Pharmacodynamic Effects of Sulbactam/Meropenem/Polymyxin-B Combination Against Extremely Drug Resistant Acinetobacter...

The aims of the study are to evaluate the activity of sulbactam, meropenem, and polymyxin B alone and in combination against six isolates of extremely drug resistant Acinetobacter baumannii and to determine dosing regimens that achieve a sufficient joint probability of target attainment (PTA) based on combination antimicrobial pharmacodynamics. The combinations were evaluated by the checkerboard method and were considered synergistic when the fractional inhibitory concentration index (FICI) ≤0.5. Pharmacodynamic analyses were carried out by evaluating dosing regimens that achieve ≥90% joint PTA at the percentage of time over a 24-h period wherein the free drug concentration is above the minimum inhibitory concentration (%fT> MIC) of 40% and 60% for meropenem and sulbactam, respectively, and 20 for the ratio of the area under the free drug concentration-time curve over MIC (fAUC/MIC) for polymyxin B. For both polymyxin B-resistant and susceptible isolates, the addition of sulbactam in combination with meropenem and subinhibitory concentration of polymyxin B showed important synergistic activity (five isolates; FICI ≤0.281); the recommended dosing regimens were 2/4 g meropenem/sulbactam q8 hours and 0.5 mg/kg polymyxin B q12 hours. This in vitro study showed that sulbactam can significantly improve the action of meropenem and polymyxin B in OXA-producing A. baumannii isolates, especially when there are no new treatment options available for infections caused by these microorganisms.