11. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis. ClinInfect Dis. 2009;48:503-35.12. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of Aspergillosis: clinical practice guidelines of the InfectiousDiseases Society of America. Clin Infect Dis. 2008;46:327-352.13. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of Blastomycosis:2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1802-1812.14. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcaldisease: 2010 update by the Infections Diseases Society of America. Clin Infect Dis. 2010;50:000-000.
University of Wisconsin Hospital and Clinics<strong>UW</strong>HC <strong>Guidelines</strong> For the <strong>Use</strong> of Prolonged Infusions of Beta-LactamsPlease address questions, comments, and suggestions regarding this guideline toSara Shull, Manager, Drug Policy Program at 608/262-1817.<strong>Guidelines</strong> developed by <strong>UW</strong>HC Center for Drug PolicyAuthor: Jeffrey Fish, PharmD, Brian Moilien, PharmD candidateUpdated by: Lucas Schulz, PharmDReviewed by: Barry Fox, MD, Sarah Bland, RPh, Jeffrey Fish, PharmD <strong>Antimicrobial</strong>Subcommittee, Pharmacokinetic CommitteeCoordination: Lee Vermeulen, M.S., Director, CDPApproved by P&T:Update:A. Principles and BackgroundB. ObjectivesC. GuidelineD. Dose of AntibioticE. ReferencesA. Principles and BackgroundAs a result of continuously developing antimicrobial resistance and a shortage of novelantimicrobial development, new dosing strategies have been proposed to optimize thepharmacodynamics of existing antimicrobials. <strong>Antimicrobial</strong> activity can be separated into twobroad categories: time-dependent or concentration-dependent killing. Time-dependentantimicrobials demonstrate maximum efficacy when the percent of time above the minimuminhibitory concentration (%T>MIC) is optimized. The efficacy of concentration-dependentantimicrobials is dependent on the ratio of the area under the concentration-time curve and theminimum inhibitory concentration (AUC/MIC). Piperacillin/tazobactam, cefepime and meropenemall exhibit time-dependent killing. Theoretically, prolonged and continuous infusions of betalactamsshould increase the time of antimicrobial exposure above the MIC and, as a result,improve their efficacy. Prolonged infusions have beneficial effects over continuous infusionsincluding not needing a dedicated line/catheter and usually using a lower total daily dose.Piperacillin/TazobactamKim et al. used a Monte Carlo simulation model of serum concentration-time profiles at steadystate for piperacillin/tazobactam dosed by prolonged infusion regimens, conventional intermittentdosing regimens and continuous infusions. 1 The probability of achieving 50% unbound timeabove the MIC (fT>MIC) for 470 P. aeruginosa isolates with intermittent dosing was 74.7%(3.375g every 6 hours), 79.9% (4.5g every 6 hours), and 85.6% (4.5g every 4 hours). Forprolonged infusions, probability of 50% fT> MIC was 83.3% (3.375g every 8 hours; 4-hourinfusion), 87.1% (4.5g every 8 hours; 4-hour infusion), and 89.6% (4.5g every 6 hours; 3-hourinfusion). For continuous infusions, probability of 50% fT>MIC was 82.3% for 10.125 g/day,86.5% for 13.5 g/day and 90% for 20 g/day. Prolonged and continuous infusions achievedcumulative fractions of response and probabilities of target attainment greater than thoseobserved with a 30 minute intermittent infusion. However, prolonged infusions of 3.375g every 8hours given over 4 hours achieved 50% fT>MIC in 92.8%, 40.1% and 2.7% of patients at MICs of16, 32, and 64 mcg/ml, respectively.Lodise et al. compared mortality rates and median length stay for patients receiving prolongedinfusion (over 4 hours) versus conventional infusion (over 30 minutes) of piperacillin/tazobactamin a retrospective cohort study of patients with documented P. aeruginosa infection. 2 Patientswere excluded if the P. aeruginosa was documented as being intermediate or resistant to
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PREFACEThe Antimicrobial Use Guidel
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Antimicrobial Cost Table (Cost info
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Summary of Antibiotic Order Form: S
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LUNGS/PULMONARYCommunity-Acquired P
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PART I: BY DRUGABACAVIRFor up-to-da
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constructed systemic-pulmonary shun
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AMPICILLIN/SULBACTAM (Unasyn ® )Us
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ATOVAQUONE/PROGUANIL (Malarone ® )
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CEFAZOLINUsual DoseAdult: Moderate/
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CommentsDose adjustment required fo
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1. Typhoid fever. (NOTE: Third-gene
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-Dutasteride-Eltrombopag-Theophylli
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CLINDAMYCINUsual DoseAdult: 600-900
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DAPTOMYCINInfectious Disease approv
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Concurrent administration with peni
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• Cisapride (contraindicated) •
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• Oral contraceptives/hormones -
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Synergy in infective endocarditis a
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• Colchicine • Indinavir • Ta
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• Donepezil • Pioglitazone• D
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with linezolid should be considered
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4. Life-threatening Gram-negative i
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MOXIFLOXACINLevofloxacin and moxifl
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Indications1. Uncomplicated cystiti
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CommentsDose adjustment required fo
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PIPERACILLIN/TAZOBACTAM (Zosyn ® )
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PRIMAQUINEUsual DoseAdult: Malaria
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RIFABUTINUsual DoseAdult (150 mg ca
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• Chloramphenicol • Leflunomide
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SULFISOXAZOLENo longer available as
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TICARCILLIN/CLAVULANATE (Timentin
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2. Recurrent urinary tract infectio
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VANCOMYCINUsual DoseAdult: 1 g Q12H
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Careful monitoring of patients usin
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APPENDIX B: UWHC SURGICAL ANTIMICRO
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GI:Appendectomy 3Anaerobic organism
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VascularLIKELYPATHOGENS• ANTIMICR
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Cleanorthopedicprocedures(other)Sta
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APPENDIX C: THERAPY FOR TUBERCULOSI
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p-Aminosalicylic acid(PAS)Granules
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Appendix D: UNIVERSITY OF WISCONSIN
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Appendix E: UWHC Guidelines for the
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