Susceptibilities of cefiderocol, meropenem-xeruborbactam, cefepime-taniborbactam, aztreonam-avibactam, and sulbactam-durlobactam against imipenem-non-susceptible Gram-negative bacilli in Taiwan.

OBJECTIVES: To evaluate susceptibilities of novel antibiotics against imipenem-non-susceptible (INS) Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB), Pseudomonas aeruginosa (INS-PA) in Taiwan, and the potential resistance mechanisms.

METHODS: The minimum inhibitory concentrations of 387 INS isolates (2020-2022) were determined by broth microdilution. Resistance genes were detected using multiplex polymerase chain reaction. Whole genome sequencing and plasmid curing were conducted to identify potential resistance mechanisms.

RESULTS: Cefiderocol showed >90% susceptibility across all species. The susceptibilities of meropenem-xeruborbactam (XEM), cefepime-taniborbactam (FTB), and aztreonam-avibactam (AZA) were 72-96% for 29 INS-EC; 95-97% for 138 INS-KP; and 0-95% for 135 INS-AB; and 32-70% for 85 INS-PA. Sulbactam-durlobactam (SUD) was active against 93% of INS-AB. Cefiderocol, XEM, and AZA retained >80% activity against class B carbapenemase-producing INS-EC/KP. Cefiderocol, XEM, and SUD showed >90% activity against blaOXA-23/24-like INS-AB. Reduced FTB activity in INS-EC was associated with both YRIK/YRIN insertion in penicillin-binding protein 3 (PBP3) and carbapenemase genes or blaIMP alone, whereas reduced AZA activity was linked to PBP3 alteration or blaCMY-42. CONCLUSIONS: Cefiderocol was highly effective, whereas novel β-lactam/β-lactamase inhibitors activity varied by species and carbapenemase types. PBP3 alterations reduced FTB and AZA activity in INS-EC.