Imipenem heteroresistance induced by imipenem in multidrug-resistant Acinetobacter baumannii: Mechanism and clinical implications

Hao Yuan Lee, Chyi Liang Chen, Shi Bo Wang, Lin Hui Su, Shu Hung Chen, Shu Ying Liu, Tsu Lan Wu, Tzou Yien Lin, Cheng Hsun Chiu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Acinetobacter baumannii has emerged as a major pathogen causing nosocomial infections, particularly in critical patients admitted to the Intensive Care Unit. Increasing resistance to carbapenems in A. baumannii has been observed worldwide. Here we report the clinical impact and mechanism of imipenem heteroresistance (imipenem minimum inhibitory concentration of 6-32 μg/mL with the presence of resistant cells inside the inhibition zone of Etest strips or disks) in multidrug-resistant A. baumannii (MDR-AB). To identify risk factors associated with the emergence of imipenem heteroresistance, a retrospective case-control study was undertaken involving cases with subsequent clinical isolates of the same genotype showing loss of imipenem susceptibility and matched controls with isolates belonging to imipenem-susceptible MDR-AB. The molecular mechanism of heteroresistance was examined. From April 2006 to March 2007, 126 consecutive isolates of MDR-AB were identified from 29 patients. Switch from imipenem susceptibility to heteroresistance was more likely to occur in successive MDR-AB derived from patients who had been exposed to imipenem (length of use 10.9 ± 6.5 days for cases vs. 5.3 ± 4.8 days for controls; P = 0.02). An insertion sequence (ISAba1) was found in the promoter region of a class C β-lactamase gene (blaADC-29) in most imipenem-heteroresistant MDR-AB isolates. In vitro experiments indicated that imipenem heteroresistance, which was associated with overexpression of bla ADC-29, could be induced by imipenem. Carbapenem use was the only risk factor identified for the emergence of carbapenem-heteroresistant MDR-AB. Physicians should weigh the benefits and risks of each carbapenem-based treatment in managing carbapenem-susceptible MDR-AB infection.

Original languageEnglish
Pages (from-to)302-308
Number of pages7
JournalInternational Journal of Antimicrobial Agents
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

Keywords

  • Acinetobacter baumannii
  • Carbapenem
  • Heteroresistance
  • Imipenem
  • Multidrug resistance

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Imipenem heteroresistance induced by imipenem in multidrug-resistant Acinetobacter baumannii: Mechanism and clinical implications'. Together they form a unique fingerprint.

  • Cite this