Are Women at Greater Risk? Rethinking Sepsis Antibiotic Dosing

The editorial highlights how sex and gender differences affect antibiotic dosing, treatment response, and sepsis outcomes.

Sepsis remains one of the leading causes of death in intensive care units (ICUs) around the world. While advances in early detection, supportive care, and treatment strategies have improved outcomes, standardized antibiotic dosing protocols often fail to account for individual patient variability ().

In particular, differences in biological sex and the influence of gender on healthcare delivery are frequently overlooked, potentially leading to suboptimal treatment outcomes.

Neutropenic Sepsis
Neutropenic sepsis is a potentially life-threatening condition when a patient with low neutrophil counts develops an infection that spirals out of control if not treated urgently and is usually seen in cancer patients on chemotherapy.

TOP INSIGHT

The "one-size-fits-all" approach in #sepsis is failing. Women are at higher risk of #drugtoxicity due to lower #musclemass and slower drug clearance. Young men with high clearance are often underdosed, risking treatment failure. Time for Therapeutic Drug Monitoring (#TDM) to close this gap.

A recent editorial published in the Journal of Intensive Medicine emphasizes the critical need to consider sex and gender in sepsis management.

Sex and Gender Differences in Antibiotic Dosing

Authored by Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello, the piece draws attention to the pharmacokinetic and pharmacodynamic differences between men and women that can significantly influence how antibiotics are metabolized and utilized.

The authors argue that ignoring these differences—and the broader gender-related disparities in healthcare access and treatment—can compromise patient outcomes, particularly for women, and call for the integration of sex- and gender-informed approaches into antimicrobial dosing strategies.

Septicemia
Septicemia or sepsis is a serious illness wherein a patient develops symptoms due to presence of microbes or their toxins in the blood. Septicemia or sepsis is caused by bacteria, viruses and fungi.

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."

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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.

Addressing Sex and Gender Gaps in Sepsis Care

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.

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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."

Reference:

Sex-related differences in antimicrobial dosing for sepsis: Bridging the equity gap - (https://www.sciencedirect.com/science/article/pii/S2667100X2500057X?via%3Dihub)

Source-Eurekalert