Ceftolozane/tazobactam and imipenem/relebactam cross-susceptibility among clinical isolates of Pseudomonas aeruginosa from patients with respiratory tract infections in ICU and non-ICU wards – SMART United States 2017-2019

Abstract

Abstract Background Carbapenem-nonsusceptible and multidrug-resistant (MDR) P. aeruginosa, which are more common in patients with lower respiratory tract infections (LRTIs) and in patients in ICUs, pose difficult treatment challenges and may require new therapeutic options. Two β-lactam/β-lactamase-inhibitor combinations, ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL), are approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia. Methods CLSI-defined broth microdilution methodology was used to determine MICs against P. aeruginosa isolates collected from patients with LRTIs in ICU (n=720) and non-ICU wards (n=914) at 26 United States hospitals in 2017-2019 as part of the SMART surveillance program. Results Susceptibility to commonly used β-lactams including carbapenems was 5-9 percentage points lower and MDR rates 7 percentage points higher among isolates from patients in ICUs than non-ICU wards (p<0.05). C/T and IMI/REL maintained activity against 94.0% and 90.8% of ICU isolates, respectively, while susceptibility to all comparators except amikacin (96.0%) was 63-76%. C/T and IMI/REL inhibited 83.1% and 68.1% of meropenem-nonsusceptible (n=207) and 71.4% and 65.7% of MDR ICU isolates (n=140), respectively. Among all ICU isolates, only 2.5% were nonsusceptible to both C/T and IMI/REL, while 6.7% were susceptible to C/T but not to IMI/REL, and 3.5% were susceptible to IMI/REL but not to C/T. Conclusions These data suggest that susceptibility to both C/T and IMI/REL should be considered for testing at hospitals, as both agents could provide important new options for treating patients with LRTIs, especially in ICUs where collected isolates showed substantially reduced susceptibilities to commonly used β-lactams.