Resistant Bacteria Found in Preterm Infants After Prolonged Antibiotic Treatment

Prolonged antibiotic treatment in preterm infants may cause lasting changes to the microbiome, according to a new study that found evidence of multidrug-resistant gut bacteria in infants treated during the first months of life.

The study, published in the journal Nature Microbiology, followed 58 infants through the first 21 months of life, using DNA sequencing to examine fecal samples. The study, funded by the National Institutes of Health, included 32 infants born very preterm who received extensive antibiotics during the 21-month study period, 9 preterm infants who received antibiotics for less than a week and 17 healthy full-term infants who didn’t receive antibiotics.

“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,” study authors Andrew Gasparrini, PhD, who was a graduate student during the study, and Phillip Tarr, MD, the Melvin E. Carnahan professor of pediatrics at Washington University School of Medicine, told Contagion^®.

Preterm infants who received prolonged antibiotics developed diverse microbiotas more slowly, and they were dominated by more harmful drug-resistant proteobacteria than those with light or no treatment. Even at 21 months, the disruptions to the microbiome were noticeable.

“We were surprised by the duration of the microbiota response to antibiotics,” Gasparrini and Tarr said. “It was notable that the microbiota of antibiotic-treated and hospitalized preterm infants was distinguishable from that of healthy term infants even months following NICU discharge.”

Nearly all preterm infants are prescribed antibiotics to treat or ward off infections.

As antimicrobial-resistant microbes continue to challenge health officials, antibiotic stewardship programs are gaining more attention. Previous studies have estimated that about 50% of antibiotic prescriptions are unnecessary or inappropriate. As a result, some research teams are exploring new options to help guide antibiotic use and promote stewardship such as building alerts into electronic medical records systems.

The role of the gut microbiota also is drawing more attention, with some considering it an “essential organ” with a vital role in maintaining health.

“The long-lasting effect on gut microbial content after administering early-in-life antibiotics is sobering,” Tarr and Gasparrini told Contagion^®. “This collateral ecologic damage certainly has ramifications for physicians caring for infants born preterm. 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.”

While the study was unable to isolate for other possible factors such as extended hospitalizations and illness, the investigators noted previous studies that found a link between antibiotic treatment during infancy and health issues later in life, including allergies, psoriasis, diabetes and inflammatory bowel disease.

“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). However, we encourage steps to limit unnecessary initiation of antibiotics, and to reduce, wherever possible, the duration of such treatments.”

Further research is needed, including following preterm infants throughout childhood, to monitor the microbiota over time. Research to examine preterm infants not treated with antibiotics also may shed light on the effects of antibiotics, and animal studies might help investigators better understand whether and to what extent antibiotics in early life affect health concerns later in life.