Pharmacodynamic model for β-lactam regimens used in surgical prophylaxis: model-based evaluation of standard dosing regimens.

Abstract

Background Continual evolution of resistance among bacteria against methods of surgical prophylaxis may make currently used beta-lactam regimens inadequate. Objective To re-evaluate beta-lactamregimensin surgical prophylaxis. Setting A pharmacodynamic Monte Carlo simulation (MCS) modelbased on a number of patients in China. Methods Pharmacodynamic profiling using Monte Carlo simulation up to 4hours postinfusion was conducted for standard-dose, short-term (0.5h) and prolonged (2 to 4h) infusions of ampicillin, cefazolin, cefotaxime, cefoxitin, cefuroxime, ertapenem, and piperacillin/tazobactam in adult patients with normal renal function. Microbiological data were incorporated. Cumulative fraction of response (CFR) was determined for each regimen against populations of S. aureus, coagulase-negative staphylococci and E. coli. The optimal CFR was defined as ≥ 90% response. Main Outcome Measure Cumulative fractions of responseof pharmacodynamic target attainment. Results During the first 2hours postinfusion, piperacillin/tazobactam 3.375g exhibited consistently optimal cumulative fractions against S. aureus, CoNS and E. coli. Ampicillin 2g (2h) also displayed optimal CFRs for S. aureus and E. coli but not for coagulase-negative staphylococci. Cefoxitin 2g didnot achieve any optimal CFRs, even via 2-h prolonged infusion (maximum 72.8% CFR for S. aureus and 64.5% CFR for E. coli). Cefazolin 2g (4h) and cefuroxime 1.5g (4h) provided desired CFRs across 4h postinfusion for S. aureus but provided poor CFRs for coagulase-negative staphylococci and E. coli. Only ertapenem 1g for E. coli and S. aureus and cefotaxime 1g for E. coli consistently yielded ≥ 90% CFRs for 4hour postinfusion. Conclusions Certain dosing regimens may warrant adjustment for improved prevention efficiency and enhanced empirical antibiotic regimens for surgical prophylaxis.