Insertion Sequence-Dependent <i>OmpK</i>36 Mutation Associated Ertapenem Resistance in Clinical <i>Klebsiella pneumoniae</i>

Abstract

Extended-spectrum β-lactamases (ESBLs) and/or AmpC enzymes combined with deficiency of porins OmpK35 and OmpK36 are important for the development of carbapenem-resistant Klebsiella pneumoniae. We characterized the clinical K. pneumoniae human isolates and investigated the effect of meropenem induction on the ompK35 and ompK36 mutation to develop carbapenem resistance from six carbapenem-susceptible ESBL-producing K. pneumoniae strains. 163 clinical K. pneumoniae isolates were grouped mostly into the ESBL + AmpC (44.2%) and ESBL (42.9%) phenotypes. The resistance rate differed between cephalosporins (52.1% for cefepime -97.5% for cefotaxime) and carbapenems (16% for meropenem -28.2% for imipenem) (P < 0.001). The ESBL group showed the lowest resistance to cefoxitin and cefepime and all carbapenems, whereas the AmpC group exhibited the lowest resistance to cefepime and the highest resistance to all carbapenems. PCR amplification identified bla TEM , bla SHV , bla CTX-M-3-like , and bla CTX-M-14-like of AmpA β-lactamase genes and bla DHA and bla CMY of AmpC β-lactamase genes. Compared to all 163 clinical isolates, the 56 carbapenem-resistant isolates carried less frequently of bla TEM , bla CTXM-14-like , and bla CTXM-3-like and more frequently of bla DHA-1 and bla C-MY-2 . The carbapenem-resistant isolates differed in prevalence against imipenem, ertapenem, and meropenem and lacked OmpK35 more frequently than OmpK36, but abnormal PCR amplicons were detected fewer in the Omp K35-deficient group than in the OmpK36-deficient group (32.5% vs. 68.4%,