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

Antimicrob Agents Chemother. 2017 Feb 23;61(3):e01268-16. doi: 10.1128/AAC.01268-16. Print 2017 Mar.

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.

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / growth & development
  • Ampicillin / blood
  • Ampicillin / pharmacokinetics
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Body Mass Index
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Dosage Calculations
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Humans
  • Meropenem
  • Microbial Sensitivity Tests
  • Models, Statistical*
  • Polymyxin B / blood
  • Polymyxin B / pharmacokinetics*
  • Sulbactam / blood
  • Sulbactam / pharmacokinetics
  • Thienamycins / blood
  • Thienamycins / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Thienamycins
  • sultamicillin
  • Ampicillin
  • Meropenem
  • Polymyxin B
  • Sulbactam