Insertion of ISPa1635 in ISCR1 Creates a Hybrid Promoter for bla(PER-1) Resulting in Resistance to Novel β-lactam/β-lactamase Inhibitor Combinations and Cefiderocol

Eleven bla(PER-1)-positive Pseudomonas aeruginosa clinical isolates showed variable susceptibility to ceftazidime-avibactam (CZA). The genetic contexts of bla(PER-1) were identical (ISCR1-bla(PER-1)-gst) except for the ST697 isolate HS204 (ISCR1-ISPa1635-bla(PER-1)-gst). The insertion of ISPa1635 in ISCR1 upstream of bla(PER-1) created a hybrid promoter, which elevated the bla(PER-1) transcription level and resulted in increased resistance to CZA, ceftolozane-tazobactam, cefepime-zidebactam, and cefiderocol. Diversity in the promoter activity of bla(PER-1) partially explains the variable susceptibility to CZA in PER-producing isolates.