Susceptibilities of cefiderocol, meropenem-xeruborbactam, cefepime-taniborbactam, aztreonam-avibactam, and sulbactam-durlobactam against imipenem-non-susceptible Gram-negative bacilli in Taiwan
Year: 2025
Type: article
Abstract: Objectives To evaluate susceptibilities of novel antibiotics against imipenem-non-susceptible 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 PCR. 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 bla OXA-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 bla IMP alone, whereas reduced AZA activity was linked to PBP3 alteration or bla CMY-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.
Authors: Yan-Ru Wang, Yu-Lin Lee, Mei-Chen Tan, Pei-Jing Chen, I-Wen Huang, Jui-Fen Lai, Hui-Ying Wang, Yih-Ru Shiau, Shu-Chen Kuo, Ya-Sung Yang
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,900
Funders: National Science and Technology Council, Tungs' Taichung MetroHarbor Hospital, Cathay General Hospital, Chang Gung Medical Foundation, Kaohsiung Medical University, National Health Research Institutes, National Cheng Kung University Hospital, Shionogi, Far Eastern Memorial Hospital, Changhua Christian Hospital, National Cheng Kung University, Taichung Veterans General Hospital, Sin-Lau Hospital, Tri-Service General Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taipei Veterans General Hospital, Kaohsiung Veterans General Hospital, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Kaohsiung Armed Forces General Hospital, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, National Science and Technology Council, Centers for Disease Control and Prevention, Kaohsiung Chang Gung Memorial Hospital, Taiwan Centers for Disease Control
Awards: G1648766588, Investigation of in Vitro and in Vivo Efficacies of Novel Β-Lactamase Inhibitors in Combination with Cefepime against Elizabethkingia Species and the Potential Resistance Mechanism, G3412989694, G3428492055, Investigation of Resistance Mechanisms of Β-Lactams in Elizabethkingia Spp.; 1. Characterization of a Novel Β-Lactamase and 2. Researches on the Resistance Mechanisms for Cefiderocol, G8257498618, G8387235602, G8472848442
OpenAlex ID: W4416972002