Giving healthy kids antibiotics saves lives. There’s a catch.

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The sharp decline in child mortality rates is one of the great global success stories of the past several decades.

In 1990, nearly 13 million children died before their fifth birthday, primarily from infectious diseases or complications during birth. By 2022, that number had fallen by more than 50 percent, meaning that today, about 8 million fewer children are dying than were some 35 years ago.

Overall development improvements, alongside a handful of targeted public health interventions — ensuring that skilled health care workers are present during childbirth, improving access to clean water, providing postnatal care, and expanding vaccination, to name a few — have helped ensure far more children live to see their fifth birthday and beyond.

Yet despite that progress, around 5 million children younger than 5 years old still die prematurely each year, with about 80 percent of those deaths occurring in sub-Saharan Africa and southern Asia. And progress to reduce child mortality has slowed in recent years. Between 2015 and 2022, child mortality rates fell by only 2 percent, down from about 4 percent between 2000 and 2015.

But one surprising intervention — periodically distributing antibiotics prophylactically to young children en masse — could help further reduce child mortality rates in some of the worst-affected countries. A study published in August examined children in Niger, a country in West Africa with one of the highest child mortality rates in the world. Researchers found that twice-yearly mass distributions of an antibiotic to children between the ages of 1 and 5 reduced child mortality by 14 percent.

If this sounds too good to be true — significant reductions in child deaths simply by giving them basic drugs designed to fight bacterial infections — it may be. This intervention around one major health challenge — childhood mortality — is somewhat controversial because it seems to directly run against another major health challenge: the rise of drug-resistant infections. Such infections, which are caused by the overuse of antibiotics, claim an estimated 1 million lives every year, a number that could nearly double by 2050.

“If you increase the amount of antibiotic exposure in the population, you are guaranteed to increase the risk of having drug resistance,” said Gautam Dantas, a professor at Washington University’s School of Medicine who studies the human microbiome and antimicrobial resistance. These drug-resistant pathogens can spread around the world, creating a public health threat for everyone.

And there’s another question: While the positive results show promise, no one is exactly sure why giving antibiotics to children who have no overt sign of infection but still live in high-risk areas reduces overall child mortality in the community.

Given the unknowns and potential to contribute to global drug resistance, the World Health Organization in 2020 strongly recommended against mass antibiotic distribution as a universal intervention. Instead, the agency suggested that public health officials pursue the intervention only in places where under 5 mortality is greater than 80 children per 1,000 births. In 2022, only 10 countries recorded under 5 mortality rates higher than this threshold.

The scientists who study and advocate for the mass distribution of antibiotics are well aware of these issues. The essential question: How does one weigh saving children’s lives against fueling another deadly health threat?

The idea of mass distributing antibiotics to reduce child mortality has its origins in control programs for a specific disease: trachoma. Trachoma is a bacterial eye infection that can lead to visual impairment and irreversible blindness.

Though the disease has plagued humanity for at least 10,000 years, by the early 20th century it had become a serious scourge, infecting anyone from soldiers to boarding school students. But the disease was wiped out in most developed countries in the 1950s and 1960s following the invention and widespread use of antibiotics, especially azithromycin.

But trachoma has persisted in about 50 countries, mostly in poor, rural areas of Africa, Asia, the Middle East, as well as Central and South America. About 2 million people today have blindness or visual impairment caused by trachoma and another 103 million are considered at risk of contracting the disease.

In communities where trachoma is still a problem, the disease prevalence is high, ranging from 60 to 90 percent. Because trachoma became so widespread, the World Health Organization in the early 1990s recommended that health officials treat everyone in an affected community with the antibiotic azithromycin, whether or not they had been diagnosed with the disease. The thinking was that treating the entire community with an antibiotic would reduce the amount of bacteria circulating in the community, thus reducing transmission — much like mass vaccination is used to curtail viral outbreaks.

In the early 2000s, researchers started noticing that mass distribution of azithromycin not only reduced trachoma, but also seemed to reduce overall child mortality. Scientists running a trachoma control study in Ethiopia hypothesized that because azithromycin was effective against other infectious diseases, including respiratory and diarrheal diseases and malaria — all leading causes of childhood death in the country — mass distribution of the drug might help save children’s lives.

Other public health scientists probed this idea further by conducting mass antibiotic distribution trials in places where trachoma wasn’t found.

In one 2018 study known as the MORDOR trial (MORDOR stands for Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance, French for “Oral Macrolides to Reduce Deaths with an Eye on Resistance”), researchers randomly selected more than 1,000 villages across Malawi, Niger, and Tanzania to either receive the mass distribution of azithromycin or a placebo intervention. Children who were between one month and five years in the intervention villages received a small dose of azithromycin twice a year for two years.

At the end of the study, in communities where children had received the antibiotic, the overall annual mortality rate was lower — by about 3 percent in Tanzania, 6 percent in Malawi, and 18 percent in Niger — compared to the villages that received a placebo. The drop in mortality was even greater, about 25 percent, among the youngest children, those between 1 and 5 months old.

While the results are promising, researchers still do not fully understand how mass azithromycin distribution reduces child mortality. One explanation is that the intervention works in a similar way as it does in trachoma-endemic settings, but instead of providing communities a blanket of protection against merely the Chlamydia trachomatis bacterium that causes trachoma, it bestows protection against a wider range of bacteria, including the ones that cause the common respiratory diseases and diarrheal diseases that can kill young children in poor countries.

“It may not be just that you get lucky and you treat a kid that happens to be sick that week,” said Thomas Lietman, a professor at the Proctor Foundation at the University of California, San Francisco who has led studies on trachoma and was the senior author of the 2018 and 2024 child mortality studies.

“We think it’s that we’re reducing the pathogen load in the community. And one of the reasons we think this is because there appears to be an indirect effect. In other words, you receive benefit just by your community being treated.”

Even during these early trials, researchers were concerned about how giving antibiotics to kids might fuel another massive global challenge: antimicrobial resistance, the process by which bacteria evolve the ability to evade antibiotics. It’s simply a matter of evolution: the more that antimicrobials are used, the more opportunities pathogens have to develop resistance to them. If that process continues long enough, it will eventually render these critical, life-saving medicines ineffective.

At the same time, most major drug developers have turned away from making new antibiotics. That means our stores of effective antibiotics are dwindling. If left unchecked, researchers predict that some 2 million people might die from drug-resistant infections by 2050, making it a leading cause of death. But people won’t just die from drug-resistant infections. Life-saving surgeries and treatments such as chemotherapy, which massively damage the immune system, will become much riskier because it will be harder to prevent infections..

In its antibiotic stewardship guidelines, the Centers for Disease Control and Prevention recommends that health care workers only prescribe antimicrobials if they know what pathogen is causing a patient’s illness. But the idea of mass distributing antibiotics to reduce childhood mortality runs entirely counter to that.

“We’re taught in every health care field not to give antibiotics non-specifically; yet that’s exactly what we’re doing here,” Lietman said. “We’re giving antibiotics to children whether or not they’re sick, whether or not they have a particular pathogen.”

However, it is unclear what impact mass distribution interventions have on drug resistance. After the MORDOR trial, researchers conducted follow-up studies where they collected swab samples from the children who received the antibiotic during the study and those who did not. Among children who participated in the study in Tanzania, researchers reported that there was no significant difference in the number of azithromycin-resistant strains of two types of bacteria between the two groups. Yet in Niger, researchers found that children who received the antibiotic harbored more drug-resistant strains.

Other studies, though not all, that have assessed drug resistance in the wake of mass distribution campaigns for trachoma control have documented measurable but short-lived increases in drug-resistant bacterial strains.

Regardless of whether and to what extent mass antibiotic distribution contributes to drug resistance, the intervention uses a small fraction of the total antibiotics consumed worldwide either by humans or livestock animals. In the 2018 MORDOR study, children received about 20 milligrams per kilogram of body weight which equates to about 360 milligrams for a 40-pound child or a total of, at most, 36 kilograms of antibiotics for the roughly 100,000 children that received the intervention across four distributions.

Compare that to, say, the 6.2 million kilograms of medically important antibiotics sold for use in livestock operations in the US in 2022. Perhaps it would be more effective to reduce antibiotic use in agriculture than target relatively miniscule antibiotic use during an intervention that saves children’s lives.

But there may be other consequences to mass antibiotic use. A series of studies conducted mostly in the US and Europe have linked antibiotic use in childhood with an increased risk of developing obesity, attention deficit hyperactivity disorder, asthma, and other lifelong disorders.

Still, it is important to note here that these studies are looking at a very different population than children in Niger who face a high risk of dying before they turn 5. Some research suggests the link between antibiotic use and obesity and other disorders may be related to alterations in the gut microbiome, but it remains unclear exactly how antibiotics might cause poor health outcomes and what role other lifestyle factors might play. And those factors could be entirely different in a country like Niger or Tanzania than in the US.

“Right now, the benefit outweighs the harm,” Dantas said. “Yes, you may encode some burden elsewhere, but you’ll save the life of a child.”

It’s hard to argue that saving thousands — if not millions — of children’s lives doesn’t outweigh future threats of drug resistance or a possible heightened risk of developing chronic diseases. There are plenty of other ways to address the public health challenges posed by antibiotic resistance and chronic diseases that don’t put the lives of some of the poorest children in the world at risk.

And there is one conclusion that is undeniable: If millions of young children were dying every year in the US, parents would demand that every possible intervention be used — whatever the future consequences.