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Title: Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients.
Authors: Zamudio, Roxana
Hijazi, Karolin
Joshi, Chaitanya
Aitken, Emma
Oggioni, Marco R.
Gould, Ian M.
First Published: 2-Mar-2019
Publisher: Elsevier for International Society of Chemotherapy
Citation: International Journal of Antimicrobial Agents, 2019, 53 (6), pp. 774-780
Abstract: Pseudomonas aeruginosa is one of the most important pathogens in cystic fibrosis. This study was conducted to analyse the genetic basis and phylogenetic profile of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in cystic fibrosis P. aeruginosa isolates. Whole genome sequence analysis was conducted of isolates resistant to piperacillin/tazobactam collected from seven hospitals in Scotland since the introduction of these two cephalosporin/β-lactamase inhibitor combinations. Ceftazidime resistance was primarily related to AmpC induction, as tested by cloxacillin inhibition assays, while high-level ceftazidime resistance not reversed by cloxacillin was associated with amino acid variations in AmpC. Only isolates resistant to both ceftazidime/avibactam and ceftolozane/tazobactam carried AmpD mutations, likely resulting in ampC overexpression. All isolates resistant to ceftazidime/avibactam and/or ceftolozane/tazobactam were resistant to carbapenems and showed inactivating mutations in the chromosomal oprD gene. None of the isolates bore class A, B, D plasmid-encoded carbapenemases. This study showed that mutational resistance emerged in phylogenetically distant lineages, which indicates the mutations occur independently without conferring a selective advantage to any phylogenetic lineage. These findings confirm the strong contribution of mutation-driven evolution to the population structure of P. aeruginosa.
DOI Link: 10.1016/j.ijantimicag.2019.02.022
eISSN: 1872-7913
Embargo on file until: 2-Mar-2020
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © Elsevier for International Society of Chemotherapy 2019. After an embargo period this version of the paper will be an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.ijantimicag.2019.02.022
Appears in Collections:Published Articles, Dept. of Genetics

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