Infectious diseases and therapy · 2026
Clinical-Microbiological Discordance and Delayed Mortality in OXA-48/ESBL-Producing Proteus mirabilis Infections.
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Machuca Isabel, Pineda Juan J, Marín-Sanz Juan A, Riazzo Cristina, Guzmán-Puche Julia, Cano Ángela, Moya-Riballo Raquel, De la Torre-Capitán Noelia, Bermúdez Carmen, Rodríguez Jorge, Castón Juan J, Pérez-Nadales Elena, Kieffer Nicolas, Gracia-Ahufinger Irene, Ruiz-Arabi Elisa, Carmona Isabel, Pozo Lorena, Cosano Patricia, Baumela Andrés, de la Fuente Carmen, Martínez-Martínez Luis, Torre-Cisneros Julián
Аннотация
INTRODUCTION: OXA-48/extended-spectrum β-lactamase (ESBL)-producing Proteus mirabilis may appear susceptible to carbapenems in routine testing, potentially resulting in inappropriate therapeutic decisions. We aimed to evaluate clinical outcomes and the association between antimicrobial therapy and mortality.
METHODS: We conducted a single-center observational study including 1254 patients with P. mirabilis infections (2017-2024). Seventy-nine OXA-48/ESBL cases (6.3%) were matched 2:1 with non-OXA-48/ESBL controls based on age, comorbidity, infection source, and severity. OXA-48 production was detected using the NG-Test CARBA 5 immunochromatographic assay, while ESBL production was inferred phenotypically using cefotaxime, ceftazidime, and cefepime discs alone and in combination with clavulanic acid. Predictors of 30-day mortality were assessed using time-dependent Cox regression models.
RESULTS: OXA-48/ESBL-producing infections were associated with higher 30-day mortality (absolute difference 19.7%; population attributable fraction 18.2%). Differences in mortality emerged after day 8, suggesting delayed clinical deterioration. In time-dependent models, OXA-48/ESBL status was not associated with early mortality (days 0-7) but strongly predicted late mortality [hazard ratio (HR) 14.5; 95% confidence interval (CI) 3.19-65.93; p = 0.001]. Among patients with OXA-48/ESBL infections, carbapenem-based regimens were associated with higher mortality than alternative active therapies (50% vs. 20%; p = 0.04), remaining significant after adjustment (HR 3.37; 95% CI 1.27-8.9), although residual confounding by indication cannot be excluded.
CONCLUSION: These observational findings support cautious interpretation of carbapenem susceptibility results and highlight the value of early carbapenemase detection to guide appropriate therapy. Graphical abstract available for this article.
METHODS: We conducted a single-center observational study including 1254 patients with P. mirabilis infections (2017-2024). Seventy-nine OXA-48/ESBL cases (6.3%) were matched 2:1 with non-OXA-48/ESBL controls based on age, comorbidity, infection source, and severity. OXA-48 production was detected using the NG-Test CARBA 5 immunochromatographic assay, while ESBL production was inferred phenotypically using cefotaxime, ceftazidime, and cefepime discs alone and in combination with clavulanic acid. Predictors of 30-day mortality were assessed using time-dependent Cox regression models.
RESULTS: OXA-48/ESBL-producing infections were associated with higher 30-day mortality (absolute difference 19.7%; population attributable fraction 18.2%). Differences in mortality emerged after day 8, suggesting delayed clinical deterioration. In time-dependent models, OXA-48/ESBL status was not associated with early mortality (days 0-7) but strongly predicted late mortality [hazard ratio (HR) 14.5; 95% confidence interval (CI) 3.19-65.93; p = 0.001]. Among patients with OXA-48/ESBL infections, carbapenem-based regimens were associated with higher mortality than alternative active therapies (50% vs. 20%; p = 0.04), remaining significant after adjustment (HR 3.37; 95% CI 1.27-8.9), although residual confounding by indication cannot be excluded.
CONCLUSION: These observational findings support cautious interpretation of carbapenem susceptibility results and highlight the value of early carbapenemase detection to guide appropriate therapy. Graphical abstract available for this article.