One-size-fits-all dosing has always harmed some patients more than others.
In intensive care units around the world, a quiet inequity persists at the intersection of biology and institutional habit: sepsis patients receive antibiotic doses calibrated to a generalized body that does not exist. A new editorial by Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello argues that biological sex and gender bias together distort treatment outcomes — leaving women vulnerable to toxicity and men to underdosing. The science of precision medicine has long offered a path forward, yet the will to walk it has lagged behind the knowledge that demands it.
- Sepsis remains one of the leading killers in intensive care, and its standard antibiotic dosing protocol treats every patient as physiologically interchangeable — a fiction that costs lives.
- Women metabolize antibiotics more slowly and accumulate dangerous drug levels, while young men clear them so rapidly that infections persist unchecked — two opposite failures born from the same indifference to difference.
- Gender bias in emergency settings compounds the pharmacological problem: women receive less aggressive care, face slower responses, and enter treatment already at a systemic disadvantage.
- Fewer than 30 percent of clinical studies report sex-disaggregated data, meaning the dosing guidelines harming women were built on evidence that barely included them.
- Therapeutic drug monitoring — measuring real antibiotic levels in real patients in real time — already exists and works, but requires institutional commitment that has not yet materialized at scale.
- Researchers and hospitals now face a clear choice: continue optimizing for an average patient who represents no one, or build dosing protocols on evidence that finally accounts for who is actually in the bed.
Sepsis is among the most lethal conditions treated in intensive care, and while early detection has improved, something foundational remains unaddressed: antibiotic dosing is still calibrated as though all patients share the same body.
An editorial published in the Journal of Intensive Medicine by Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello argues that biological sex and gender inequity are quietly eroding sepsis outcomes worldwide. The mechanism is straightforward but consequential. Women carry less muscle mass, metabolize drugs differently, and clear certain medications at slower rates than men. When a standard dose is administered, women tend to accumulate excess antibiotic, raising the risk of toxicity. Young men face the opposite problem — their rapid drug clearance means therapeutic levels never stabilize, and infections persist. The same protocol, two different failures.
The harm does not stop at pharmacokinetics. Gender shapes how patients are received in emergency settings. Women are less likely to receive timely or aggressive interventions, and unconscious bias among care providers can slow the response to their deteriorating condition. These institutional patterns layer onto biological ones, deepening the disparity before treatment has even begun.
The authors also identify a structural flaw in the evidence itself: fewer than 30 percent of relevant studies report results broken down by sex. Dosing guidelines for half the population have been built on data that barely represents them.
The editorial calls for two correctives. Therapeutic drug monitoring — adjusting doses based on measured antibiotic levels in each patient's blood — is already available and effective, requiring only commitment to deploy. Equally important, future research must treat sex-stratified data as standard practice rather than an afterthought. Prof. Rello framed the stakes plainly: precision medicine and equity are not separate goals here. One-size-fits-all dosing has always been a compromise, and the question now is whether the institutions that know better will finally act accordingly.
Sepsis kills more people in intensive care units than most other conditions. Doctors have gotten better at spotting it early and treating it fast, yet something fundamental remains broken: the way we dose antibiotics almost entirely ignores who the patient is.
A new editorial in the Journal of Intensive Medicine, written by Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello, makes the case that biological sex and gender inequity are quietly undermining sepsis treatment across hospitals worldwide. The problem is not new, but it has been overlooked long enough that it now demands attention.
The body processes drugs differently depending on sex. Women have less muscle mass and different hormonal profiles than men. Their kidneys clear certain medications at different rates. Their metabolism works on a different timeline. Yet when a sepsis patient arrives in the emergency department, they receive the same antibiotic dose as everyone else in their weight category, regardless of these differences. The result is predictable and troubling: women tend to accumulate too much drug in their systems, raising the risk of toxicity and adverse reactions. Young men, by contrast, often eliminate antibiotics so rapidly that therapeutic levels never build up in their blood. They end up underdosed, and the infection persists.
Beyond the chemistry, gender shapes how sepsis patients are treated. Women are less likely to receive aggressive or timely interventions. Emergency departments may misinterpret their symptoms. Health care workers may harbor unconscious biases about the urgency of their condition. These social and institutional factors layer on top of the biological ones, compounding the harm. A woman arrives with sepsis already at a disadvantage—her body will process the antibiotic differently, and the system around her may move more slowly to help.
The authors point out that women remain underrepresented in the drug trials that establish dosing guidelines in the first place. Fewer than 30 percent of current studies even report their results broken down by sex. This means the evidence base itself is skewed. We are dosing half the population based on data that barely includes them.
The solution, according to the editorial, lies in two directions. First, hospitals should use therapeutic drug monitoring—measuring actual antibiotic levels in patients' blood and adjusting doses in real time based on what is actually happening in that person's body. This is not new technology. It works. It simply requires commitment and resources. Second, the research community needs to change how it designs and reports studies. Sex-stratified data should be standard, not exceptional. Future dosing protocols should be built on evidence that accounts for biological difference from the start.
Prof. Rello framed the issue as a matter of precision medicine and equity together. Understanding how sex and gender shape drug response is not just better science—it is a recognition that one-size-fits-all dosing has always been a compromise that harms some patients more than others. The question now is whether hospitals and researchers will act on what they already know.
Notable Quotes
Standard dosing overlooks key biological differences. 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.— Dr. Helena Barrasa, Dr. Goiatz Balziskueta, and Prof. Jordi Rello
Understanding the differences shaped by sex and gender is essential to advancing personalized medicine and represents a commitment to reducing the equity gap.— Prof. Jordi Rello
The Hearth Conversation Another angle on the story
Why does sepsis dosing still ignore sex when we've known about these differences for years?
Because sepsis protocols were built on a foundation of male-centered research and male-typical physiology. Once a standard gets written into guidelines, it becomes invisible—just "the way we do it." Changing it requires admitting the old way was incomplete.
But surely the risk of harming women would have surfaced by now in clinical practice?
It has. Women show up in adverse event reports, in ICU outcome data. But those signals get scattered across thousands of hospitals and never get connected to a single cause. A woman gets an allergic reaction to an antibiotic and it's recorded as an individual incident, not as evidence of a systemic dosing problem.
What would therapeutic drug monitoring actually look like in a busy ICU?
A blood draw, a lab test, a number back in a few hours. Then the pharmacist adjusts the next dose. It adds a step, but it replaces guessing with knowing. The hard part isn't the science—it's the workflow and the will to do it for every patient.
If young men are underdosed, why hasn't that caused a bigger outcry?
Because treatment failure in men often gets attributed to the infection being resistant or the patient being sicker, not to the dose being wrong. The bias works both ways—we notice women's adverse reactions but miss men's therapeutic failures.
What's the barrier to sex-stratified research?
Cost, mostly. Running a study that reports results separately for men and women means larger sample sizes. Journals have started requiring it, but funding agencies and sponsors have been slow to catch up. It's cheaper to pretend everyone is the same.