Female Sex and Mortality in Patients With Gram-Negative Bacteremia: A Systematic Review and Meta-Analysis.

Importance: Female sex has been identified as a risk factor for mortality in Staphylococcus aureus bloodstream infection (SA-BSI). It is unknown whether this association extends to bloodstream infections with other bacterial species. Objective: To investigate whether female sex is associated with increased mortality risk among patients with gram-negative bloodstream infection (GN-BSI). Data Sources: MEDLINE, Embase, and Web of Science were searched from inception to January 8, 2025. Study Selection: Study inclusion criteria were randomized or observational studies assessing adults with GN-BSI that included at least 100 patients and reported mortality at or before 90 days following GN-BSI, with mortality stratified by sex and, when applicable, by gram-negative bacterial species. Studies with polymicrobial GN-BSI were excluded. For inclusion in the primary analysis, studies must have stratified or statistically adjusted for confounding variables between female and male patients with GN-BSI. A secondary analysis included studies that reported sex-stratified unadjusted mortality. Data Extraction and Synthesis: One reviewer conducted extraction and quality assessment, which was verified by a second reviewer. Risk of bias and quality were assessed with the Newcastle-Ottawa Quality Assessment Scale. Mortality data were combined as odds ratios (ORs). The study followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Main Outcome and Measures: Mortality at or before 90 days following GN-BSI, stratified by sex. Results: From 9752 studies retrieved, 25 (16 350 patients; 4017 female [25%], 12 333 male [75%]) were included in the primary analysis. Female patients with GN-BSI did not have increased risk of mortality relative to male patients (pooled OR, 0.98 [95% CI, 0.81-1.17]). No publication bias was identified. Subset analyses based on medical comorbidities, timing of mortality end point, bacterial species group, antibiotic resistance phenotype, and publication date did not reveal a set of patients with differences in sex-stratified mortality. A total of 321 studies (147 810 patients) that reported unadjusted mortality were included in a secondary analysis. In this analysis, female sex was associated with decreased risk of mortality (pooled OR, 0.90 [95% CI, 0.86-0.94]). Conclusions and Relevance: In this systematic review and meta-analysis, female patients with GN-BSI were not at higher risk than male patients of mortality after statistical adjustment. GN-BSI and SA-BSI thus differ in sex-specific mortality outcomes, highlighting the need for further research into the immunological, pathophysiological, and clinical management factors that may be associated with sex disparities in SA-BSI but not in GN-BSI.