Understanding how biological sex and gender disparities contribute to suboptimal treatment of sepsis

Sepsis is still the leading cause of mortality in ICUs worldwide. Despite advances in early detection and treatment, standardized antibiotic dosing often ignores patient-level variation—especially that associated with sex-related physiology and gender-influenced care disparities.

A recently published article in Journal of Intensive Medicine on September 8, 2025, calls attention to how biological sex and gender disparities contribute to suboptimal sepsis treatment, potentially compromising outcomes for women. Author of Dr. Helena Barrasa, by Dr. Goiatz Balziskueta and Professor Jordi Rello, the article highlights the overlooked pharmacokinetic and pharmacodynamic differences between men and women and urges the integration of sex and gender into antimicrobial dosing protocols.

The article highlights that women often face both underrepresentation in pharmacologic trials and higher risks of overexposure to antibiotics. Hormonal fluctuations, body composition, and renal clearance affect how drugs are processed, yet these variables are rarely considered in dosing algorithms. Meanwhile, men—particularly younger individuals with increased renal clearance—may be underdosed, leading to treatment failure.

“Standard dosing overlooks key biological differences” the authors said. “Women, because of their altered metabolism and lower muscle mass, are more vulnerable to side effects, while young men often come off 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 early interventions, with differences stemming from misinterpretation of symptoms, health care-seeking behaviors, or indirect bias in emergency systems.

These disparities compound the biological differences that already affect pharmacokinetics and pharmacodynamics. Standardized dosing often overlooks how women are more susceptible to antibiotic overexposure and adverse effects, while younger men with increased renal clearance experience underdosing and treatment failure. Such imbalances highlight the urgency of finer tailoring of antimicrobial therapy.

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

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