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Mechanisms of Carbapenem Resistance in K.pneumoniae and E. coli from Bloodstream Infections in India

Archa Sharma, Yamuna Devi Bakthavatchalam, Radha Gopi, Shalini Anandan, Valsan Philip Verghese and Balaji Veeraraghavan

Introduction: Emergence and global spread of carbapenemase producing Enterobacteriaceae (CPE) are of great concern in healthcare settings. Resistance to carbapenem is mostly conferred by metallo β-lactamase (IMP, VIM and NDM) and carbapenem hydrolyzing class D β-lactamase (OXA-48 like). The aim of this study was to characterise the molecular mechanism of resistance in the clinical isolates of Enterobacteriaceae causing bacteremia and showing resistance to β-lactams, including carbapenems.

Materials and Methods: Isolates of E.coli (n=42) and K. pneumoniae (n=134) from blood culture collected during 2013-2015 were screened for carbapenemase production by using carba NP test and the presence of carbapenem resistant genes (KPC, IMP, VIM, NDM and OXA- 48 like). Sequencing was performed for the randomly selected isolates positive for NDM and OXA-48 like.Results: Of the 176 isolates, 97% of the isolates were found to be positive with carba NP test. Carba NP test has the sensitivity, specificity, PPV and NPV of 98%, 50%, 99% and 20% respectively. Each of blaNDM and blaOXA-48 like was seen in 32% of the tested isolates. Co-production of blaNDM and blaOXA48 like and blaVIM and blaOXA48 were seen in 13% and 8% of isolates respectively. Noticeably, 3% of isolates were identified as co-producers of blaNDM, blaVIM and blaOXA48 like. All of the sequenced NDM and OXA-48 like were identified as NDM-1 and OXA-181 variants.

Conclusion: Increasing incidence of OXA-48 like is worrisome in developing countries. Because of its weak hydrolytic acivity against broad spectrum cephalosporin and carbapenems, these may go undetected in routine screening. In particular, blaOXA48 like gene is mostly identified on the plasmid and is implicated as the cause for silent spread and outbreaks in hospitalized patients.