1581 - In Vitro Activity of Ceftolozane/Tazobactam against Pseudomonas aeruginosa from ICU and Non-ICU Patients with Respiratory Tract Infections in the Asia/Pacific region – SMART 2016-2018

Background: Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Elevated antimicrobial resistance rates have been reported among pathogens collected in ICUs. Using isolates collected in Asia/Pacific as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against P. aeruginosa from patients with respiratory tract infections (RTI) in ICU and non-ICU wards.

Methods: In 2016-2018, 55 clinical laboratories in 11 Asia/Pacific countries collected 2530 P. aeruginosa isolates from RTI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints. C/T-nonsusceptible isolates (except those from India) were screened by PCR and sequencing for genes encoding β-lactamases.

Results: Susceptibility to C/T in Asia/Pacific was 85.3% in ICUs and 92.2% in non-ICUs, 15-23 percentage points and 13-19 percentage points, respectively, higher than to meropenem, cefepime, and piperacillin-tazobactam. C/T maintained activity against 58.8% and 69.4% of meropenem-nonsusceptible isolates from ICU (n=294) and non-ICU patients (n=346), respectively. Acquired β-lactamases were detected in 64% of C/T-nonsusceptible isolates from ICUs (n=90; 54% MBL-positive, 1% GES carbapenemase-positive, 9% ESBL-positive) and in 47% of C/T-NS isolates from non-ICUs (n=86; 33% MBL-positive, 6% GES-carbapenemase-positive, 8% ESBL-positive). The table presents country-level rates of C/T-susceptible and carbapenemase-positive P. aeruginosa for countries with n >20 in both ICU and non-ICU subsets.Table


Conclusion: In Asia/Pacific overall, C/T maintained susceptibility rates >85% in both ICU and non-ICU wards against P. aeruginosa isolates from RTI, with rates >91% in most countries. Susceptibility was lower in countries with higher rates of carbapenemase-positive P. aeruginosa. C/T could provide an important treatment option for RTI infections caused by P. aeruginosa in the Asia/Pacific region.