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Title: Ceftolozane/Tazobactam Resistance and Mechanisms in Carbapenem-Nonsusceptible Pseudomonas aeruginosa
Authors: Teo, Jocelyn Qi-Min
Lim, Jie Chong
Tang, Cheng Yee 
Lee, Shannon Jing-Yi
Tan, Si Hui
Sim, James Heng-Chiak
Ong, Rick Twee-Hee 
Kwa, Andrea Lay-Hoon 
Keywords: ceftolozane/tazobactam
molecular characterization
Pseudomonas aeruginosa
Issue Date: 24-Feb-2021
Publisher: American Society for Microbiology
Citation: Teo, Jocelyn Qi-Min, Lim, Jie Chong, Tang, Cheng Yee, Lee, Shannon Jing-Yi, Tan, Si Hui, Sim, James Heng-Chiak, Ong, Rick Twee-Hee, Kwa, Andrea Lay-Hoon (2021-02-24). Ceftolozane/Tazobactam Resistance and Mechanisms in Carbapenem-Nonsusceptible Pseudomonas aeruginosa. mSphere 6 (1) : 1-Sep. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: This study established the in vitro activity of ceftolozane/tazobactam (C/T) and its genotypic resistance mechanisms by whole-genome sequencing (WGS) in 195 carbapenem-nonsusceptible Pseudomonas aeruginosa (CNSPA) clinical isolates recovered from Singapore between 2009 and 2020. C/T susceptibility rates were low, at 37.9%. Cross-resistance to ceftazidime/avibactam was observed, although susceptibility to the agent was slightly higher, at 41.0%. Whole-genome sequencing revealed that C/T resistance was largely mediated by the presence of horizontally acquired b-lactamases, especially metallo-b-lactamases. These were primarily disseminated in well-recognized high-risk clones belonging to sequence types (ST) 235, 308, and 179. C/T resistance was also observed in several non-carbapenemase-producing isolates, in which resistance was likely mediated by b-lactamases and, to a smaller extent, mutations in AmpC-related genes. There was no obvious mechanism of resistance observed in five isolates. The high C/T resistance highlights the limited utility of the agent as an empirical agent in our setting. Knowledge of local molecular epidemiology is crucial in determining the potential of therapy with novel agents. © 2021 Teo et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Source Title: mSphere
ISSN: 2379-5042
DOI: 10.1128/msphere.01026-20
Rights: Attribution 4.0 International
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