Clinical outcomes of carbapenem therapy in OXA-48-producing Enterobacterales infections: a French multicentre cohort, systematic review, and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not specified but CI excludes null

• Effect Size: OR = 2.02 for increased clinical failure with carbapenems

• Primary Outcome: Clinical failure with carbapenem therapy vs alternative active regimens

• Nnt Or Sensitivity: NNH approximately 4-5 patients (based on 30.7% vs 52% mortality rates)

• Confidence Interval: 95% CI = 1.05-3.88

Clinical Application

Alternative agents like ceftazidime-avibactam available in Australian tertiary centres but PBS restrictions may limit access Highly relevant given increasing carbapenem resistance in Australia; supports TGA-approved alternatives and aligns with AURA surveillance priorities Patients with confirmed OXA-48-producing Enterobacterales infections in hospital settings

Abstract

OXA-48-producing Enterobacterales (OXA-48-PE) represent a growing global health threat. Most of OXA-48-PE remain categorized susceptible to carbapenems, which might encourage their use despite uncertain clinical efficacy. This study evaluated clinical outcomes of infections caused by OXA-48-PE treated with carbapenem compared with alternative active therapies. The analyses were performed at three levels: a descriptive analysis of the French cohort, a comparative descriptive analysis of all published studies, and a meta-analysis restricted to studies providing direct comparisons between carbapenem-based and alternative active regimens. Between September 2021 and March 2023, 59 patients with monomicrobial OXA-48-PE infections were included in a French multicenter retrospective cohort. In parallel, a systematic review was conducted to identify clinical studies published through 31 December 2024, reporting outcomes of OXA-48-PE infections. In the French cohort, the overall 30-day mortality was 49.1%. Clinical failure occurred in 57.1% of patients receiving meropenem monotherapy, including patients infected with isolates exhibiting meropenem MICs within the susceptible range. Across 12 clinical studies (817 patients), carbapenem therapy was associated with high and variable crude mortality (52%), whereas newer agents active against OXA-48-PE, particularly ceftazidime-avibactam, were associated with lower and more consistent crude mortality (30.7%). In the primary meta-analysis of 6 human comparative studies, carbapenem therapy was associated with an increased risk of clinical failure compared with alternative active regimens (OR = 2.02; 95% CI = 1.05-3.88). Despite apparent in vitro susceptibility, carbapenem therapy was consistently associated with unfavourable clinical outcomes in OXA-48-PE infections, supporting the prioritization of alternative active agents whenever available.

References

1. 1.Dortet, L., Moreau, C., Dinh, A., Bonnin, R. A., Escaut, L., Seguret, M., Weber, L., Figueiredo, S., & Pilmis, B. (2026). Clinical outcomes of carbapenem therapy in OXA-48-producing Enterobacterales infections: a French multicentre cohort, systematic review, and meta-analysis. Emerging Microbes & Infections. https://doi.org/10.1080/22221751.2026.2671518