To Örebro University

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^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_OXA-488 (19%) and bla_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_VEB-9, bla_PDC-35, bla_VIM-2, bla_OXA-10 and bla_OXA-488. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B β-lactamases (bla_VIM-2) and class D β-lactamases (bla_OXA-10), while ceftolozane-tazobactam resistance was associated with class A (bla_VEB-9), class C (bla_VPDC-35), and class D β-lactamases (bla_OXA-488).