Abstract
Pseudomonas aeruginosa is one of the most important pathogens in cystic fibrosis. In this study we analysed the genetic basis and phylogenetic profile of resistance to ceftazidime/avibactam and ceftolozane/tazobactam as well as carbapenems in cystic fibrosis P. aeruginosa isolates. We conducted whole genome sequence analysis of a collection of isolates resistant to piperacillin/tazobactam 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 amino acid variations in AmpC were associated with high-level ceftazidime resistance not reversed by cloxacillin. 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. Critically, we show that mutational resistance emerged in phylogenetically distant lineages suggesting that the mutations occur independently without conferring a selective advantage to any phylogenetic lineage. Our findings confirm the strong contribution of mutation-driven evolution to the population structure of P. aeruginosa.
Original language | English |
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Pages (from-to) | 774-780 |
Number of pages | 7 |
Journal | International Journal of Antimicrobial Agents |
Volume | 53 |
Issue number | 6 |
Early online date | 2 Mar 2019 |
DOIs | |
Publication status | Published - Jun 2019 |
Keywords
- Pseudomonas aeruginosa
- cystic fibrosis
- ceftazidime/avibactam
- ceftolozane/tazobactam
- ampC
- AmpD
- oprD
- mutation-driven evolution
- Ceftolozane/tazobactam
- Cystic fibrosis
- Ceftazidime/avibactam
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Profiles
-
Karolin Hijazi
- School of Medicine, Medical Sciences & Nutrition, Dental Education - Senior Clinical Lecturer
- Institute of Medical Sciences
- Clinical Medicine
Person: Clinical Academic