Molecular Mechanisms Underlying Carbapenem-Resistant Acinetobacter baumannii (CR-AB) in Tel-Aviv

Background:

Oxacillinases (OXAs) and metallo β-lactamases (MBLs) are major mechanisms of CR in AB with varying prevalence in different locales. CR-AB is endemic in many Israeli hospitals and follows a complex epidemiological pattern, but the mechanisms underlying CR are unknown.  

Objective: To elucidate the molecular mechanisms underlying CR-AB in the Metropolitan Tel-Aviv area.

Methods: A representative sample of clinical CR-AB isolates (n=59) recovered between 2003 and 2008 in our hospital (8-11 strains/year) was studied. CR-AB was identified by VITEK-2 GN-ID and GN059 cards (BioMerieux, Marcy l’Etoile, France). CR was confirmed by the E-test (AB biodisk, Solna, Sweden) per CLSI breakpoints. Strains were screened for the presence of OXAs/MBLs by PCR performed with primers designed to amplify 4 OXA groups (OXA-23-like / 24-like / 51-like / 58-like) and MBLs (IMP, VIM, SIM groups).  Amplicons were analyzed visually by gel staining and representative amplicons of appropriate size were sequenced and then aligned using the BLAST software. Clonal relatedness of study isolates was assessed using REP-PCR.   
Results: The MIC₅₀/MIC₉₀ of imipenem and meropenem were all above 32µg/ml. Study strains belonged to multiple genetic clones and no single clone predominated. None of the isolates produced MBL enzymes. All strains carried at least one OXA gene; OXA-51-like genes (including OXA-66) were detected in 57 strains (97%), OXA-23- or OXA-24-like genes were detected in 52 strains (88%), being mainly OXA-23 or OXA-72, and OXA-58-like was detected in 8 strains (13.5%). While OXA-51 / 23 / 24-like elements were found in strains spanning all study years, OXA-58 was found only in strains from 2003 and 2008. Three strains (5%) were “triple-OXA” positive, combining OXA-23, 51 and 58 or OXA-23, 51 and 72.

Conclusions: CR-AB isolates in Tel-Aviv were associated with at least one OXA gene  but not MBLs. OXA-51-like genes were present in most strains (including OXA-66) and OXA-23/24-like genes were also highly prevalent. OXA-58 which is common in Europe was detected occasionally in selected years, while OXA-23/24-like elements have emerged. Notably, 5% of strains were “triple-OXA” positive. The distribution of different OXAs over time coincides with the clonal diversity of CR-AB and represents an infection control challenge.