In vitro activity of ceftolozane/tazobactam against Gram-negative isolates collected from ICU patients with lower respiratory tract infections in seven Asian countries-SMART 2017-2019

Objectives: Antimicrobial resistance is one of the top 10 global public-health threats. Especially high rates of resistance have been reported for isolates from ICU patients, requiring expanded treatment options in this setting. We evaluated the activity of ceftolozane/tazobactam and comparators against Gram-negative isolates collected from patients with lower respiratory tract infections (LRTIs) in ICUs in seven Asian countries.

Methods: In 2017-2019, up to 100 consecutive, aerobic Gram-negative LRTI isolates were collected per year at each of 37 hospitals. MICs were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method.

Results: Overall, ceftolozane/tazobactam was active against 72% of 1408 Enterobacterales and 86% of 761 Pseudomonas aeruginosa isolates. Susceptibility to the non-carbapenem β-lactam comparators, including piperacillin/tazobactam, was 52-67% among Enterobacterales isolates, and the activity of all β-lactam comparators, including meropenem, was 57-70% among P. aeruginosa. Ceftolozane/tazobactam maintained activity against 61% of meropenem-nonsusceptible and 64% of piperacillin/tazobactam-nonsusceptible P. aeruginosa. At the country-level, ceftolozane/tazobactam activity ranged from >90% against Enterobacterales from Hong Kong and South Korea to <64% in Thailand and Vietnam, and from >90% against P. aeruginosa from South Korea, Malaysia, Philippines and Taiwan to <75% in Thailand and Vietnam. Correspondingly, the proportions of carbapenemase-positive isolates among Enterobacterales and P. aeruginosa isolates were highest in Thailand and Vietnam.

Conclusion: Ceftolozane/tazobactam provides a potential treatment option for ICU patients in Asia, which is especially important considering the reduced activity of commonly used β-lactams against the studied ICU isolates. Knowledge of local resistance patterns should inform empirical therapy decision-making.