percutaneous exposure totrnmedical instruments contaminated with prion/central nervous systemoc (CNS) tissue residues, transplantation of CNS and corneal tissues andnorecipients of human growth hormone and gonadotropin. Transmission ofticeCJD has not been associated with environmental contamination or fromfnperson-to-person via skin contact. The following additional precautions icfimust be made when processing equipment that could be contaminatedciewith prion related material:sp• Notify HEIC immediately of any suspected or confirmed CJD case ande-srefer to the CJD policy on the HEIC Web site.ae• Use disposable equipment whenever possible.s• Label all laboratory and pathology requisitions as suspected CJD and Di3.notify the lab before sending specimens.7• The following are considered highly infective and should be handledwith extreme caution: brain, spinal cord, and optic tissues• The following should be handled as high infectivity even though they areconsidered to be of lower infectivity: CSF, kidney, liver, lung, lymphnodes, spleen, placenta, tonsillar tissue, olfactory tissue, and blood.Methicillin-resistant Staphylococcus aureus(MRSA)Routine active surveillance cultures for MRSA are performed to trackpatients with MRSA. Surveillance culture results are found in theelectronic patient record with the test name “MRSA Surv. Cult.” When aculture is positive for MRSA the patient is placed on ContactPrecautions.The results are to be used for isolation purposes, not toguide therapy or clinical care. The overwhelming majority of positivesurveillance cultures represents colonization, not infection, andshould not prompt any antimicrobial therapy.Surveillance cultures should be obtained upon admission and weekly inthe following units: MICU, OSL-8, WICU, CSICU, SICU/IMC, Nel-7, WGA-5,WGB-5, WGC-5, WGD-5, NCCU, CCU/CCP, PICU.A swab of the anterior nares should be obtained and sent for culture.To remove a patient from MRSA precautions, cultures from the originalsite of infection and 2 nares cultures taken ≥72 hours apart must benegative. Nares cultures should not be sent if the patient has received126antibiotics active against MRSA in the previous 48 hours. Once this issnaccomplished, call HEIC to review culture data and initiate deflagging.otiaPertussisndeAll patients with pertussis should be placed on Droplet Precautionsformmfive days from the start of therapy. If the patient is not on therapy,ocDroplet Precautions should be continued for three weeks from the onsete rof cough. Private room is required.oltrTreatment:no• Azithromycin 500 mg PO once on day 1, then 250 mg PO daily onc ndays 2–5otiORcef• Macrolide allergy: TMP/SMX 1 DS tablet PO BID for 14 daysn icfiProphylaxis with the above regimens is required for all householdciecontacts within three weeks of exposure. Use the same antibiotic as forsptreatment. All household contacts and HCWs with exposure to the patiente-sashould also have up-to-date immunizations for Bordetella pertussis,esalthough vaccination does not provide post-exposure prophylaxis. Di3.7ScabiesAll patients with conventional or Norwegian scabies should be placed onContact Precautions.Norwegian scabies is a severe form of heavymite infestation.• Private room required unless cohorted.• Patients with conventional scabies must be treated with a scabicideonce, and the precautions may be discontinued 24 hours after thetreatment is completed.• Patients with Norwegian scabies require 2 treatments with a scabicide1 week apart. The precautions may be discontinued 24 hours after thesecond treatment is completed.• Infested clothing and linen should be sealed in a plastic bag for 48hours. The mite will not survive off a human host for more than 48hours. Clothing/patient belongings should be sent home with thepatient’s family/caretaker. Linens and clothing should be washed in thewashing machine on the hot cycle.• If prolonged skin-to-skin contact occurs with a scabies patient,prophylactic treatment is required. Healthcare workers should contactHEIC if an exposure is suspected.Vancomycin-resistant enterocci (VRE)Routine active surveillance cultures for VRE are performed to trackpatients with VRE. Surveillance culture results are found in the electronicpatient record with the test name “Bacteriology-Stool-VRE Stool Surv.127snCult.” When a culture grows VRE, the patient is flagged for ContactotiaPrecautions.The results are to be used for isolation purposes, not tondguide therapy or clinical care. The overwhelming majority of positiveemsurveillance cultures represents colonization, not infection, andmshould not prompt any antimicrobial therapy.oceSurveillance cultures should be obtained upon admission and weekly in rolthe following units: MICU, OSL-8, WICU, CSICU, SICU/IMC, Nel-7, WGA-5,trnWGB-5, WGC-5, WGD-5, NCCU, PICU.oc nA peri-rectal swab should be obtained and sent for culture.oticeThe patient must be off antibiotics for ≥ 48 hours and cultures fromfnoriginal site of infection AND 3 stool or perirectal cultures taken ≥1 icfiweek apart must be negative. Once this is accomplished, call HEIC tociereview culture data and initiate deflagging.spe-sVaricella-ZosteraeImmunocompetent patients with disseminated zoster and allsiimmunosuppressed patients with zoster need Contact AND Airborne D3.Precautions. The following definitions apply to patients with zoster:7• Immunosuppressed:bone marrow transplant within the past year;acute leukemia; lymphomas under treatment; solid organ transplantrecipients; patients receiving cytotoxic or immunosuppressivetreatments, including long-standing steroid treatment; HIV+ patientswith CD4 ≤200• Disseminated:lesions outside of 2 contiguous dermatomesCentral vascular access device (VAD) recommendationsAll healthcare workers who place central lines are required to take theonline VAD training (see HEIC Web site). To prevent central VAD-relatedinfections follow the central line bundle:Insertion• Clean hands thoroughly• ChloraPrep®for patient skin antisepsis• Subclavian is the preferred site for central line insertion• Use full barrier precautions and aseptic technique • Lines placed emergently should be changed as soon as the patient ismedically stableCare• Change a semipermeable transparent central line dressing every 7days, unless it is damp, loose or soiled, in which case change thedressing immediately• Change peripheral IV site and tubing every 96 hours• Remove line as soon as possiblePlease refer to the VAD policy on the HEIC Web site for more details.128sEvidenced-based recommendations for prevention of surgicalnosite infections (SSI)tiaPre-operative interventionsnde• Identify and treat remote site infectionsm• Postpone elective procedures until remote infection is resolvedmoc• Control glucose pre- and post-operativelye r• Encourage the patient to stop smoking at least 30 days pre-operativelyol• Instruct patient to wash with 4% chlorhexidine gluconate (CHG ortrnoHibiclens®) the night before and the morning of surgery. (Directionsc can be found at www.hopkinsmedicine.org/heic)noti• Use appropriate peri-operative antibiotic prophylaxis (see p. 88) that iscefgiven prior to, but no more than 1 hour before, skin incisionn icIntra-operative interventionsfi• Clean hands with surgical scrub sponge 2–5 minutes and brush nails.cieFor subsequent cases Avagard® can be used spe-• Do not remove hair at incision unless necessary for the operationsa• Never shave, only use clippersesi• Hair removal, if necessary, should take place immediately before Dsurgery3.7• If CHG wash not done by patient, clean incision site with CHGimmediately prior to surgery • Prepare the surgical site and surrounding area with an approvedantiseptic and allow to DRY prior to placing drapes• Maintain normal core temperature (36.5°C) throughout the procedure• Control serum blood glucose levels using insulin as necessary• Use aseptic technique when placing IV devices• Use aseptic technique when manipulating stopcocks and ports• Assemble sterile equipment and solutions immediately before use• Administer 80% O2when possiblePost-operative interventions• Place a sterile dressing (as anatomically possible) 24–48 hours postsurgery• Change dressing using sterile supplies and good hand hygiene• Control serum blood glucose levels using insulin as necessaryReferences:Guidelines for prevention of SSI: Infect Control Hosp Epidemiol 1999;20:247.Perioperative oxygen: N Engl J Med 2000;242:161.129msBioterrorismorirBelow are recommendations for treatment, prophylaxis, and infectionertocontrol for the Category A agents of bioterrorism. Information aboutBiother potential agents of bioterrorism can be found on the CDC website 1.at http://www.bt.cdc.gov/index.asp.8Contact HEIC immediately if any of the following agents/diseases aresuspected. The microbiology lab should be notified prior to sendingspecimens (5-6510).Specimens should not be sent via thepneumatic tube.Important phone numbers:• HEIC Infection Control: 5-8384 (3-3855)• Microbiology Lab: 5-6510• Maryland Department of Health and Mental Hygiene, seewww.dhmh.state.md.us/labs/html/terrorism.html for on call numbers • Baltimore City Health Department: 410-396-4436, after hours 410-396-3100• U.S. Army Medical Research Institute of Infectious Diseases USAMRID:301-619-4996, hotline 301-619-4027• CDC Emergency Response Office: 770-488-7100Agent & infection controlTreatment & prophylaxisAnthraxTreatment• Ciprofloxacin 400 mg IV Q12H Infection ControlORStandard precautions; there is no • Doxycycline 100 mg IV Q12H evidence for person to personIf inhalational anthrax, ADD Clindamycin transmission of anthrax.600 mg IV Q8HPatients with meningitis• Vancomycin 22.5 mg/kg IV Q12H PLUSCiprofloxacin 400 mg IVQ8H PLUSRifampin 600 mg IV Q24HProphylaxis• Ciprofloxacin 500 mg PO BID x 60 daysOR• Doxycycline 100 mg PO BID x 60 days Anthrax vaccine may also be recommended by HEIC.BotulismTreatmentThis is a toxin-mediated disease; • Equine antitoxin (acquire from CDC)there is not a role for antibiotics.ProphylaxisInfection ControlNoneStandard precautions130Agent & infection controlTreatment & prophylaxismsPneumonic plagueTreatmentori• Streptomycin 15 mg/kg (max. 1 g) IM/IV Q12HerrtoInfection ControlORBiDroplet precautions for the first • Doxycycline 100 mg IV Q12H 1.48 hours of therapy. A private room Patients with meningitis8is required. Movement of patients• Chloramphenicol 25 mg/kg IV Q6Hshould be limited to essential medicalpurposes only, and a mask should be Prophylaxisplaced on the patient during transport.• Doxycycline 100 mg PO BIDOR• Ciprofloxacin 500 mg PO BIDSmallpoxTreatmentSupportive therapyInfection ControlMaximum + AirborneProphylaxisprecautions.A private room is • Smallpox vaccine should be given required. Movement of patients (preferably within 4 days of exposure)should be limited to essential medical •Preexposure and postexposurepurposes only, and a mask should be vaccination recommended if > 3 years placed on the patient during transport.since last vaccination.TularemiaTreatment• Streptomycin 15 mg/kg (max. 1 g) IM/IV Q12HInfection ControlORStandard precautions; there is no• Gentamicin 5 mg/kg IV Q24Hevidence for person-to-person transmission of tularemia.Prophylaxis• Doxycycline 100 mg PO BIDViral hemorrhagic feversTreatment• Lassa fever, Rift Valley fever, or eitherArgentine, Bolivian, Brazilian, orVenezuelan hemorrhagic feverInfection Control• Ribavirin 30 mg/kg (max. 2 g) IV initial Maximum + Airbornedose, then 16 mg/kg (max. 1 g) IV precautions.A private room is Q6H x 4 days, then 8 mg/kg (max. required. Movement of patients 500 mg) IV Q8H x 6 daysshould be limited to essential medical • Ebola, Marburg, Yellow fever, Omsk purposes only, and a mask should be hemorrhagic fever, Kyasanur Forest placed on the patient during transport.Disease: supportive therapyProphylaxisNoneReferences:Anthrax: JAMA 2002;287:2236Botulinum: JAMA 2001;285:1059Plague: JAMA 2000;283:2281Smallpox: JAMA 1999;281:2127Tularemia: JAMA 2001;285:2763VHF: JAMA 2002;287:2391131ngAminoglycoside dosing and monitoringoritni• Aminoglycosides enhance the efficacy of some antibiotics. Except foromurinary tract infections, aminoglycosides should seldom be used alone to treat infections. nda • The following dosing guidelines do NOTapply to cystic fibrosis or ngOB patients. sio• Aminoglycosides are known to aggravate the symptoms of myasthenia degravis and should NOTbe used in these patients.sidoEstimation of creatinine clearance (CrCl) by Cockcroft-Gaultcyequation:oglnCrCl =(140 – age) (weight in kg*)mi72 (serum creatinine**)x 0.85 (if female)A * Use Actual Body Weight (ABW) unless patient is obese (≥20% over Ideal Body Weight.A(IBW)). For obese patients, use Dosing Body Weight(DBW) = [IBW + 0.4 (ABW – IBW)] IBW female (kg) = (2.3 x inches over 5') + 45.5IBW male (kg) = (2.3 x inches over 5') + 50** For patients with low muscle mass (i.e., many patients > 65 yrs.), some advocateusing a minimum value of 1 to avoid overestimation of CrClExtended interval (“once-daily”) aminoglycoside dosing and therapeutic drug monitoringExtended-interval dosing has become the preferred method of givingaminoglycosides in many cases (see rationale below). However, patientsMUST meet ALL of the following criteria to be eligible forextended-interval dosing:• Creatinine clearance greater than 60 mL/min• Stable renal function (creatinine NOT changed by 0.5 mg/dL or 30% inprevious 48 hours)• Patient is NOT pregnant• Patient does NOT have extensive burns ( > 20% BSA) or trauma• Patient does NOT have ascites, extensive edema, shock, or any othercondition where the volume status is unclear• The aminoglycoside is NOT being used to treat meningitis If the patient does not meet ALL of the criteria above, traditionalaminoglycoside dosing is recommended (see Traditional AminoglycosideDosing)DOSING• GENTAMICIN/TOBRAMYCIN:In most patients, a dose of 5 mg/kgIV once dailyis recommended. Higher doses (7 mg/kg IV once daily)may be required in certain circumstances. Doses should be rounded tothe nearest 10 mg.132• AMIKACIN:In most patients, a dose of 15–20 mg/kg IV once dailyngis recommended. Dose should be rounded to the nearest 50 mg.oritniTHERAPEUTIC DRUG MONITORING (LEVELS)omIf the patient meets ANY of the criteria below, a trough level is ndrecommended prior to the 2nd dose. A troughlevel should be obtaineda immediately before administration of a dose (i.e., 24 hours after thengprevious dose was given)sio• Concomitant nephrotoxic medications (i.e., Vancomycin, Cyclosporine, deAmphotericin B, etc.)sid• Concurrent exposure to contrast media ocy• Age ≥60 yearsogl• Patient is in the ICUn• Other risks for nephrotoxicity (e.g. diabetes, kidney transplant)miA .AInterpretation of GENTAMICIN/TOBRAMYCIN levels:Trough levelGentamicin/Tobramycin dosingrecommendation< 1 mcg/mLContinue current regimen. Repeat troughlevel weekly1–1.5 mcg/mLAccumulation may be occurring. Rechecktrough level in 24 hours> 1.5 mcg/mLUse traditional dosing methodInterpretation of AMIKACIN levels:Trough levelAmikacin dosing recommendation< 4 mcg/mLContinue current regimen. Repeat troughlevel weekly 4–6 mcg/mLAccumulation may be occurring. Rechecktrough level in 24 hours> 6 mcg/mLUse traditional dosing methodRationales for extended-interval dosing• Optimization of peak concentration/MIC ratio• Allowing for a drug-free period• Takes advantage of post-antibiotic effect (PAE) of aminoglycosides• May decrease risk of toxicity• May lower incidence of adaptive resistance• Convenience of less frequent administration• Decreased frequency of drug level monitoring• At least as efficacious as traditional dosing133ngTraditional aminoglycoside dosing and orittherapeutic drug monitoringniomDOSING • GENTAMICIN/TOBRAMYCIN: a loading dose of at least 2nda mg/kgshould be given to all patients, regardless of renal function.ng• Calculate a maintenance dosebased on CrCl, indication, andsioABW(unless patient is obese, in which case use DBWas defined at dethe beginning of the section).sid• All doses should be rounded to the nearest 10 mg.ocyIndicationoglnPneumonia/sepsis/ miPseudomonas/Other Gram-negativeA CrCl (mL/min)neutropenic feverinfections.A> 902 mg/kg Q8H2 mg/kg Q8H80–892 mg/kg Q8H2 mg/kg Q8H70–792 mg/kg Q8H1.7 mg/kg Q8H60–692.2 mg/kg Q12H2 mg/kg Q12H50–592.2 mg/kg Q12H1.7 mg/kg Q12H40–492 mg/kg Q12H1.7 mg/kg Q12H30–392.2 mg/kg Q24H2 mg/kg Q24H20–292 mg/kg Q24H1.7 mg/kg Q24H< 20 2.5 mg/kg ONCE*2 mg/kg ONCE** Give one dose, check level in 24 hours, redose when level < 2 mcg/mL• AMIKACIN: a loading dose of at least 8 mg/kgshould be given toall patients, regardless of renal function.• Calculate a maintenance dosebased on CrCl, indication, andABW(unless patient is obese, in which case use DBWas above).• All doses should be rounded to the nearest 50 mg.IndicationPneumonia/sepsis/ Pseudomonas/Other Gram-negativeCrCl (mL/min)neutropenic feverinfections> 908 mg/kg Q8H7 mg/kg Q8H80–898 mg/kg Q8H7 mg/kg Q8H70–798 mg/kg Q8H6 mg/kg Q8H60–698 mg/kg Q12H7 mg/kg Q12H50–598 mg/kg Q12H6 mg/kg Q12H40–497 mg/kg Q12H6 mg/kg Q12H30–398 mg/kg Q24H6 mg/kg Q24H20–297 mg/kg Q24H6 mg/kg Q24H< 20 10 mg/kg ONCE*8 mg/kg ONCE** Give one dose, check level in 24 hours, redose when level < 10 mcg/mL134THERAPEUTIC DRUG MONITORING (LEVELS)ngiorThere is controversy regarding aminoglycoside levels. Some argue thattnipeak levels and estimated creatinine clearance are better predictors ofomsubsequent nephrotoxicity and that trough levels add little useful information, while others believe that high trough levels are predictive ofnda nephrotoxicity. Trough levels, when used in combination with peak levels,ngare useful in calculating patient-specific dosage adjustments.sio dWhen levels should be obtained:ed• Peak and trough levels should be obtained around the 3rd dosesio• A peaklevel should be obtained 30 minutes after the end of a 30-cylminute infusion of the 3rd doseog• A troughlevel should be obtained immediately beforenadministration of the 3rd dosemiA .• Some advocate peak and trough levels after the 1st dose in patientsAwith serious infections or less predictable volumes of distribution (e.g.,patients with diffuse edema, ascites, shock, burns, or pregnantpatients). Antibiotic Management input may be of use in these cases (3-9229).• Levels should be obtained at least once a week. More frequent levelsshould be considered:• After changes in dosing regimen• If creatinine changes by 0.5 mg/dL or 30%• If there are major changes in the patient’s volume status• If the patient is not respondingDesired serum concentrations of GENTAMICIN/TOBRAMYCIN• Peak levels• Pneumonia, sepsis, Pseudomonas: 8–10 mcg/mL• Other Gram-negative infections: 6–8 mcg/mL• Trough levels• < 2 mcg/mLDesired serum concentrations of AMIKACIN• Peak levels• Pneumonia, sepsis, Pseudomonas: 25–35 mcg/mL• Other Gram-negative infections: 20–30 mcg/mL• Trough levels• < 10 mcg/mL135dosing and monitoringAminoglycoside dosing and monitoring for Gram-positive synergyDOSING• GENTAMICIN: 3 mg/kg IV once daily is recommended for treatmentof endocarditis with Viridans streptococci or S. bovisin patients withnormal renal function (CrCl ≥60 ml/min). dosing and monitoringOTOTOXICITY• Consider biweekly clinical screening for ototoxicity• Check baseline visual acuity using a Snellen pocket card• To screen for ototoxicity, have patient shake head and then re-readcard.• Concern should be raised if patient loses 2 lines of visual acuity.Consider formal audiology testing.• Contact Audiology (5-6153) for help with testing for ototoxicity e• GENTAMICIN:1 mg/kg IV Q8H is recommended for treatment of allsidother Gram-positive endocarditis infections and some cases of severeocVRE infections in patients with normal renal function (CrCl ≥60 ml/min). yoglnDosing adjustment for renal insufficiencymiACrCl (mL/min) Dosing .A40–59 1 mg/kg Q12H20–39 1 mg/kg Q24H<201 mg/kg ONCE** Give one dose, check level in 24 hours, redose when level < 1 mcg/mLNOTE:See infective endocarditis guidelines (p. 47) for duration.THERAPEUTIC DRUG MONITORING (LEVELS)• Peak and trough are recommended around the 3rd dose to assureappropriate dosing.Desired serum concentrations of GENTAMICIN• Peak levels• 3 – 5 mcg/mL• Trough levels• < 1 mcg/mLMonitoring for toxicityNEPHROTOXICITY• Serum creatinineshould be measured at least every other day. Ifcreatinine increases by 0.5 mg/dL or 30% from baseline, usetraditional dosing.• Measure serum aminoglycosidelevels with traditional dosing • Some data suggest that lowest level of nephrotoxicity occurs whenaminoglycosides are administered during the activity period (e.g.13:30), therefore afternoon administration is preferred. 136References:Aminoglycoside levels and Gram-negative pneumonia: Am J Med 1984;77:657. Daily dosing: Antimicrob Agents and Chemother 1995; 39:650.Daily dosing: Antimicrob Agents and Chemother 1999; 43:1549.Nephrotoxitiy : Antimicrob Agents and Chemother 2003; 47:1010.Gram-positive Synergy: Circulation 2005; 111(23):e394-434.Individualized pharmacokinetic dosing: Crit Care Med 1991;19:1480. edsiocyoglnmiA .A137ngiVancomycin dosing and monitoringortnioDOSINGm 1. Estimate creatinine clearance (CrCl) using Cockcroft-Gault equation:nda CrCl =(140 – age) (weight in kg)ng72 (serum creatinine*)x 0.85 (if female)sio d* For patients with low muscle mass (i.e., many patients > 65 yrs), some advocate usingna minimum value of 1 to avoid overestimation of CrClciym2. Patients who are seriously ill with complicated infections such asocnmeningitis, pneumonia, osteomyelitis, endocarditis, andabacteremiashould receive initial loading dose of 25-30 mg/kg, V.Bfollowed by 15-20 mg/kg Q8-12Hassuming normal renal functionand using Actual Body Weight (ABW). For other indications seenomogram dosing below. 3. Calculate maintenance dose (using ABW) based on estimated oractual CrCl. See suggested nomogram dosing below. Note: Younger patients with normal renal function may need higher ormore frequent dosing than suggested below.WeightCrCl (mL/min)(kg)>6030–5915–29<15 or dialysis, (HD,CVVHD)<40Consider ID/Abx Mgmt input (7-4570)40–49750 mg750 mg 750 mg1000 mg, then redose by level†Q12HQ24HQ48H50–591000 mg1000 mg 1000 mg1000 mg, then redose by level†Q12HQ24HQ48H60–751000 mg1000 mg 1000 mg1000 mg, then redose by level†Q12HQ24HQ48H76–901250 mg1250 mg 1250 mg1250 mg, then redose by level†Q12HQ24HQ48H90–1101500 mg1500 mg 1500 mg1500 mg, then redose by level†Q12HQ24HQ48H> 110Consider ID/Abx Mgmt input (7-4570)For patients with CrCl <15 mL/min and not receiving hemodialysis redose when randomlevel <15–20 mcg/mL. For patients receiving maintenance hemodialysis, redose afterhemodialysis session if pre-hemodialysis level <25 mcg/mL for pneumonia,osteomyelitis, endocarditis or bacteremia. For meningitis, consider redosing patient ifpre-hemodialysis level <30 mcg/mL.THERAPEUTIC DRUG MONITORING (LEVELS)• Peak levelsshould NOT be obtained.• Trough levelsare the most accurate and practical method formonitoring Vancomycin effectiveness and toxicity. 138Measuring serum Vancomycin levelsng• Trough levels should be obtained just prior to the next dose at steady-iorstate conditions (approximately before the 4th dose). tni• In patients with ESRD on hemodialysis, it is preferable to obtain a pre-omhemodialysis level with the routine laboratory venipuncture on the ndmorning of hemodialysis. In the event a pre-hemodialysis level is nota obtained, a post-hemodialysis level may be drawn at least six hoursngafter the dialysis session.sio• Trough levels should be considered in patients with any the following dncircumstances:ciy• Receiving aggressive dosing (>1500 mg Q12H) or Q8H intervalmo•Serious infections such as meningitis, endocarditis, osteomyelitis,cnand MRSA pneumonia.a V.• Unstable renal function (change in SCr of 0.5 mg/dL or 50% fromBbaseline) or dialysis • Concurrent therapy with nephrotoxic agents (e.g. aminoglycosides,Colistin, Amphotericin B)• Prolonged courses (>3-5 days) of therapy. • Frequency of monitoring Vancomycin trough levels: • Once-weekly monitoring is recommended for patients with stablerenal function who have achieved desired trough levels. • More frequent monitoring is recommended for patients who arehemodynamically unstable and/or with changing renal function. Desired Vancomycin trough levels• Pneumonia, osteomyelitis, endocarditis, bacteremia: 15-20 mcg/mL• CNS infections: 20 mcg/mL• Neutropenic fever, skin and skin-structure infections: 10-15 mcg/mL• For MRSA infections serum trough concentrations >10 mcg/mLshould always be maintained to avoid development of resistance.Monitoring for Toxicity • Serum creatinine should be measured at least every other day initially,then weekly if patient’s renal function remains stable. • Limited data suggest a direct causal relationship betweennephrotoxicity and higher serum trough concentrations (>15-20mcg/mL). Monitor Vancomycin trough levels (see above for frequencyand indications). • Formal audiology testing is not recommended for patients receivingVancomycin, unless signs and symptoms of ototoxicity becameapparent. References:IDSA/ASHP/SIDP Guidelines therapeutic monitoring of Vancomycin: Am J Health-SystPharm. 2009; 66; 82. ATS/IDSA Guidelines for HAP/VAP: AJRCCM 2005; 171:338. IDSA Guidelines for Bacterial Meningitis: Clin Infect Dis 2004:39:1267. 139ng,neonynygirtt)oriaaaalaaaifft,cuxooubityaittnisudnotctlrriotaeitsex,aaastttcmtsnnvoo,hyarssegtgstiaeheuroterrniftorrcphsitooaytluenopiittiihaasfevarrnncepdy7n,boolaphdr3rarmyeupenilna1alosurrtmma((uferarueesoocffiithegbg)ighsssivnntadntdggp)iislnnoteonson,)rsporiigoehoeaiirrrutnnotoaltettiigiiasoodttnnn/veenpiiivnnaactactiogsn(morara,ooitgiobidyums,eccieisnmmhyttdtdlcmrsnliiliatcrpcaeoiallineinenoraevnhcnsaapiiiecgmgmiimia,bhencenzufccoiiwwiiiznnnruiiirstthrlarlenCocfeCdollerue(cCCerunDnDntieraOsnutfAhaotefe.llsCaaoecdniiinbniidtlnocaaerr’steccnpnietyiimtadepn))iakkgthssn,iiancrhanraeoddciteencsssmoeaasnfeeeoil)dnirrnes.refccuns1iesnnl,eiiaoses65fftbeiiks-,,eas:1i,psgdtylylyeylykklykseb38lynz,eekekwa;ileemio)ryeeewaoencwwewweood4wwrfthloutlylylylylylylylylylyldsiikkkkekkkgehqukekeelylybececeeeec2k%ca200iickkeeieeesiveeeeeee–eryee05eindtreeeiennFWwTWwweet(TWWWWWWwDt(WWW1WEv↑t(Atieiecvsee(fibmtneBadeIlcnniiurtlecoiCrhg)):resutr8)oddgh2s8she,u3Kgh3t1oh13pytp1assroPnminlotegCP.er.,,eAdtiot–agnnerouptphiTlnib:ninieidenacepMetnhinn,ibnbunn–onliuroiioaitltliaasisduiiltaecetbiltneevoKnilirnriilttiti,bceclnpsbiieaeeeceabbeab/nreveeveolsluCscridtgmndenei/une/fiisgseatnnsinLTrrirLT,ngniiglisratLTilnCLTiiaNcninimtinocnbt,/AnUscsneotiaogitACf/A/aN/ATTemyooAiecna,ilyeTerrlyseT,NUgbgmCgorSLTrCBSSrBdmy,o:odloonoicr,odCSUAB,,,tAKAAlaaCcesce/A,,,,tneionsCNnieNCCddTNCCCCmBneissnaeertitoiBUenmavddSUBBBBrCaV(lysoaV(neiahncTeCBmAsUBB(BCCaaABCCCCNDaroo,rslPtmoemnoifntdtcepevilnantu,renacmfi,poxuscnsistfereodyimsuO,tamtemsksedandannenenngeenorfGpesowaer,®ansi)pli1gmonebsaleeili)tnmdnnbconililriza≥isoa)cnmralsaiociancaedso(kcceadcs,indiestiinp,oulndarnoBenlcGigitenmomypiallaeetinninig(Atmmaseinid,coocimfiraspAno,eonsftleedetonamc/PiadtrBertiiNoamcirmnncogbsSnzio,co,delPr(Aroipnuniioni:oeemnirocnicrslenlicizcetlylyestocspgnaccsliguericsegoomaaitnmydilpnnendamyhathxuniftoooreohimntipOnAastzmomyoecRnLFTubrpcecilpeaicerfifrn•••Anmmal-AToAβcMoaniCDioLRaeVVR140
Oral antimicrobial use in hospitalized patients
esualiWhen using an agent that is considered to be bioequivalent (no
obsignificant difference in rate and extent of absorption of the therapeuticcringredient) via the parenteral and oral route, the oral formulation is
mitipreferred if the patient does not have the contraindications listed below.
naalContraindications to oral therapyOr.•NPO (including medications)
D•Inability to take other oral medications OR not tolerating a liquiddiet/tube feeds
•Hemodynamic instability
•Receiving continuous NG suctioning
•Severe nausea, vomiting, diarrhea, GI obstruction, dysmotility,mucositis
•Amalabsorption syndrome
•Aconcomitant disease state that contraindicates the use of oralmedications
NOTE: There are only a limited number of agents that can beused orally for bacteremia or fungemia; these are noted inthe table below.
Bioavailability of oral antimicrobials
Antimicrobial % Oral AbsorptionShould NOT be used orally for bacteremiaAmoxicillin74 – 90%Amoxicillin/Clavulanate (Augmentin®)74 – 90%Azithromycin*38 – 83%Cephalexin 90%Cefpodoxime*41 – 50%Clindamycin 90%Doxycycline90 – 100%Tetracycline 75 – 80%Can be used orally for bacteremia or fungemiaCiprofloxacin†65 – 85%Fluconazole>90%
Linezolid†100%
Metronidazole100%
Moxifloxacin†90%
Trimethoprim/sulfamethoxazole†85 – 90%
Voriconazole‡¶~96%
*Oral absorption is enhanced in presence of food †Should not be used forS. aureusbacteremia ‡Oral absorption is decreased in presence of food¶Inter-patient variability
141
eurAntimicrobial dosing in renal failureailf Dosing recommendations can vary according to indication and patient-alnspecific parameters. All dosage adjustments are based on creatininee rnclearance calculated by Cockcroft-Gault equation. ingCrCl =(140 – age) (weight in kg)sio72 (serum creatinine*)x 0.85 (if female) d*For patients with low muscle, some advocate using a minimum of 1 to avoidalioverestimation of CrCl.ob†crIf patient is on hemodialysis (HD) schedule administration so that patientmireceives daily dose immediately AFTER dialysis. For assistance with dosagetiadjustments for patients receiving CVVHD or CVVHDF, please call pharmacy.nA .EDrugTypical dose CrCl Dose Adjustment for (may vary)(mL/min)renal insufficiency Acyclovir IV 5–10 mg/kg Q8H>505–10 mg/kg Q8H25–505–10 mg/kg Q12H10–245–10 mg/kg Q24H<10 or HD†2.5–5 mg/kg Q24HAcyclovir PO200 mg 5x daily>10200 mg 5x daily (Genital herpes)<10200 mg Q12H Acyclovir PO800 mg 5x daily>25800 mg 5x daily(Herpes Zoster) 10–25800 mg Q8H<10 or HD†800 mg Q12HAmantadine100 mg Q12H>50100 mg Q12H30–50200 mg x 1 day,then 100 mg Q24H15–29200 mg x 1 day,then 100 mg Q48H<15 or HD†200 mg weeklyAmoxicillin500–1000 mg Q12H>30500–1000 mg Q12H10–30250–875 mg Q12H<10 or HD†250–875 mg Q24HAmoxicillin1 g Q8H>301g Q8H(pneumonia)10–301g Q12H<10 or HD†1g Q24HAmoxicillin/500–1000 mg Q12H>30500–1000 mg Q12Hclavulanate10–30250–500 mg Q12H<10 or HD†250–500 mg Q24HAmphotericin B0.7–1 mg/kg Q24H–No dosage adjustmentAmBisome®3–5 mg/kg Q24H–No dosage adjustmentAmpicillin1–2 g Q4–6H >501–2 g Q4–6H10–501–2 g Q6–8H<10 or HD†1–2 g Q8HAmpicillin/1.5–3 g Q6H≥301.5–3 g Q6Hsulbactam15–291.5–3 g Q12H≤14 or HD†1.5–3 g Q24HAzithromycin250–500 mg Q24H–No dosage adjustmentAztreonam 1–2 g Q8H ≥301–2 g Q8H 10–291–2 g Q12H <10 or HD†1–2 g Q24H142DrugTypical dose CrCl Dose Adjustment for e(may vary)(mL/min)renal insufficiencyurlCefazolin1–2 g Q8H≥351–2 g Q8Haif 11–34500 mg–1 g Q12Hal<10500 mg–1 g Q24HneHD†2 g Q HD, if HD in 2 days rnOR 3g Q HD, if HD in i3 daysngCefepime1 g Q8>60 1 g Q8Hsio30–601 g Q12H d<291 g Q24HalHD†Load with 1 g, then 500 mgQ24H obiCefepime 2 g Q8H >60 2 g Q8H cr(Central nervous 30–602 g Q12H misystem infections) 11–292 g Q24Htin<11 or HD†1 g Q24HA Cefotetan1–2 g Q12H ≥301–2 g Q12H.E10–291–2 g Q24H<10 or HD†500 mg Q24HCefoxitin1–2 g Q6H >501–2 g Q6H30–501–2 g Q8–12H10–291–2 g Q12–24H<10 or HD†500 mg–1 g Q24HCefpodoxime100–400 mg Q12H≥30100–400 mg Q12H<30100–400 mg Q24HHD†100–400 mg threetimes/weekCeftazidime1–2 g Q8H>501–2 g Q8HFor Pseudomonas30–501–2 g Q12H2 g Q8H15–291–2 g Q24H5–15500 mg–1 g Q24HHD†Load with 1 g, then 500 mgQ24HCeftriaxone1–2 g Q24H–No dosage adjustmentCeftriaxone 2 g Q12H–No dosage adjustment(Central nervous system infections) Cephalexin500 mg PO Q6H >50500 mg Q6H 10–50500 mg Q8H<10 or HD†500 mg Q12HCidofovir5 mg/kg Q week for≤55 or Cr>1.5Not recommended2 weeks, then everyother weekCiprofloxacin IV400 mg Q8–12H ≥30400 mg Q8–12H <30 or HD†400 mg Q24HCiprofloxacin PO250–750 mg Q12H≥30250–750 mg Q12H<30 or HD†250–500 mg Q24HClarithromycin250–500 mg Q12H≥30250–500 mg Q12H<30250–500 mg Q24HClindamycinPO: 300 mg Q8H–No dosage adjustmentIV: 600 mg Q8HColistin 2.5 mg/kg Q12H>702.5 mg/kg Q12H(Colistimethate)25–701.25 mg/kg Q12H<25 or HD†1.5 mg/kg Q36HDaptomycin 6–10 mg/kg Q24H ≥306–10 mg/kg Q24Hfor endocarditis/<306–10 mg/kg Q48Hbacteremia HD†6–10 mg/kg Q48HDicloxacillin250–500 mg Q6H –No dosage adjustmentDoxycycline100 mg Q12H–No dosage adjustment143eDrugTypical dose CrCl (mL/min)Dose Adjustment for ur(may vary)renal insufficiencyailf Ertapenem1 g Q24H ≥301 g Q24Haln<30 or HD†500 mg Q24He10Normal dose Q24H rEthambutol15–25 mg/kg Q24H ≥n<10Normal dose Q48H iHD†Normal dose QHD sessionngFluconazole200–800 mg Q24H≥50Normal dose (e.g. 100, 400,si800 mg) Q24Ho<50 or HD†Load w/normal dose, then dal50% of normal dose Q24HiFlucytosine (5–FC)12.5–25 mg/kg Q6H>4012.5–25 mg/kg Q6Hob20–4012.5–25 mg/kg Q12Hcr10–1912.5–25 mg/kg Q24Hmi<10 or HD†12.5–25 mg/kg Q24–48HtinGanciclovir 5 mg/kg Q12H≥705 mg/kg Q12HA(Induction dose)50–692.5 mg/kg Q12H .E25–492.5 mg/kg Q24H10–251.25 mg/kg Q24H<10 or HD†1.25 mg/kg threetimes/week, administer afterHDGanciclovir 5 mg/kg Q24H≥705 mg/kg Q24H(Maintenance 50–692.5 mg/kg Q24Hdose)25–491.25 mg/kg Q24H10–250.625 mg/kg Q24H<10 or HD†0.625 mg/kg threetimes/week, administer afterHDGentamicin––See section onaminoglycoside dosingIsoniazide300 mg Q24H–No dosage adjustment Linezolid600 mg Q12H–No dosage adjustment Meropenem 1 g Q8H>511 g Q8H26–501 g Q12H10–25500 mg Q12H<10 or HD†500 mg Q24HMeropenem2 g Q8H>512 g Q8H (Central nervous 26–501 g Q8H system infections) 10–251 g Q12H<10 or HD†1 g Q24HMetronidazole500 mg Q8H–No dosage adjustmentMicafungin100–150 mg Q24H–No dosage adjustmentMoxifloxacin400 mg Q24H –No dosage adjustment Norfloxacin400 mg Q12H≥30400 mg Q12H<30 or HD†400 mg Q24HOseltamivir75 mg Q12–24H≥3075 mg Q12–24H10–2975 mg Q24–48H<10 or HD†30 mg Q every other HD sessionOxacillin1–2 g Q4–6H –No dosage adjustmentPenicillin G 3–4 million units Q4H≥503–4 million units Q4H10–501.5 million units Q4H<10 or HD†1.5 million units Q6HPiperacillin3–4 g Q6H >403 g Q6H (4 g Q6H forPseudomonas)20–403 g Q8H (4 g Q8H forPseudomonas)<203 g Q12H (4 g Q12H forPseudomonas)HD†2 g Q8H 144DrugTypical dose CrCl (mL/min)Dose Adjustment for e(may vary)renal insufficiencyurlPiperacillin/3.375–4.5 g Q6H>403.375 g Q6H (4.5 g Q6Haif tazobactamfor Pseudomonas)al20–402.25 g Q6H (3.375 g Q6H fornePseudomonas) r<20 2.25 g Q8H (2.25 g Q6H forn iPseudomonas)HD†2.25 g Q12H (2.25 g Q8H forngsiPseudomonas) oPosaconazole400 mg Q12H–No dosage adjustment dPyrazinamide15–30 mg/kg Q24H≥1015–30 mg/kg Q24Hal<1012–20 mg/kg Q24HobiHD†25–30 mg/kg QHD sessioncrQuinupristin/7.5 mg/kg Q8H –No dosage adjustmentdalfopristinmitiRifampin (TB)600 mg Q24H–No dosage adjustmentnRifampin300 mg Q8–12H–No dosage adjustmentA .Rimantadine100 mg Q12H>10100 mg Q12HE≤10100 mg Q24HTigecycline100 mg once, then –No dosage adjustment50 mg Q12H TMP/SMX PO: 1–2 DS tab Q12H≥301–2 DS tab Q12 or (UTIs or cellulitis)IV: 160–320 mg Q12H160–320 mg IV Q12H (Dosing is based on <301–2 DS tab Q24H orTMP component)160–320 mg IV Q24HTMP/SMX 5 mg/kg Q6–8H≥305 mg/kg Q6–8H (PCP or serious <302.5 mg/kg Q6–8Hsystemic infections)HD†2.5 mg/kg Q8HValacyclovir500–1000 mg Q12H≥30500–1000 mg Q12H(Genital herpes)10–29500–1000 mg Q24H<10 or HD†500 mg Q24HValacyclovir1 g Q8H≥501 g Q8H(Herpes Zoster)30–491 g Q12H10–291 g Q24H<10 or HD†500 mg Q24HValganciclovir900 mg Q12H≥60900 mg Q12H(Induction dose)40–59450 mg Q12H25–39450 mg Q24H10–24450 mg Q48H<10 or HD†Not recommendedValganciclovir900 mg Q24H≥60900 mg Q24H(Maintenance dose)40–59450 mg Q24H25–39450 mg Q48H10–24450 mg twice weekly<10 or HD†Not recommendedVancomycin––See section on vancomycindosingVoriconazoleSee Voriconazole –No dosage adjustment isguidelines page 20necessary for PO.IV should not be administeredto patients with CrCl ≤50mL/min due to accumulationof the vehicle.†If patient is on hemodialysis (HD) schedule administration so that patient receivesdaily dose immediately AFTER dialysis. For assistance with dosage adjustments forpatients receiving CVVHD or CVVHDF, please call pharmacy.145stnCost of selected antimicrobial agentseagDrugDaily dose*Cost/day** aliAmikacin1000 mg once daily$5obcrAmoxicillin500 mg three times daily$1miAmoxicillin/clavulanate500 mg three times daily$3tinAmoxicillin/clavulanate875 mg twice daily$2a Ampicillin 2 g every 4 hours$36edtcAmpicillin/sulbactam1.5 g every 6 hours$11eAzithromycin PO500 mg once daily$2els Azithromycin IV500 mg once daily$7fo tAztreonam1 g every 8 hours$96soCefazolin1 g every 8 hours$4C F.Cefepime1 g every 8 hours$15Cefotetan1 g every 12 hours$17Cefoxitin1 g every 6 hours$17Cefpodoxime200 mg twice daily$5Ceftazidime2 g every 8 hours$20Ceftriaxone1 g once daily$2Cephalexin500 mg every 6 hours$1Ciprofloxacin PO500 mg twice daily$1Ciprofloxacin IV400 mg every 12 hours$4Clarithromycin500 mg twice daily$2Clindamycin IV600 mg every 8 hours$7Clindamycin PO300 mg every 8 hours$1Daptomycin500 mg once daily$191Doxycycline100 mg twice daily$1Ertapenem1 g once daily$52Fosfomycin3 g once$36Gentamicin80 mg every 8 hours$2Gentamicin300 mg once daily$2Linezolid PO600 mg twice daily$134Linezolid IV600 mg every 12 hours$172Meropenem1 g every 8 hours$87Metronidazole PO500 mg every 8 hours$1Metronidazole IV500 mg every 8 hours$5Minocycline100 mg twice daily$1Moxifloxacin PO400 mg once daily$3Moxifloxacin IV400 mg once daily$12Nitrofurantoin100 mg twice daily$2* Estimated, based on a 70 kg patient; may vary according toindication and patient-specific parameters** Johns Hopkins Hospital acquisition cost, rounded up to nearest $1,updated 05/09146DrugDaily dose*Cost/day**stnOxacillin2 g every 4 hours$82ePenicillin G2 MU every 4 hours$12ag Piperacillin3 g every 6 hours$37aliPiperacillin/tazobactam3.375 g every 6 hours$84obcrQuinupristin/dalfopristin500 mg every 8 hours$417miRifampin PO300 mg every 8 hours$4tinRifampin IV300 mg every 8 hours$52a Tigecycline50 mg twice daily$98edtcTobramycin IV120 mg every 8 hours$6eelTMP/SMX PO1 DS tab twice daily$1s fTMP/SMX IV350 mg every 8 hours$19o tVancomycin PO125 mg four times daily$65soVancomycin IV1 g every 12 hours$10C F.* Estimated, based on a 70 kg patient; may vary according toindication and patient-specific parameters** Johns Hopkins Hospital acquisition cost, rounded up to nearest $1,updated 05/09Cost of selected antifungal agentsDrugDaily dose*Cost/day**Amphotericin B 50 mg once daily$10Liposomal AmB (AmBisome®)210 mg once daily$214Liposomal AmB (AmBisome®)350 mg once daily$357Fluconazole PO200 mg once daily$1Fluconazole IV200 mg once daily$7Fluconazole IV400 mg once daily$8Itraconazole PO (solution)200 mg once daily$19Micafungin100 mg once daily$88Micafungin150 mg once daily$132Posaconazole PO (suspension)400 mg twice daily$100Voriconazole PO200 mg twice daily$70Voriconazole IV300 mg every 12 hours$311*Estimated, based on a 70 kg patient; may vary according toindication and patient-specific parameters** Johns Hopkins Hospital acquisition cost, rounded up to nearest $1,updated 05/09147148Index~A~Abdominal infectionsBiliary tract infections . . 27-28Diverticulitis. . . . . . . . . . 28-29Pancreatitis. . . . . . . . . . 29-30Peritonitis, peritoneal dialysis-related. . . . . . . . . 34Peritonitis/GI perforation. 32-33SBP. . . . . . . . . . . . . . . 31-32Allergy, penicillin. . . . . . 118-119Amikacin. . . . . . . . . . . . . . . . . . See AminoglycosidesAminoglycosidesExtended-interval dosing 132-133Gram-positive synergy dosing. . . . . . . . . . . . . . 136Monitoring. . . . . . . . . . . . . . . . See dosing sections “Once daily dosing”. . 132-133Traditional dosing. . . . 134-135Amphotericin B, lipid. . . . . 16-17Ampicillin/sulbactam. . . . . . . . 9Antibiogram. . . . . . . . . . . 24-26Antibiotic approval form. . . . . . 6Antimicrobial dosingAminoglycosidesSee AminoglycosidesCNS infections. . . . . . . . . . 57Renal insufficiency. . . 142-145Surgical prophylaxis. . 104-107Vancomycin. . . . . . . . . . . . . . . SeeVancomycinAspergillosis. . . . . . . . . . . . . 114Aspiration pneumonia. . . . 62-66Community-acquired. . . . 62-64Healthcare-acquired. . . . 65-66~B~Biliary tract infections. . . . 27-28Bioterrorism. . . . . . . . . 130-131Bloodstream infectionsxeCatheter-related. . . . . . . 43-46ndCandida. . . . . . . . . . . . . . 99 I.0Enterococcusspp.. . . . . . 451Gram-negative rods. . . 45-46S. aureus. . . . . . . . . . . . . 44Staph, coagulase-negative44Brain abscessSee CNS infections~C~Candidemia. . . . . . . . . . . 99-101CandidiasisHematologic patient. . 115-117Non-neutropenic host. . 97-102Candiduria. . . . . . . . . . . . . 97-98Catheter-related bloodstream infections. . 43-46Cellulitis. . . . . . . . . . . . . . 79-80Central nervous system (CNS)infectionsAntibiotic dosing. . . . . . . . . 57Brain abscess. . . . . . . . . . . 56Encephalitis. . . . . . . . . . . . . 55Meningitis. . . . . . . . . . . . 53-55Shunt infection. . . . . . . . 56-57Cholangitis. . . . . . . . . . . . 27-28Cholecystitis. . . . . . . . . . . 27-28Clostridium difficile infections. . . . . . . . . . . . 35-37Colistin. . . . . . . . . . . . . . . . . . . 9Communicable diseases,reporting. . . . . . . . . . . . . . 123Combination therapy (see Double Coverage)Community-acquired pneumoniaEmpiric therapy. . . . . . . 62-63Pathogen-specific therapy. . 63COPD exacerbations. . . . . . . 61Cost of antimicrobials. . 146-147Cystic fibrosis. . . . . . . . . . 69-70149xe~D~nd I.Daptomycin. . . . . . . . . . . . . . 1001Diarrhea. . . . . . . . . . . . . . 38-40Diabetic foot infections. . . 82-84Diverticulitis. . . . . . . . . . . . 28-29Dosing, antimicrobialsSee Antimicrobial dosingDouble coverage. . . . . . 120-121~E~EncephalitisSee CNS infectionsEndocarditis. . . . . . . 47-52, 108TreatmentCulture-negative. . . . . . . . 50Diagnosis. . . . . . . . . . 51-52Fungal. . . . . . . . . . . 101-102Pathogen-specific therapy. . . . . . . . . . . 47-51Prosthetic valve. . . . . . 50-51Prophylaxis. . . . . . . . . . . . 108Endomyometritis. . . . . . . . . . 59Endophthalmitis. . . . . . . . . . 101Ertapenem. . . . . . . . . . . . 10-11~F~Febrile neutropeniaSee Neutropenic feverFormulary. . . . . . . . . . . . . . . . 8Fosfomycin. . . . . . . . . . . . 11-12Fungal infections. . . . . . 114-117Candidaspp97–102, 115-117Filamentous fungi. . . . 114-115Prophylaxis, Oncology. . . . 113Prophylaxis, SICU/WICU. . 103Fusarium. . . . . . . . . . . . . . . 115~G~GentamicinSee AminoglycosidesGI perforation. . . . . . . . . . 32-33Gonococcal urethritis, cervicitis, proctitis. . . . . . . . 59150Gynecologic infectionsEndomyometritis. . . . . . . . . 59Pelvic inflammatory disease. . . . . . . . . . . . 58-59Septic pelvic thrombophelbitis. . . . . . . . 60~H~Healthcare-acquired pneumonia (not VAP). . . . . . . . . . . . 65-66H. pyloriinfection. . . . . . . . 41-42~I~ID approvalAntimicrobials. . . . . . . . . . . . 8Forms. . . . . . . . . . . . . . . . 6-7Pager. . . . . . . . . . . . . . . . . . 7Infection control. . . . . . 122-129Infectious diarrhea. . . . . . . 38-40Influenza. . . . . . . . . . . . . . 71-72Isolation precautions. . . 124-125~L~Linezolid. . . . . . . . . . . . . . 12-13Long-term antimicrobial therapy. . . . . . . . . . . . . . . 140~M~Meningitis, bacterial. . 53-55, 57Antimicrobial dosing. . . . . . 57Empiric therapy. . . . . . . . . . 53Pathogen-specific therapy. . 54MDR Gram-negative organisms. . . . . . . . . . . . 94Micafungin. . . . . . . . . . . . 17-18Microbiology. . . . . . . . . . . 23-24MRSADecolonization. . . . . . . . 81-82Soft-tissue infections. . . . 79-80Surveillance. . . . . . . . 126-128~N~Necrotizing fasciitis. . . . . . 86-87Neutropenic fever. . . . . 111-112Nosocomial pneumonia. . . 65-68~O~OncologyNeutropenic fever. . . . 111-112Antimicrobial prophylaxis. . . . . . . . . . . 113Oral antimicrobials. . . . . . . . 141~P~Pancreatitis. . . . . . . . . . . . 29-30Parasites. . . . . . . . . . . . . . . . 40Pelvic inflammatory disease58-59Pelvic thrombophlebitis. . . . . . 60Penicillin allergy. . . . . . . 118-119Peritonitis/GI perforation. . 32-33Peritoneal dialysis-related. . . 34Spontaneous bacterial. . 31-32Post-op / post-procedureinfections. . . . . . . . . . 84-86PneumoniaCommunity-acquired. . . . 62-64Healthcare-acquired. . . . 65-66Ventilator-associated. . . . 66-68Posaconazole. . . . . . . . . . 18-20Pre-operative prophlyaxis105-107Price of antimicrobials. . 146-147Prophylactic use of antimicrobialsEndocarditis. . . . . . . . . . . 108Fluconazole in ICUs. . . . . . 103Oncology. . . . . . . . . . . . . 113Pre-op / pre-procedure105-107Solid organ. . . . . . . . 109-110~R~Renal insufficiencyAntimicrobial dosing. . 142-145Reported diseases. . . . . . . . 123Resistant Gram-negativexeinfections. . . . . . . . . . . . 93-95ndRestricted antimicrobials. . . . . . 8 I.01~S~SBPSee PeritonitisSepsis in ICU. . . . . . . . . . . . . 77Sexually transmitted diseases (PID). . . . . . . . 58-59Shunt infectionSee CNS infectionsSkin and soft-tissue infectionsCellulitis. . . . . . . . . . . . . 79-80Cutaneous abscess. . . . 80-81Diabetic foot infection. . . 82-84Necrotizing fasciitis. . . . 86-87Post-op infections. . . . . . 84-86Recurrent MRSA. . . . . . . 81-82Surgical-site infections. . 84-86Surgical prophylaxis. . . 104-107Surgical-site infections. . . . 84-86Prevention. . . . . . . . . . . . . 129SurveillanceMRSA. . . . . . . . . . . . 126-127VRE. . . . . . . . . . . . . . 127-128Susceptibility testing. . . . . 23-24Synergy. . . . . . . . . . . . . . . . 120~T~Thrombophlebitis. . . . . . . . . . 60Therapeutic monitoringAminoglycosides. . . . 132-137Vancomycin. . . . . . . . 138-139Outpatient long-termantimicrobial therapy. . . 140Tigecycline. . . . . . . . . . . . 13-14Tobramycin See AminoglycosidesTransplantAntimicrobial prophylaxis109-110Tuberculosis. . . . . . . . . . . . 71-76151xe~U~nd I.Urinary tract infections01BacterialCystitis. . . . . . . . . . . . 89-90Pyelonephritis. . . . . . . 89-90Urosepsis. . . . . . . . . . 89-90Catheter-Associated. . . . 91-92Fungal. . . . . . . . . . . . . . . . 97-98~V~VancomycinDosing. . . . . . . . . . . . . . . 138Guidelines. . . . . . . . . . . 14-15Monitoring. . . . . . . . . 138-139Ventilator-associated pneumonia (VAP). . . . . . . . . . . . . . . 66-68Voriconazole. . . . . . . . . . . 20-22VRE Surveillance. . . . . . 127-128~W~Wound infections, post-op. 84-86152setoN153Important Phone Numbers Antibiotic Approval:. . . . . . . . . . . . . . 3-9ABX (3-9229)Antibiotic Management Program:. . . . . . . . . . . . 7-4570Infectious Diseases Consults:. . . . . . . . . . . . . . . 3-8026Tucker Service (Transplant ID). . . . . . . . . . . . . #4-0242Osler 2 Pharmacy:. . . . . . . . . . . . . . . . . . . . . . . 5-6150Carnegie 6 Pharmacy:. . . . . . . . . . . . . . . . . . . . 5-6505Weinberg Pharmacy:. . . . . . . . . . . . . . . . . . . . . 5-8998Microbiology Lab:. . . . . . . . . . . . . . . . . . . . . . . 5-6510Hospital Epidemiology & Infection Control:. . . . . . 5-8384HEIC Emergency Beeper:. . . . . . . . . . . . . . . . . . 3-3855The Johns Hopkins HospitalAntibiotic Management ProgramIntranet: www.insidehopkinsmedicine.org/ampInternet: www.hopkinsmedicine.org/ampOsler 425(443) 287-4570 (7-4570)© Copyright 2009 by The Johns Hopkins Hospital AntibioticManagement Program. 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