Temporal burden of WHO Critical-priority Enterobacteriaceae in the infant gut during early life influenced by maternal postpartum antibiotic exposure

Purpose: Antimicrobial resistance (AMR) in the gut microbiome progressively evolves during infancy. This study aimed to evaluate the prevalence of WHO Critical Priority Enterobacteriaceae in infants’ gut commensals and investigate the factors associated with the development of AMR. Methods: Stool samples were collected from 67 infants at birth, 6-weeks and 14-weeks. E. coli, Klebsiella pneumoniae and Enterobacter species were isolated and tested for susceptibility to 22 antibiotics and screened for extended-spectrum beta-lactamase (ESBL) production. Chi-square test and logistic regression tests were performed to evaluate the influence of clinical and demographic factors on the carriage of drug-resistant Enterobacteriaceae. Results: Of the 67 infants, stool samples from 38 infants (58.4 %) yielded 200 isolates of Enterobacteriaceae across three-timepoints. E. coli was predominant at 6-weeks (53%) and 14-weeks (63%). Cephalosporin resistance peaked at 6-weeks, with E. coli showing the highest resistance to 3^rd (43%) and 4^th (38%) generation cephalosporins. ESBL production was highest at 6-weeks, with 40% of E. coli producing ESBL, and 34% of infants carrying ESBL-producing strains. Maternal postpartum cephalosporin use significantly increased the likelihood of infants carrying cephalosporin-resistant Enterobacteriaceae (p-value = 0.001; OR: 10.4; 95% CI: 2.31–46.83), ESBL-producers (p-value = 0.009), and multidrug-resistant isolates (p-value = 0.027). Conclusion: These findings highlight that cephalosporin-resistant Enterobacteriaceae colonize the infant gut as early as 6-weeks, with maternal postpartum antibiotic exposure playing a significant role. Understanding these early-life drivers of AMR could help inform strategies to mitigate AMR spread in vulnerable populations.