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 (LRTI) 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 P. 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 isolates. At the country-level, ceftolozane/tazobactam activity ranged from >90% against Enterobacterales isolates 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.

CONCLUSIONS: 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 empiric therapy decision-making.