Understanding how biological sex and gender inequities contribute to suboptimal sepsis treatment

Sepsis continues to be a leading cause of mortality in ICUs worldwide. Despite advances in early detection and treatment, standardized antibiotic dosing frequently ignores patient-level variability-especially that associated with sex-related physiology and gender-influenced care disparities.

A newly published editorial in the Journal of Intensive Medicine on September 8, 2025, is calling attention to how biological sex and gender inequities contribute to suboptimal sepsis treatment, potentially compromising outcomes for women. Authored by Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello, the piece highlights overlooked pharmacokinetic and pharmacodynamic differences between men and women, and urges the integration of sex and gender into antimicrobial dosing protocols.

The editorial emphasizes that women often face both underrepresentation in pharmacological trials and higher risks of antibiotic overexposure. Hormonal fluctuations, body composition, and renal clearance all influence how drugs are processed, yet these variables are rarely considered in dosing algorithms. Meanwhile, men-especially younger individuals with augmented renal clearance-may be underdosed, leading to treatment failure.

"Standard dosing overlooks key biological differences," said the authors. "Women, due to altered metabolism and lower muscle mass, are more vulnerable to adverse effects, while young men often eliminate drugs too quickly to maintain therapeutic levels."

Beyond biology, gender roles and biases further complicate sepsis care. Women are less likely than men to receive aggressive or timely interventions, with disparities stemming from symptom misinterpretation, healthcare-seeking behaviors, or implicit bias within emergency systems.

These inequities compound the biological differences already influencing pharmacokinetics and pharmacodynamics. Standardized dosing often overlooks how women are more prone to antibiotic overexposure and adverse reactions, while younger men with augmented renal clearance face underdosing and treatment failure. Such imbalances highlight the urgency of tailoring antimicrobial therapy more precisely.

The authors advocate for wider use of therapeutic drug monitoring to individualize treatment and reduce both toxicity and resistance. They also call on the scientific community to integrate sex- and gender-aware research protocols, noting that fewer than 30% of studies currently report sex-stratified data.

In conclusion, Prof. Rello stated, "Understanding the differences shaped by sex and gender is essential to advancing personalized medicine and represents a commitment to reducing the equity gap."