Optimising antibiotic dosing regimens based on pharmacodynamic target attainment against Pseudomonas aeruginosa...

Owing to increasing resistance rates in Europe, pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Pseudomonas aeruginosa isolated in Hungary. Minimum inhibitory concentrations for 180 non-duplicate P. aeruginosa collected from 14 hospitals in Hungary were determined by Etest methodology. A 5000-subject Monte Carlo simulation was performed to calculate the bactericidal cumulative fraction of response (CFR) for standard dosing regimens of cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam. In the case of poor CFR, alternative dosage regimens were simulated for selected agents by increasing the infusion time, dose and frequency. Owing to high resistance rates in Hungary, no regimen achieved >90% CFR. CFRs for standard dosing regimens were: meropenem 1g every 8h (q8h), 77.1%; ceftazidime 2g q8h, 75.3%; imipenem 0.5 g every 6h (q6h), 71.7%; and piperacillin/tazobactam 4.5 g and 3.375 g q6h, 72.4% and 71.0%, respectively. Ciprofloxacin achieved significantly lower bactericidal CFRs than any beta-lactam. Prolonged infusion regimens improved the CFR for cefepime, imipenem, meropenem and piperacillin/tazobactam. Overall, the highest CFR (88.1%) was achieved by a 3-h infusion of meropenem 2g q8h. Given the poor CFR predicted with standard dosage regimens against these isolates, it seems prudent to consider alternative dosage strategies such as increasing doses, frequencies or infusion times as well as combination therapy when empirically treating infections caused by P. aeruginosa in Hungary.