Abstract
The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum beta-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, 64/4mug/mL, 1024/4mug/mL and 33\% for piperacillin/tazobactam and 8mug/mL, 16mug/mL and 0\% for cefepime. For piperacillin/tazobactam, 3.375g every 4h (q4h) achieved the highest probability of target attainment (43\%), followed by 13.5g CI (31\%), 3.375g q6h (27\%), 4.5g q8h (17\%) and 6.75g CI (10\%). However, for cefepime, 4g CI had the highest probability of target attainment (77\%), followed by 1g q8h (65\%), 2g q12h (58\%), 3g CI (46\%) and 1g 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.
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