High-Dose Ampicillin-Sulbactam Combinations Combat Polymyxin-Resistant Acinetobacter baumannii in a Hollow-Fiber
Justin R Lenhard1,2,3, Nicholas M Smith1,2, Zackery P Bulman1,2
1Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.
Abstract:
Acinetobacter baumannii is emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 108 CFU/ml of two clinical A. baumannii isolates resistant to all three drugs (maximum reductions, 1.6 and 3.1 logs). In a 14-day hollow-fiber infection model, high-dose ampicillin-sulbactam (8/4 g every 8 h, respectively) in combination with meropenem (2 g every 8 h) and polymyxin B (1.43 mg/kg of body weight every 12 h with loading dose) resulted in rapid (96 h) eradication of A. baumannii.
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