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High-Dose Ampicillin-Sulbactam Combinations Combat Polymyxin-Resistant Acinetobacter baumannii in a Hollow-Fiber Infection Model

2017; American Society for Microbiology; Volume: 61; Issue: 3 Linguagem: Inglês

10.1128/aac.01268-16

1098-6596

Justin R. Lenhard, Nicholas M. Smith, Zackery P. Bulman, Xun Tao, Visanu Thamlikitkul, Beom Soo Shin, Roger L. Nation, Jian Li, Jürgen B. Bulitta, Brian T. Tsuji,

Phenothiazines and Benzothiazines Synthesis and Activities

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.