The association between early life antibiotic exposure and the gut resistome of young children: a systematic review

Abstract

Antimicrobial resistance is a growing public health burden, but little is known about the effects of antibiotic exposure on the gut resistome. As childhood (0-5 years) represents a sensitive window of microbiome development and a time of relatively high antibiotic use, the aims of this systematic review were to evaluate the effects of antibiotic exposure on the gut resistome of young children and identify knowledge gaps. We searched PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials. A PICO framework was developed to determine eligibility criteria. Our main outcomes were the mean or median difference in overall resistance gene load and resistome alpha diversity by antibiotic exposure groups. Bias assessment was completed using RoB 2 and ROBINS-I with quality of evidence assessed via the GRADE criteria. From 4885 records identified, 14 studies (3 randomized controlled trials and 11 observational studies) were included in the qualitative review. Eight studies that included information on antibiotic exposure and overall resistance gene load reported no or positive associations. Inconsistent associations were identified for the nine studies that assessed resistome alpha diversity. We identified three main groups of studies based on study design, location, participants, antibiotic exposures, and indication for antibiotics. Overall, the quality of evidence for our main outcomes was rated low or very low, mainly due to potential bias from the selective of reporting results and confounding. We found evidence that antibiotic exposure is associated with changes to the overall gut resistance gene load of children and may influence the diversity of antimicrobial resistance genes. Given the overall quality of the studies, more research is needed to assess how antibiotics impact the resistome of other populations. Nonetheless, this evidence indicates that the gut resistome is worthwhile to consider for antibiotic prescribing practices.

Keywords: Antibiotics; antibiotic resistance genes; children; resistome; systematic review.

Figure 1.

PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers, and other sources.

Figure 2.

Assessment of potential bias sources for included a) randomized controlled trials and b) observational studies. Randomized controlled trials were assessed using the RoB 2 tool while observational studies were assessed using ROBINS-I.