Prevention of rifampicin resistance in Acinetobacter baumannii in an experimental pneumonia murine model, using rifampicin associated with imipenem or sulbactam

J Antimicrob Chemother. 2006 Sep;58(3):689-92. doi: 10.1093/jac/dkl303. Epub 2006 Jul 26.


Objectives: To examine the development of rifampicin resistance in multidrug-resistant Acinetobacter baumannii exposed to rifampicin and the prevention of the appearance of rifampicin-resistant mutants when rifampicin is used in association with imipenem or sulbactam.

Methods: A clinical strain of multidrug-resistant A. baumannii was used to examine the frequency of resistance to rifampicin in vivo, in a pneumonia model in immunocompetent C57BL/6 mice. The in vitro and in vivo prevention of the development of resistance to rifampicin was analysed using rifampicin alone or in association with imipenem or sulbactam, in time-kill studies and in the experimental murine pneumonia, respectively.

Results: Rifampicin-resistant mutants were found at 48 and 72 h, both in vitro and in vivo, when rifampicin was used alone, with the MIC increasing from 4 to > or =128 mg/L. The in vivo frequency of rifampicin-resistant mutants was 3 x 10(-6). On the contrary, no resistant mutants appeared after 72 h, in vitro or in vivo, when rifampicin was employed in association with imipenem or sulbactam. After six daily passages in rifampicin-free agar plates the resistant mutants maintained the high resistance to rifampicin (> or =128 mg/L).

Conclusions: These results suggest that rifampicin must not be used alone in the treatment of infections caused by multidrug-resistant A. baumannii. In these cases, rifampicin may be used in combination with imipenem or sulbactam, which prevent the development of resistance to rifampicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii* / drug effects
  • Acinetobacter baumannii* / genetics
  • Acinetobacter baumannii* / growth & development
  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Therapy, Combination
  • Female
  • Imipenem / administration & dosage
  • Imipenem / pharmacology
  • Imipenem / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Mutation
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Rifampin* / administration & dosage
  • Rifampin* / pharmacology
  • Rifampin* / therapeutic use
  • Sulbactam / administration & dosage
  • Sulbactam / pharmacology
  • Sulbactam / therapeutic use


  • Anti-Bacterial Agents
  • Imipenem
  • Sulbactam
  • Rifampin