Evaluation of antibacterial activities of flomoxef against ESBL producing Enterobacteriaceae analyzed by Monte Carlo Simulation

The growing number of infection caused by extended-spectrum β-lactamase (ESBL) producing pathogens has prompted a more rational use of available antibiotics because of the paucity of new, effective agents. Flomoxef (FMOX) is one of the β-lactam antibiotic which is stable against β-lactamase. In this study, the antibacterial activity of FMOX was investigated, and Monte Carlo Simulation was conducted to determine the appropriate dosing regimens of FMOX based on the probability of target attainment (TA%) at the critical drug exposure metric of time that drug concentrations remain above 40% (showing bacteriostatic effect) or 70% (showing bactericidal effect) of time during which plasma concentration above minimum inhibitory concentration (MIC) of the drug (T>MIC) against the ESBL producing Enterobacteriaceae. The effective regimens to achieve 80% of TA% at 70% of T>MIC were 1g every 8 hours with 2–4 hours infusion, and 1g every 6 hours with 1–4 hours infusion. Moreover, all the tested regimens were effective to achieve 80% of TA% at 40% of T>MIC. These results of pharmacokinetics/pharmacodynamics (PK/PD) modeling showed the potential efficacy of FMOX against bacterial infections caused by ESBL producing Enterobacteriaceae.