In Vitro Activity of Doripenem in Combination With Various Antimicrobials Against Multidrug-Resistant Acinetobacter Baumannii: Possible Options for the Treatment of Complicated Infection

Microb Drug Resist. 2013 Oct;19(5):407-14. doi: 10.1089/mdr.2012.0250. Epub 2013 May 9.

Abstract

Aims: The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay.

Results: Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods.

Conclusions: This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / growth & development
  • Acinetobacter baumannii / isolation & purification
  • Amikacin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use*
  • Colistin / therapeutic use
  • Doripenem
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Intensive Care Units
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives
  • Minocycline / therapeutic use
  • Tertiary Healthcare
  • Tigecycline

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Tigecycline
  • Amikacin
  • Doripenem
  • Minocycline
  • Colistin