Klebsiella pneumoniae is a leading cause of hospital acquired
infection such as pneumonia, they are resistant to almost all antibiotics
including the carbapenems which are often regarded as antibiotic of ʽlast
resortʼ in critical infections. The aim of this study was to investigate the
natural MIC distribution of β-lactam resistance phenotypes and the molecular
mechanisms of carbapenem resistance in Klebsiella
pneumoniae in Sydney, Australia. A total of 180 clinical isolates, with
relevant transmissible resistance genes (plasmid AmpC, n=28; Extended spectrum
β-lactamase, n=72 or carbapenemase, n=50), were characterised. Thirty Klebsiella pneumoniae isolates with no phenotypic resistance to any
antibiotics tested and none of the important β-lactam genes were also included
as controls. The minimal inhibitory concentrations (MIC) of five β-lactam
antibiotics (cefotaxime, ceftazidime, imipenem, meropenem and ertapenem) against
these isolates were found to be normally distributed in the bacterial
population, except ertapenem. We found a high prevalence of ETP non-susceptibility
among the blaCTX-M isolates
(20/72, 28%) and this was due to the combination of the ESBL gene with an
OmpK36 defect. Sequencing of ompK36
genes and sodium dodecyl-sulphate-polyacrylamide gel electrophoresis
demonstrated loss or mutations in the ompK36
gene in all isolates with reduced susceptibility to ertapenem (MIC >1 mg/l) in
the absence of known “carbapenemase” genes (n=23). This means that a porin
(particularly, OmpK36) -defective K.
pneumoniae strain may become carbapenem non-susceptible upon acquisition of
ordinary ESBL genes. For this reason, it is crucial to detect these mutations
in K. pneumoniae strains to ensure
the success of antimicrobial therapy.