225 Meta-analysis female sex and mortality in SAB 10 outcome as well. Delays in antibiotic treatment and less invasive treatment have been reported in women with septic shock and critical illness [105,117-119], and women were less likely to receive the recommended quality of acute care compared with men in a US study on quality of care in sociodemographic subgroups [120]. In a 2023 cohort study from our research group [121], women with SAB received shorter durations of antimicrobial treatment and were less likely to undergo transesophageal echocardiography compared to men. Regional or cultural differences in health care delivery could be impacting the observed sex-based difference in patient outcomes. The association between female sex and mortality varied to some degree by location of study, and we have previously shown that there is considerable global variation in SAB treatment factors [102]. Finally, response to treatment can differ between female and male patients. Both pharmacokinetics and pharmacodynamics are generally subject to sex influences [122]. Limitations This study had several limitations. First, sex difference was not the primary outcome of interest in the majority of the included studies. Therefore, a number of studies did not include adjusted data for mortality by sex, and inclusion of this data could have influenced the results. Second, reporting bias can exist as studies may not report mortality stratified by sex if there was no significant difference in mortality. Third, heterogeneity exists not only in study methodology but also in the disease itself. The clinical presentation of SAB may vary from uncomplicated intravenous catheterrelated bacteremia to complicated metastatic disease. Because all studies on SAB patients were included in our study, sex-based differences in outcome could not be stratified by infection severity. Lastly, whether reported sex represented sex assigned at birth or gender, was often not specified. Conclusions In this systematic review and meta-analysis, observational cohort studies demonstrated an association between female sex and increased mortality risk in adult patients with SAB. This association remained significant after including only studies that adjusted for patient clinical and treatment variables. Future research should focus on understanding the underlying causes and on promoting better outcomes in female patients with SAB. Fundamental research on biological sex differences in immune response or pharmacology, examinations of sex-based differences in management of SAB, and better reporting of sex-specific outcomes in randomized clinical trials are necessary to better understand the observed sex-specific differences in mortality among patients with SAB.
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