In vitro activity of doripenem against Acinetobacter baumannii clinical isolates

Sara Marti1, Javier Sánchez-Céspedes, Verónica Alba

  • 1Servei de Microbiologia, Centre de Diagnòstic Biomèdic, Hospital Clínic, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.

Insights

Doripenem shows superior in vitro activity against Acinetobacter baumannii strains with the bla(OXA-58) gene compared to imipenem and meropenem. Isolates with the bla(OXA-24) gene were resistant to all tested carbapenems.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Acinetobacter baumannii is a significant cause of hospital-acquired infections.
  • Carbapenem resistance in A. baumannii is a growing global health concern.
  • Carbapenemases, such as OXA-type enzymes, are key mechanisms of resistance.

Purpose of the Study:

  • To evaluate the in vitro activity of doripenem against clinical isolates of Acinetobacter baumannii.
  • To compare doripenem's efficacy with imipenem and meropenem, particularly in relation to specific carbapenemase genes.
  • To assess the impact of bla(OXA-58) and bla(OXA-24) genes on doripenem susceptibility.

Main Methods:

  • In vitro susceptibility testing of doripenem, imipenem, and meropenem against 87 Acinetobacter baumannii clinical isolates.
  • Detection and characterization of carbapenemase genes, including bla(OXA-58) and bla(OXA-24).
  • Determination of minimum inhibitory concentrations (MICs) for each antibiotic against the isolates.

Main Results:

  • Doripenem demonstrated superior in vitro activity against A. baumannii isolates harboring the bla(OXA-58) gene compared to imipenem and meropenem.
  • Isolates expressing the bla(OXA-24) gene were resistant to doripenem, imipenem, and meropenem.
  • A lower percentage of bla(OXA-58) positive isolates exhibited high-level doripenem resistance (MIC >8 µg/mL) than with imipenem or meropenem.

Conclusions:

  • Doripenem offers a potential therapeutic advantage over imipenem and meropenem for treating A. baumannii infections mediated by the bla(OXA-58) carbapenemase.
  • The presence of bla(OXA-24) confers resistance to doripenem, imipenem, and meropenem, highlighting the importance of genotypic resistance detection.
  • These findings underscore the need for susceptibility testing to guide antibiotic selection for A. baumannii infections.