Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum β-lactamase-producing organisms

Alicia M. Reese, Christopher R. Frei, David S. Burgess

    Research output: Contribution to journalArticle

    29 Scopus citations

    Abstract

    The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum β-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N = 39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T > MIC) for the intermittent bolus regimens was ≥40% for piperacillin/tazobactam and ≥60% for cefepime. The desired Css/MIC ratio (where Css is the concentration at steady state) was ≥2 for all continuous infusion (CI) regimens. MIC 50, MIC90 and %S were, respectively, 64/4 μg/mL, 1024/4 μg/mL and 33% for piperacillin/tazobactam and 8 μg/mL, 16 μg/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375 g every 4 h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5 g CI (31%), 3.375 g q6h (27%), 4.5 g q8h (17%) and 6.75 g CI (10%). However, for cefepime, 4 g CI had the highest probability of target attainment (77%), followed by 1 g q8h (65%), 2 g q12h (58%), 3 g CI (46%) and 1 g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.

    Original languageEnglish (US)
    Pages (from-to)114-119
    Number of pages6
    JournalInternational Journal of Antimicrobial Agents
    Volume26
    Issue number2
    DOIs
    StatePublished - Aug 1 2005

    Keywords

    • Cefepime
    • Extended-spectrum β-lactamase
    • Pharmacodynamics
    • Piperacillin/tazobactam

    ASJC Scopus subject areas

    • Microbiology (medical)
    • Infectious Diseases
    • Pharmacology (medical)

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