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.
Keywords:
Acinetobacter; antibiotic resistance; antimicrobial combinations; meropenem; polymyxins; sulbactam; synergism.
Copyright © 2017 American Society for Microbiology.
MeSH terms
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Acinetobacter Infections / drug therapy
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Acinetobacter Infections / microbiology
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Acinetobacter baumannii / drug effects*
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Acinetobacter baumannii / growth & development
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Ampicillin / blood
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Ampicillin / pharmacokinetics
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Anti-Bacterial Agents / blood
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Anti-Bacterial Agents / pharmacokinetics*
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Area Under Curve
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Biological Availability
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Body Mass Index
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Drug Administration Schedule
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Drug Combinations
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Drug Dosage Calculations
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Drug Resistance, Multiple, Bacterial
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Drug Synergism
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Humans
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Meropenem
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Microbial Sensitivity Tests
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Models, Statistical*
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Polymyxin B / blood
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Polymyxin B / pharmacokinetics*
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Sulbactam / blood
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Sulbactam / pharmacokinetics
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Thienamycins / blood
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Thienamycins / pharmacokinetics*
Substances
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Anti-Bacterial Agents
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Drug Combinations
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Thienamycins
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sultamicillin
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Ampicillin
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Meropenem
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Polymyxin B
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Sulbactam