Abstract
INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat in oncology settings due to its multidrug resistance and ability to form biofilms on indwelling medical devices. METHODS: This study investigated the in vitro and in vivo activity of meropenem/vaborbactam (MEV) against two CRKP isolates recovered from catheter-related bloodstream infections in patients undergoing orthopedic oncologic surgery. RESULTS: Whole-genome sequencing identified the isolates as ST101 and ST307, harboring resistance determinants including bla(KPC-3) and bla(OXA-1) , distributed across IncFII and IncFIB plasmid replicons. Both isolates exhibited extensive resistance to β-lactams, aminoglycosides, and fluoroquinolones but remained susceptible to MEV. Phenotypic assays revealed enhanced biofilm formation and metabolic activity compared to the reference strain Kp ATCC 13883 in the absence of hypervirulence-associated genes. MEV demonstrated bactericidal activity against both planktonic and biofilm-associated cells, with minimum bactericidal concentration (MBC(90)) and minimum biofilm eradication concentration (MBEC(90)) values of 0.5/8 μg/ml for CRKP ST101, 0.12/8 μg/ml for CRKP ST307, and 0.25/8 μg/ml for the Kp ATCC 13883 strain. In the Galleria mellonella infection model, MEV significantly improved larval survival following the CRKP challenge. DISCUSSION: These findings demonstrate that MEV exhibits activity against planktonic and biofilm-associated CRKP cells and highlight the need for further investigation in managing catheter-related bloodstream infections caused by multidrug-resistant K. pneumoniae.