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Phylogenetic Analysis of Resistance to ceftazidime/avibactam, ceftolozane/tazobactam and Carbapenems in piperacillin/tazobactam-resistant Pseudomonas Aeruginosa From Cystic Fibrosis Patients

Roxana Zamudio, Karolin Hijazi, Chaitanya Joshi, Emma Aitken, Marco R Oggioni, Ian M Gould

Int J Antimicrob Agents. 2019 Jun;53(6):774-780.

PMID: 30831233

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP23598723 Cloxacillin Related Compound D Cloxacillin Related Compound D 23598-72-3 Price
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