Ceftolozane/Tazobactam Activity Against Drug-Resistant Pseudomonas aeruginosa and Enterobacterales Causing Healthcare-Associated Infections in Eight Asian Countries: Report from an Antimicrobial Surveillance Program (2016–2018)

Abstract

Purpose: To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Pseudomonas aeruginosa and Enterobacterales isolates from hospitalised patients in Asia. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. Methods: A total of 2038 Gram-negative organisms (376 P. aeruginosa and 1662 Enterobacterales) were collected consecutively using a prevalence-based approach from 11 medical centres. Organisms were susceptibility tested by broth microdilution according to CLSI guidelines. CLSI and EUCAST breakpoint criteria were used. Results: Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/4 mg/L) β-lactam agent tested against P. aeruginosa isolates, inhibiting 91.0% of the isolates at an MIC of ≤4 mg/L. P. aeruginosa exhibited high rates of susceptibility to amikacin (92.0/92.0% [CLSI/EUCAST]) and colistin by EUCAST criteria only (99.2% intermediate [CLSI]/99.2% susceptible [EUCAST]). Ceftolozane/ tazobactam (MIC50/90, 0.25/16 mg/L; 86.8/86.8% susceptible [CLSI/EUCAST]) and meropenem (MIC50/90, 0.03/0.12 mg/L; 93.0/ 93.3% susceptible [CLSI/EUCAST]) were the most active compounds tested against Enterobacterales. Isolates displayed susceptibility rates to other β-lactam agents, ranging from 81.5/77.7% for piperacillin/tazobactam, 66.0/64.5% for cefepime, and 65.3/60.9% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacterales isolates, 6.8% were carbapenem-resistant Enterobacterales (CRE) and 29.6% exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. Ceftolozane/tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacterales (MIC50/90, 0.5/8 mg/L; 84.8/84.8% susceptible), but not against isolates with a CRE phenotype (MIC50/90, >32/>32 mg/L). Conclusion: Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than the available cephalosporins when tested against Enterobacterales from Asian countries.