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

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, bla_OXA, 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 bla_OXA 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 bla_OXA genes were present in 52 isolates (42%). Expression of either bla_OXA-23 or bla_OXA-40 was 100% predictive of resistance to doripenem, imipenem, and meropenem. In isolates not harboring bla_OXA 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 bla_OXA 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.