The neonatal intestinal resistome and factors that influence it—a systematic review

Background The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors than the established microbiome in later life. Objectives In this review, we systematically summarize studies which investigated the intestinal resistome in neonates. Data sources MEDLINE and Embase databases were searched. Study eligibility criteria We included original studies which investigated ARGs in stool or rectal swabs in neonates using molecular diagnostics. Methods of data synthesis Two authors independently extracted data, which were summarized in tables. Results Our search identified 2701 studies, of which 23 (22 cohorts) were included. The studies show that the neonatal intestine harbours a high abundance and variety of ARGs, even in the absence of direct antibiotic exposure. The most commonly found ARGs confer resistance to aminoglycosides, β-lactams, macrolides, tetracyclines, or multidrug resistance. There is evidence that ARGs can be transferred from mothers to neonates. Interestingly, however, compared to mothers, neonates are reported to have a higher abundance of ARGs. One likely reason for this is the bacterial phylogenetic composition with a high abundance of Gammaproteobacteria in neonatal stool. Factors that have been associated with a higher abundance of ARGs are intrapartum and neonatal antibiotic use. Breastfeeding and neonatal probiotic use have been associated with a lower abundance of ARGs. Antibiotics during pregnancy, delivery mode, or sex are reported to have little effect. However, this might be because studies were underpowered and because it is difficult to account for effect modifiers. Conclusions The neonatal intestine seems to have a lower colonization resistance, which could make it easier for antibiotic-resistant populations to establish themselves. Future studies will help in the development of evidence-based interventions to modulate the abundance of ARGs in neonates, for example, by the use of pre- and probiotics and bacteriophages.