The purpose of this study was to analyse the β-lactam resistance phenotype associated with common transmissible bla genes 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. A group of 30 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 that a porin (particularly, OmpK36) -defective K. pneumoniae strain may become carbapenem non-susceptible upon acquisition of ordinary ESBL genes. Sequencing of ompK36 genes and sodium dodecyl-sulphate-polyacrylamide gel electrophoresis demonstrated loss or mutations in all isolates in which reduced susceptibility to ertapenem (MIC >1mg/L) was evident in the absence of known “carbapenemase” genes (n=23). For this reason, it is crucial to detect these mutations in K. pneumoniae strains to ensure the success of antimicrobial therapy.