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)

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.

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.

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.

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).