The landscape of antibiotic resistance genes in the nasopharynx of preterm infants: Prolonged signature of hospitalization and effects by antibiotics

ABSTRACT Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. Utilizing shotgun metagenomics, we investigated the nasopharynx resistome development in preterm infants, assessed early antibiotic impact on its trajectory, and explored its association with clinical covariates. Our findings revealed widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persisted up to 8-10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlated with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.