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.
Keywords: MexCD-OprJ; Pseudomonas aeruginosa; ceftolozane-tazobactam; efflux pumps.
【저자키워드】 Pseudomonas aeruginosa, MexCD-OprJ, ceftolozane-tazobactam, efflux pumps., 【초록키워드】 Treatment, whole-genome sequencing, Mutation, Azithromycin, Sequencing, specificity, COVID-19 infection, Patient, Missense mutation, mutant, inhibitor, Combination, Pseudomonas aeruginosa, strain, Ventilator-associated pneumonia, nonsense mutation, carbapenem, meropenem, wild-type, construction, Modification, tazobactam, cephalosporin, avibactam, ceftolozane, caused, evidenced, periplasmic, Pseudomona, 【제목키워드】 resistance, emergence, novel, Pseudomonas aeruginosa, pump, efflux,