Gomis-Font MA; Pitart C; Del Barrio-Tofiño E; Zboromyrska Y; Cortes-Lara S; Mulet X; Marco F; Vila J; López-Causapé C; Oliver A
Abstract:
A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. Through the construction of mexD mutants and complementation assays with wild-type nfxB, it was evidenced that resistance to the novel cephalosporin-β-lactamase inhibitor combinations was caused by the modification of MexD substrate specificity.
Antimicrobial agents and chemotherapy:
2021
doi: 10.1128/AAC.00089-21
https://pubmed.ncbi.nlm.nih.gov/34060900
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