Prolonged antibiotic use in preterm infants has long-lasting effects

Gautam Dantas, PhD,

Antimicrobial resistance is a growing concern, and a recent study confirms that long-term antibiotic use can spur the development of drug-resistant bacteria in infants.

The study, published in Nature Microbiology, reveals that treating preterm infants with antibiotics for more than 20 months results in the development of multi-drug resistant gut bacteria. The study analyzed stool samples from 32 preterm infants treated with antibiotics for 21 months and compared them to stool samples of infants who received shorter courses of antibiotics or none at all. The study, funded by the National Institutes of Health, found that infants treated with long-term antibiotics had less diverse gut microbiota, and that these bacteria were equipped with more antibiotic resistant genes. Additionally, researchers found that the infants treated with more antibiotics showed resistance to antibiotics not typically given to infants, including ciprofloxacin and chloramphenicol. The study suggests this may be due to some antibiotics triggering resistance to others, even when they are not used.

Gautam Dantas, PhD, professor of pathology and immunology at the Washington University School of Medicine in St. Louis, Missouri, and co-author of the study, says the effects noted in the study may be long-lasting. He was particularly surprised at the duration of the microbiota response to antibiotics. The microbiota of antibiotic-treated and hospitalized infants was distinguishable from that of healthy term infants even months after discharge from the neonatal intensive care unit (NICU), he adds.

 “We found that antibiotic treatment and extended hospitalization perturbs the microbiota of extremely and very preterm infants, and that this perturbation, which is characterized by persistent carriage of Enterobacteriaceae and an enriched antibiotic resistome, is still evident months following discharge from the NICU,” Dantas says. “This means that antibiotic exposures very early in life may have life-long consequences in terms of microbiome health and the risk of carriage of drug resistant bacteria.”

Dantas says providers should realize the risks of prolonged antibiotic use and take action.

“The long lasting effect on gut microbial content after administering early-in-life antibiotics is sobering. This collateral ecologic damage certainly has ramifications for physicians caring for infants born preterm,” Dantas says. “Our data also raise the possibility that antibiotics similarly affect gut bacteria in other childhood populations. In any event, our findings lend additional support to worldwide efforts to use antibiotic as wisely as possible in all areas of medicine.”

The findings are particularly important for pediatricians caring for the most vulnerable infants, Dantas says.

“Neonatologists in particular should be cognizant of the collateral damage of broad spectrum antibiotic treatment. In the past practitioners saw very little risk to using antibiotics, and antibiotic treatment is often necessary, especially in very and extremely premature infants,” Dantas says. “However, we encourage steps to limit unnecessary initiation of antibiotics, and to reduce, wherever possible, the duration of such treatments.”

Dantas plans to continue his research, investigating in greater depth the long-term effects of prolonged antibiotic use.

“One important next step for this research is to follow hospitalized premature infants throughout childhood to determine the durability of antibiotic and hospitalization induced perturbations to the microbiota,” he says. “Further, studies involving greater numbers of extremely and very preterm infants not treated with antibiotics-a population becoming increasingly available for sampling as treatment regimens change-might elucidate the specific effects of antibiotics on the microbiota.”