In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain

J Antimicrob Chemother. 2004 Feb;53(2):393-5. doi: 10.1093/jac/dkh080. Epub 2004 Jan 16.

Abstract

Objectives: The potential therapeutic role of meropenem combined with sulbactam against a clinical endemic isolate of multidrug-resistant Acinetobacter baumannii, Ab-153, was investigated.

Methods: The antimicrobial susceptibility of Ab-153 to various drugs was studied by the agar dilution method and Etest strips. The antibacterial activity of meropenem and sulbactam were investigated by a time-kill study in vitro and further examined for therapeutic efficacy in vivo in a murine model.

Results: In the time-kill study, at a concentration of 0.5 x MIC (4 mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only the combination demonstrated bactericidal effects and there was at least a 5 log(10) reduction in bacterial colony counts after 48 h, compared with either drug alone. BALB/c mice infected with 2.1-2.6 x 10(7) cfu of Ab-153 were treated with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in combination. The survival rate of mice in the combination group was significantly higher than that in the meropenem-treated or sulbactam-treated group (87% versus 35%, P = 0.0004; 87% versus 30%, P = 0.0002).

Conclusions: Meropenem in conjunction with sulbactam can exhibit more potent antimicrobial activity against Ab-153 than meropenem or sulbactam alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Meropenem
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Sulbactam / pharmacology*
  • Sulbactam / therapeutic use*
  • Survival Analysis
  • Thienamycins / pharmacology*
  • Thienamycins / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Thienamycins
  • Meropenem
  • Sulbactam