Reviewed by: Jose Lucar, MD, The George Washington University
Bottom line: Detection of β-lactamases is not sufficient to predict K. pneumoniae resistance to major β-lactams agents, and additional diagnostic tools capable of detecting other key resistance mechanisms (i.e., AmpCs, porin loss) are needed.
An important limitation of antibiotic resistance gene detection is the potential discrepancy with phenotypic susceptibility testing of a bacterial isolate. In this study, Maclean and colleagues aimed to determine the relative contribution of β-lactamases (SHV, ESβLs, AmpCs) and outer membrane porin loss on the resistance profile of 20 clinical Klebsiella pneumoniae isolates. Clinical isolates were characterized by whole genome sequencing (WGS), and resistance determinants were evaluated by real-time polymerase chain reaction (rtPCR) and western blots. Key results include the association of chromosomal SHV expression and ceftolozane/tazobactam non-susceptibility, the loss of outer membrane porins predicted ertapenem and meropenem non-susceptibility, and the presence of plasmid-encoded β-lactamases (either AmpC or ESβL) in the setting of porin loss was significantly associated with third generation cephalosporin, ceftolozane/tazobactam, and meropenem resistance. Taken together, these results show that detection of β-lactamases alone was not enough to predict K. pneumoniae resistance to all β-lactams tested, and additional diagnostic tools capable of detecting other key resistance mechanisms (i.e., AmpCs, porin loss) are needed.
Reference:
Maclean AKW, Morrow S, Niu F, Hanson ND. What Contributes to the MIC? Beyond β-Lactamase Gene Detection in Klebsiella pneumoniae. J Infect Dis. Published online April 24, 2024. doi:10.1093/infdis/jiae204