ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2026
Initial empiric carbapenem versus non-carbapenem β-lactam/β-lactamase inhibitor therapy in sepsis across simplified SENECA phenotypes: a retrospective study of two independent cohorts.
Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeWhether initial empiric carbapenem therapy is associated with better outcomes than non-carbapenem β-lactam/β-lactamase inhibitor (BL/BLI) therapy in sepsis remains uncertain. We examined this association overall and across simplified Sepsis Endotyping in Emergency Care (SENECA) phenotypes.
methodsThis retrospective study included 4,091 patients from MIMIC-IV and 405 patients from a single-center hospital cohort. Initial therapy was defined by the first eligible carbapenem or BL/BLI regimen initiated within 24 h of admission. The primary outcome was 28-day mortality. Secondary outcomes included selected clinical and in-hospital microbiological detection outcomes. Each cohort was analyzed separately using inverse probability of treatment weighting and weighted logistic regression.
resultsAfter weighting, no overall association with lower 28-day mortality was observed in MIMIC-IV (OR 0.91, 95% CI 0.71-1.17) or the hospital cohort (OR 0.74, 95% CI 0.48-1.16). However, evidence of treatment-by-phenotype interaction was observed in both cohorts (P for interaction = 0.039 and 0.019, respectively), with lower odds of 28-day mortality among patients with the γ phenotype in MIMIC-IV and the hospital cohort (OR 0.66, 95% CI 0.44-0.97, and OR 0.13, 95% CI 0.04-0.46, respectively). A similar direction was observed among mechanically ventilated patients. In MIMIC-IV, carbapenem therapy was associated with longer hospitalization and more frequent detection of fungal organisms and Clostridioides difficile; these associations were not observed in the hospital cohort.
conclusionInitial empiric carbapenem therapy was not significantly associated with lower 28-day mortality overall. Consistent findings in the γ phenotype suggest possible treatment heterogeneity. These findings should be considered alongside patient characteristics and potential clinical and microbiological trade-offs.
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