Pharmacodynamic profiling of optimal sulbactam regimens against carbapenem-resistant Acinetobacter baumannii for critically ill patients

Objective: To study the minimum inhibitory concentration (MIC) of sulbactam against carbapenem-resistant Acinetobacter baumannii (CR-AB) and to determine the dosage regimens reaching target time of free drug concentration remaining above the MIC (fT>MIC). Methods: Clinical isolates of CR-AB from patients admitted to Phramongkutklao Hospital, Thailand from January 2014 to December 2015 were obtained. The MIC of sulbactam for each CR-AB isolate was determined using the agar dilution method. Each sulbactam regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) in critically ill patients. PTA was defined by how likely a specific drug dose was to reach 40% and 60% fT>MIC. The CFR was the probability of drug dose covering the MIC range of CR-AB. Dosing regimens reaching above 80% of PTA and CFR, were considered as the optimal dosage for documented and empirical therapy, respectively. Results: A total of 118 CR-AB isolates were included in the study. The percentile at the fiftieth and ninetieth MIC of sulbactam were 64 and 192 μg/mL, respectively. For a MIC of sulbactam of 4 μg/mL, all dosage regimens achieved PTA target. However, only a sulbactam dosage of 12 g intravenous daily using 2-4 h infusion or continuous infusion that covered for isolates with a sulbactam MIC of 96 μg/mL, met the PTA or CFR targets. Conclusions: The MIC of sulbactam against CR-AB is quite high. The sulbactam dose of 12 g/day using prolonged infusion was required to achieve the target fT>MIC for CR-AB treatment