title: Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms.
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.
authors: Division of Pharmacotherapy, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors: Alicia M
authors: AM
authors: Reese
authors: Christopher R
authors: CR
authors: Frei
authors: David S
authors: DS
authors: Burgess
mesh_terms: D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007260:Infusion Pumps; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D000077725:Piperacillin, Tazobactam Drug Combination; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D002511:Cephalosporins; D000077725:Piperacillin, Tazobactam Drug Combination; D000077723:Cefepime; D010397:Penicillanic Acid; D001618:beta-Lactamases; D010878:Piperacillin