Redefining susceptibility in practice : clinical and resistance outcomes of the EUCAST 'I' category for wild-type Pseudomonas aeruginosa.

BACKGROUND

The 2019 EUCAST redefinition of the "susceptible, increased exposure" (I) category aimed to optimize antimicrobial therapy and reduce unnecessary carbapenem prescribing. However, concerns remain that misinterpretation may promote carbapenem overuse. We evaluated clinical and resistance outcomes associated with I-category agents compared to meropenem in wild-type (WT) Pseudomonas aeruginosa infections.

METHODS

In this retrospective cohort study, adult inpatients with microbiologically confirmed WT P. aeruginosa infections between January 2020 and March 2024 were included. Eligible isolates were susceptible to meropenem and categorized as "I" to at least one antipseudomonal agent (piperacillin-tazobactam, ceftazidime, cefepime, or ciprofloxacin). Patients received either I-category agents or meropenem as definitive therapy. Primary outcomes were clinical failure and all-cause mortality. Secondary outcomes included emergence of carbapenem-resistant microorganisms within one year.

RESULTS

A total of 411 patients were included (I group n = 152; meropenem group n = 259). Clinical failure (9.2% vs. 6.9%, p = 0.409) and mortality at all time points were comparable between groups. However, meropenem use was independently associated with the development of carbapenem-resistant P. aeruginosa (CRPA) within one year (OR 2.38, 95% CI 1.02-5.57; p = 0.046). In contrast, emergence of any carbapenem-resistant organism was associated with prior antibiotic exposure and disease severity, but not treatment group.

CONCLUSION

In WT P. aeruginosa infections, treatment with EUCAST I-category agents achieved clinical outcomes comparable to meropenem. However, meropenem use was independently associated with subsequent CRPA isolation. These findings support carbapenem-sparing strategies and highlight the long-term resistance implications of antimicrobial selection following the EUCAST redefinition.