Imipenem: a potent inducer of multidrug resistance in Acinetobacter baumannii

Han-Yueh Kuo1, Kai-Chih Chang, Jai-Wei Kuo

  • 1Department of Medicine, National Taiwan University Hospital-Hsin-Chu Branch, Hsin-Chu City, Taiwan.

Insights

Imipenem exposure strongly promotes multidrug resistance in Acinetobacter baumannii. This resistance involves carbapenemase and efflux pump mechanisms, highlighting the need for careful carbapenem antibiotic use.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Acinetobacter baumannii is a significant opportunistic pathogen.
  • Multidrug resistance (MDR) in A. baumannii poses a major global health threat.
  • Carbapenem antibiotics are crucial for treating A. baumannii infections.

Purpose of the Study:

  • To investigate how imipenem exposure influences the development of multidrug resistance in Acinetobacter baumannii.
  • To identify the resistance mechanisms involved in imipenem-induced MDR.
  • To compare imipenem's MDR induction potential with other antibiotics.

Main Methods:

  • Generation of imipenem-selected and other antibiotic-selected mutant strains of A. baumannii.
  • Phenotypic antibiotic susceptibility testing with and without efflux pump inhibitors (NMP, CCCP).
  • Analysis of antimicrobial resistance gene expression profiles.

Main Results:

  • Imipenem was a potent inducer of MDR in reference A. baumannii strains compared to other tested antibiotics.
  • Imipenem-selected mutants exhibited altered expression of OXA-51-like carbapenemase, efflux pumps, and AmpC β-lactamase.
  • Efflux pump inhibitors (NMP, CCCP) partially reversed imipenem and amikacin resistance in selected mutants and clinical isolates.

Conclusions:

  • Imipenem can act as a strong inducer of multidrug resistance in A. baumannii.
  • The combination of OXA-51-like carbapenemase and other resistance mechanisms contributes to MDR.
  • Close monitoring of carbapenem usage is essential to curb the spread of MDR A. baumannii in healthcare settings.

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