Mortality in infections caused by metallo-β-lactamase- versus serine carbapenemase-producing Enterobacterales: a...

Whether carbapenemase class independently influences prognosis in carbapenemase-producing Enterobacterales (CPE) infections remains uncertain.

We aimed to evaluate whether infections caused by metallo-β-lactamase (MBL)- vs. serine β-lactamase (SBL)-producing Enterobacterales are associated with differences in mortality among hospitalized adults.

This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidance.

MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to 28 February 2026.

Observational studies reporting all-cause mortality stratified by carbapenemase class, type, or carbapenemase-defined group were included.

Hospitalized adults aged ≥16 years with CPE infection.

Infection caused by MBL-producing vs. SBL-producing Enterobacterales.

Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Exposures (ROBINS-E), and Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Adjusted hazard ratios (aHRs) were pooled when available, adjusted ORs (aORs) were summarized descriptively, and crude mortality was pooled as ORs using random-effects models oriented as MBL vs. SBL.

Seventeen observational studies were included (n = 2429). Three studies contributed aHRs; exploratory synthesis suggested a difference in mortality between MBL- and SBL-producing infections (aHR 0.67, 95% CI 0.48-0.92; I² = 5.6%), but this finding was limited by residual confounding, heterogeneous adjustment models, and derivation/inversion of some estimates. aORs were summarized descriptively because mortality timepoints, comparators, and adjustment methods differed. Crude mortality did not clearly differ overall between MBL- and SBL-producing infections (OR 0.77, 95% CI 0.57-1.03; I² = 29.6%). Treatment reporting was heterogeneous, particularly regarding timing of active therapy and MBL-active agents.

Mortality comparisons between infections caused by MBL-producing and SBL-producing Enterobacterales did not show a clear difference, but certainty of evidence was very low. Carbapenemase class alone is unlikely to determine prognosis; host characteristics, infection severity, circulating clones, access to active antimicrobial agents, and timely initiation of appropriate therapy are likely to influence outcomes.