In Vitro Activity of Imipenem/Relebactam and Ceftolozane/Tazobactam Against Multidrug-Resistant Klebsiella pneumoniae: A Retrospective Single-Center Study in China

Background: Multidrug-resistant Klebsiella pneumoniae (MDR-KP) is a global health threat with limited treatment options. Comparative in vitro data for imipenem-relebactam (I/R) and ceftolozane-tazobactam (C/T) across diverse MDR-KP clinical populations remain limited. Methods: Susceptibility to I/R and C/T was determined by Etest. Whole-genome sequencing was used to identify sequence types, resistance genes, and virulence genes, with hypervirulent K. pneumoniae (hvKP) defined by genomic criteria. Results: A total of 312 nonduplicate MDR-KP clinical isolates, including 70.8% carbapenem-resistant K. pneumoniae (CR-KP), 56.7% difficult-to-treat resistant K. pneumoniae (DTR-KP), and 28.2% carbapenem-resistant hvKP (CR-hvKP), were retrospectively analyzed. I/R resistance was low across all subgroups (overall 3.8%, CR-KP 5.0%, DTR-KP 6.2%, CR-hvKP 2.3%) and across specimen types (0–9.6%; blood 3.8%). In contrast, C/T resistance was higher (overall 57.7%, CR-KP 79.2%, DTR-KP 91.0%, CR-hvKP 84.1%), with the highest rate in respiratory isolates (63.0%), followed by blood (57.7%) and urine (50.0%). Among extended-spectrum β-lactamase (ESBL)-producing isolates, I/R and C/T resistance rates were 2.1% and 12.4%, respectively. Although C/T resistance was higher in hvKP than in classic K. pneumoniae in unadjusted analysis, hvKP was not independently associated with increased C/T resistance after adjustment. Instead, ST11, ST15, ST307, blaKPC-2, and blaNDM-1 were independently associated with C/T resistance. For I/R, blaNDM-1 was associated with resistance. Conclusions: I/R was active across MDR-KP subgroups including CR-hvKP and DTR-KP. C/T worked mainly against ESBL-producers. These findings highlight the importance of resistance genotyping when interpreting susceptibility to these agents.