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

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 C ss/MIC ratio (where C ss is the concentration at steady state) was ≥2 for all continuous infusion (CI) regimens. MIC 50, MIC 90 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.