SAN DIEGO (FRONTLINE MEDICAL NEWS)As little as 2-3 days of neonatal antibiotic exposure are sufficient to disrupt the development of the gut microbiota at 1 and 6 months of age, according to a case-control study.

The study design enabled investigators to conclude that the aberrant gut colonization was due to the brief course of antibiotics rather than the supposed infection for which the drugs were prescribed, Dr. Samuli Rautava said at the annual meeting of the Pediatric Academic Societies.

“I’m surprised that all of the effects on the microbiota we see are more prominent at 6 months of age than at 1 month. We do not have direct evidence that these relatively long-term perturbations of the gut microbiota lead to increased risk of disease, but if you go through the literature, I think it’s worrisome,” said Dr. Rautava, a pediatrician at the University of Turku (Finland).

He noted that prior studies have linked early antibiotic exposure to increased risks of developing necrotizing enterocolitis, asthma, inflammatory bowel disease, and most recently obesity ( Pediatrics 2015;135:617-26 ).

Dr. Rautava reported on a prospective comparison of gut microbiota development in 36 term or late-preterm infants. The study population consisted of 6 infants with a documented infection for which they received a 7-day course of gentamicin or penicillin G beginning within the first 3 days after birth, 6 infants who received the same drugs on an empiric basis for up to 2-3 days before treatment was discontinued because infection had been ruled out, and 24 non–antibiotic exposed controls matched for duration of breastfeeding, mode of birth, and maternal use of probiotics.

The purpose of the study was to tease out the relative impact on gut microbiota development of early antibiotic exposure versus the infections for which the drugs are given. Gut microbiota composition was analyzed from fecal samples assessed at 1 and 6 months of age by quantitative polymerase chain reaction, 16S rRNA pyrosequencing, and denaturing gradient gel electrophoresis.

Among the key findings: Both groups of antibiotic-exposed neonates had markedly low levels of Bifidobacterium species, including B. bifidum, at 1 and 6 months. These are “good” gut microbes, and low levels early in life have been associated with obesity and allergies.

Bacteroides species were virtually absent at 1 month of age in both groups with early antibiotic exposure. Again, low levels early in life have been linked to obesity and allergies.

“The situation is a little better at age 6 months, but there is still some scarcity of Bacteroides species in these infants at that time,” according to the pediatrician.

In contrast, Clostridium species are more abundant in the gut microbiota of antibiotic-exposed children at both 1 and 6 months than in controls. This makes sense, since gentamicin and penicillin G are not effective against Clostridium species, which have been linked to disease.

Dr. Rautava said these study findings have significant implications for clinical practice: “We cannot not give antibiotics to infants who might have sepsis, but we need to develop means of finding the bacterially infected neonates who truly need the antibiotics so we can avoid unnecessary antibiotic exposure during this vulnerable period.”

“I told my post-doc when we did this study that the scientist in me wants to see huge changes in the gut microbiota, but the clinician in me wants to see no changes at all. So I’m torn: I’m happy to have something to report, but I’m devastated at what we’re actually doing with our early antibiotic therapy,” Dr. Rautava said.

Dr. Rautava’s study was funded by the University of Turku and other noncommercial sources. He reported having no financial conflicts.