Predictability of doripenem susceptibility in Acinetobacter baumannii isolates based on other carbapenem susceptibilities and blaOXA gene status

John S. Esterly, Chao Qi, Michael Malczynski, Marc H. Scheetz

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Study Objective. To better define the utility of surrogate markers for doripenem susceptibility relative to gold standard microbiology tests. Design. In vitro experiment. Setting. Large tertiary-care academic medical center. Organisms. One hundred twenty-five randomly selected, unique clinical isolates of Acinetobacter baumannii collected between 2005 and 2008. Measurements and Main Results. In vitro activity of doripenem, imipenem, and meropenem was examined by agar dilution, and the carbapenem-hydrolyzing oxacillinase gene, blaOXA, status was determined by polymerase chain reaction for clinical isolates of A. baumannii. Positive predictive values for doripenem susceptibility were evaluated according to imipenem susceptibility, meropenem susceptibility, the doripenem Etest, and blaOXA gene status. Imipenem had the greatest activity against all A. baumannii isolates tested (51% susceptible), followed by meropenem and doripenem (44% and 29% susceptible, respectively). The positive predictive value for doripenem susceptibility was 68% with meropenem susceptibility by agar dilution, 56% with imipenem susceptibility by agar dilution, and 82% with the doripenem Etest. Doripenem Etest susceptibilities yielded eight major errors when compared with agar dilution. The blaOXA genes were present in 52 isolates (42%). Expression of either blaOXA-23 or blaOXA-40 was 100% predictive of resistance to doripenem, imipenem, and meropenem. In isolates not harboring blaOXA genes, 49% were susceptible to doripenem. Among the 125 isolates, carbapenem discordance existed in 22% (28 isolates), all of which were susceptible to imipenem but not to doripenem. Conclusion. In the A. baumannii isolates tested in this study, the doripenem Etest resulted in eight susceptibility misclassifications yet remained the most accurate predictor of doripenem susceptibility. The blaOXA genes in A. baumannii appeared to confer resistance against doripenem, imipenem, and meropenem and may be the best existing surrogate marker to accurately predict resistance to these drugs. Further study is necessary to better characterize the full genotypic carbapenem resistance profile of A. baumannii relative to newer carbapenem agents, such as doripenem.

Original languageEnglish (US)
Pages (from-to)354-360
Number of pages7
JournalPharmacotherapy
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2010

Keywords

  • Acinetobacter baumannii
  • bla
  • Carbapenem-hydrolyzing oxacillinase genes
  • Carbapenems
  • Doripenem
  • Susceptibility

ASJC Scopus subject areas

  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Predictability of doripenem susceptibility in Acinetobacter baumannii isolates based on other carbapenem susceptibilities and bla<sub>OXA</sub> gene status'. Together they form a unique fingerprint.

  • Cite this