High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples

Abstract

The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to β-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies' mothers, as well as a mother-infant series including meconium, fecal samples collected through the infant's 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds' samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant's GIT as a noteworthy reservoir of this gene.

Antibiotic treatment at delivery shapes the initial oral microbiome in neonates

“…Maternal antibiotic exposure was associated with expression of carbapenem-hydrolyzing enzymes of the Vim -1 gene in 6 of 23 neonates that received antibiotics. Previous studies have also reported the presence of Vim -type genes in infants4950. Carbapenem-resistant isolates of Pseudomonas aeruginosa and other gram-negative non-fermenters have been identified to be Vim -1-containing microorganisms51.…”

Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates

“…Given the potential role of the gut microbiota as reservoir for antibiotic resistance genes, the early microbiota establishment may also constitute a critical step from this perspective. Some studies have reported the presence of antibiotic resistance genes in the early life microbiota [49, 50]. Gosalbes and co-workers [50] demonstrated the presence of genes conferring resistance to β-lactam antibiotics and tetracycline in the meconium of more than half of the newborns.…”

The Eukaryotic Microbiome: Origins and Implications for Fetal and Neonatal Life

“…This microbial profile strongly resembles that of young infants, but importantly is significantly influenced by a range of maternal factors. For example, maternal eczema has been linked to newborn respiratory disorders (51). Therefore, there is a necessary overlap of the maternal immune system with that of the fetus and this extends beyond the direct innate maternal mechanisms that were previously assumed to be the only operative ones.…”

“…It also becomes clear that the development of that “organ” is a function of a significant overlap with the maternal microbiome. For example, Gosalbes et al used culture-independent genetic screening to demonstrate a high incidence of maternally transferred antibiotic-resistant genes in infant’s meconium and fecal samples, at least some of which is presumed to have occurred in utero (51). …”