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

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-lactam regimens in surgical prophylaxis. Setting A pharmacodynamic Monte Carlo simulation (MCS) model based on a number of patients in China. Methods Pharmacodynamic profiling using Monte Carlo simulation up to 4 hours postinfusion was conducted for standard-dose, short-term (0.5 h) and prolonged (2 to 4 h) 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 response of pharmacodynamic target attainment. Results During the first 2 hours postinfusion, piperacillin/tazobactam 3.375 g exhibited consistently optimal cumulative fractions against S. aureus, CoNS and E. coli. Ampicillin 2 g (2 h) also displayed optimal CFRs for S. aureus and E. coli but not for coagulase-negative staphylococci. Cefoxitin 2 g 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 2 g (4 h) and cefuroxime 1.5 g (4 h) provided desired CFRs across 4 h postinfusion for S. aureus but provided poor CFRs for coagulase-negative staphylococci and E. coli. Only ertapenem 1 g for E. coli and S. aureus and cefotaxime 1 g for E. coli consistently yielded ≥ 90% CFRs for 4 hour postinfusion. Conclusions Certain dosing regimens may warrant adjustment for improved prevention efficiency and enhanced empirical antibiotic regimens for surgical prophylaxis.