SEX-linked biology and care patterns may shape bloodstream infections from diagnosis through antibiotic exposure and survival.
Sex Differences in Bloodstream Infections
Bloodstream infections remain a major global cause of mortality, with management complicated by antimicrobial resistance, comorbidities, immunosuppression, and deep-seated infections involving medical hardware. A new review highlights sex as an underreported factor that may influence the epidemiology, management, and outcomes of bloodstream infections.
Current evidence suggests that bloodstream infection incidence is generally higher in males. One large U.S. cohort reported higher incidence in males than females, at 237 versus 156 per 100,000 person-years, with the gap more pronounced in older males. Similar findings from Norway and Swiss surveillance data showed higher overall bloodstream infection incidence in males, although Escherichia coli bloodstream infections occurred more often in females. Increased risk of Staphylococcus aureus bloodstream infection appears to be a major driver of higher male incidence.
Biology, Prescribing, And Diagnosis
Sex-related immune differences may influence how bloodstream infections develop and progress. Females tend to show lower susceptibility to severe bacterial infections and faster pathogen clearance, potentially reflecting estrogen-associated immune-enhancing effects and the immunosuppressive properties of testosterone. However, the review emphasizes that immune differences are complex and also involve genetics, immune cell function, and host pathogen interactions.
Sex-related differences also extend into antimicrobial therapy. Females are more likely to receive antibiotics, and these prescriptions are more often inappropriate, including for viral infections. In severe infections, several studies have reported longer time to antibiotic administration in females presenting with sepsis, as well as lower adherence to sepsis bundle protocols.
Diagnostic gaps may also affect care. In S. aureus bloodstream infection, female patients were less likely to undergo echocardiography and received shorter antibiotic courses. In a European intensive care cohort of patients with pneumonia, females were less likely than males to undergo bronchoscopy.
Toward Individualized Infection Care
Pharmacokinetic and pharmacodynamic differences may further affect bloodstream infections treatment. Sex can influence absorption, distribution, metabolism, and excretion, while adverse drug reactions occur more often in females across several drug classes, including antibiotics. Reported examples include higher hypokalemia risk with high-dose flucloxacillin and greater QT prolongation with moxifloxacin.
Outcomes vary by pathogen. Mortality appears higher in females with S. aureus bacteremia, while gram-negative bloodstream infection mortality differences may be explained partly by infection source. These findings point to a complex interaction between sex, pathogen, source, diagnostic intensity, and therapeutic decisions.
The review concludes that sex and gender affect nearly every aspect of bloodstream infections, yet sex-disaggregated data remain inconsistently reported. More sex-responsive study designs, better reporting, and greater awareness could support more individualized treatment strategies for all patients with bloodstream infections.
Reference
Westgeest AC et al. The impact of sex on therapy, epidemiology, and outcome for bloodstream infections. Expert Review of Anti-Infective Therapy. 2026;doi:10.1080/14787210.2026.2692486.
Featured Image: NanSan on Adobe Stock.
- Author:
