The Mechanism of High-Level Carbapenem Resistance in Klebsiella pneumoniae: Underlying Ompk36-Deficient Strains Represent a Threat of Emerging High-Level Carbapenem-Resistant K. pneumoniae with IMP-1 β-Lactamase Production in Japan

The mechanisms of high-level carbapenemresistance in Klebsiella pneumoniae isolated in Japan were investigated. High-level carbapenem-resistant K. pneumoniae Mkp4437 and a less carbapenem-sensitive K. pneumoniae strain, Mkp4365, were recovered from the same patient. These two strains were found to be homologous by pulsed-field gel electrophoresis, and both strains contained blaIMP-1, blaDHA-1, blaCTXM-14, blaTEM-1, and blaSHV-1. Based on the sodium dodecyl sulfate–polyacrylamide gel electrophoresisanalysis, the lack of Ompk36 was observed in Mkp4437. Direct sequencing of the ompK36 gene demonstrated that a new insertional sequencein the open reading frame of the ompK36 gene was found in Mkp4437. Three clinical isolates ( minimum inhibitory concentration[MIC] 2–4 mg/L to imipenem) were identified upon screening the strains of K. pneumoniae isolated in the University hospital with MICs of ≥1 mg/L to imipenem. Interestingly, these three isolates all lacked OmpK36. Conjugation of the plasmid harboring IMP-...