INVICTUS II: comparison of disc diffusion and broth microdilution methods for susceptibility testing of ceftolozane/tazobactam and five comparator agents against a subset of INVICTUS I Pseudomonas aeruginosa clinical isolates.

OBJECTIVES

A subset of clinical Pseudomonas aeruginosa isolates from the INVICTUS I study was selected to compare antimicrobial susceptibility performance for disc diffusion and broth microdilution of ceftolozane/tazobactam and five comparator antipseudomonal agents.

METHODS

Overall, 159 non-cystic fibrosis isolates were chosen from INVICTUS I that had the smallest zone diameters from disc testing to ceftolozane/tazobactam, including isolates that were close to the breakpoints. The isolates were tested across 14 centres in the UK. Susceptibility results were interpreted using EUCAST 2026 criteria.

RESULTS

Discrepancy analysis showed combined error rates (very major and major errors) highest for ceftolozane/tazobactam, ceftazidime and piperacillin/tazobactam (15.7%, 14.5% and 12.6%, respectively); when adjusted to remove isolates close to the breakpoint for ceftolozane/tazobactam and piperacillin/tazobactam there were still remarkably high error rates (10.6% and 7.2%, respectively). Essential agreement and bias analysis were not performed as MICs were being compared with zone diameters.

DISCUSSION: Our findings highlight substantial challenges in performing and interpreting susceptibility testing for these two important antipseudomonal β-lactam/β-lactamase inhibitors, which are commonly employed as either first-line empirical therapy (piperacillin/tazobactam) or for serious and MDR infection (ceftolozane/tazobactam). A review of disc testing for these agents may be warranted, and diagnostic laboratories may wish to review the technical limitations and put in place mitigating measures.