Association of Ibla/I[sub.VIM-2], Ibla/I[sub.PDC-35], Ibla/I[sub.OXA-10,] Ibla/I[sub.OXA-488] and Ibla/I[sub.VEB-9] β-Lactamase Genes with Resistance to Ceftazidime–Avibactam and Ceftolozane–Tazobactam in Multidrug-Resistant IPseudomonas aeruginosa/I

Ceftazidime–avibactam and ceftolozane–tazobactam are approved for the treatment of complicated Gram-negative bacterial infections including multidrug-resistant (MDR) Pseudomonas aeruginosa. Resistance to both agents has been reported, but the underlying mechanisms have not been fully explored. This study aimed to correlate β-lactamases with phenotypic resistance to ceftazidime–avibactam and/or ceftolozane–tazobactam in MDR-P. aeruginosa from Qatar. A total of 525 MDR-P. aeruginosa isolates were collected from clinical specimens between 2014 and 2017. Identification and antimicrobial susceptibility were performed by the BD Phoenix[sup.TM] system and gradient MIC test strips. Of the 75 sequenced MDR isolates, 35 (47%) were considered as having difficult-to-treat resistance, and 42 were resistant to ceftazidime–avibactam (37, 49.3%), and/or ceftolozane–tazobactam (40, 53.3%). They belonged to 12 sequence types, with ST235 being predominant (38%). Most isolates (97.6%) carried one or more β-lactamase genes, with bla[sub.OXA-488] (19%) and bla[sub.VEB-9] (45.2%) being predominant. A strong association was detected between class B β-lactamase genes and both ceftazidime–avibactam and ceftolozane–tazobactam resistance, while class A genes were associated with ceftolozane–tazobactam resistance. Co-resistance to ceftazidime–avibactam and ceftolozane–tazobactam correlated with the presence of bla[sub.VEB-9], bla[sub.PDC-35], bla[sub.VIM-2], bla[sub.OXA-10] and bla[sub.OXA-488]. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B β-lactamases (bla[sub.VIM-2]) and class D β-lactamases (bla[sub.OXA-10]), while ceftolozane–tazobactam resistance was associated with class A (bla[sub.VEB-9]), class C (bla[sub.VPDC-35]), and class D β-lactamases (bla[sub.OXA-488]).