Association of doripenem resistance with OXA-type carbapenemases in Acinetobacter baumannii isolates

Objectives:

To evaluate the in vitro activity of doripenem in Acinetobacter baumannii (A. baumannii) clinical isolates that possess different OXA-type carbapenemases, and to evaluate the roles of these enzymes in the development of carbapenem resistance.

Methods:

This retrospective study was conducted with 25 A. baumannii isolates at Sakarya University Training and Research Hospital, Sakarya, Turkey from June to October 2014. Antibiotic susceptibility testing was carried out using the Vitek-2 automated system (bioMérieux, Marcy l’Etoile, France). Minimum inhibitory concentrations (MICs) were determined using Etest strips (bioMérieux, Marcy l’Etoile, France). Quantitative polymerase chain reaction was performed in a Fluorion Instrument (Iontek, Istanbul, Turkey).

Results:

Isolates were divided into 5 groups based on their susceptibility profiles and OXA-type carbapenemase positivity. Group 2 isolates whose MIC of both meropenem and doripenem are in the range of 4-32 µg/mL were negative for both bla_OXA-23 and bla_OXA-58. Group 3 isolates whose MIC of meropenem and doripenem is in the range of 4-32 µg/mL, bla_OXA-23 is positive, and bla_OXA-58 is negative. Group 5 isolates whose MIC of meropenem is >32 µg/mL, and that of doripenem is in the range of 16-32 µg/mL were positive for both bla_OXA-23 and bla_OXA-58.

Conclusion:

The bla_OXA-23 and bla_OXA-58 gene combinations may confer resistance with a much greater MIC of both meropenem and doripenem. However, the presence of bla_OXA-58 alone was not correlated with doripenem resistance.The rise of antibiotic resistance is an increasingly important threat, particularly for infections caused by Acinetobacter baumannii (A. baumannii). The use of carbapenems to treat A. baumannii infection has resulted in outbreaks of infection with carbapenem-resistant Acinetobacterspp.1 We are now faced with more problematic drug-resistant pathogens that threaten to move us into what some consider the post-antibiotic era of infectious diseases. Regardless, a potential strategy is to focus on the relation of molecular characterization of the isolates and the response to antimicrobial theraphy.2 Carbapenem resistance in Acinetobacterspp. has been ascribed to the recruitment and production of carbapenem-hydrolyzing class D β-lactamases (CHDLs), and to a lesser extent metallo-β-lactamases. In A. baumannii, the CHDLs can be intrinsic (OXA-51-like), or acquired (OXA-23-like, OXA-24-like, and OXA-58-like).3 Although these enzymes weakly hydrolyze carbapenems, they can confer strong resistance when bla_OXA genes are overexpressed, as a result of their association with mobile elements, such as ISAba1, which carries a strong promoter.4 The bla_OXA-23 gene, in association with ISAba1 is spread by A. baumannii worldwide, and is the most prevalent OXA allele in isolates from Turkey.3,5 However, the carbapenem against, which antibiotic resistance emerges according to OXA gene status is unknown. The purpose of this study was to evaluate the in vitro activity of doripenem in a collection of A. baumannii clinical isolates that possess different OXA-type carbapenemases, and to evaluate the roles of these enzymes in the development of carbapenem resistance.