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The relationship between antibiotic use and Clostridioides difficile ( C. difficile ) has been well established in adults and older children but remains unclear and is yet to be fully examined in infant populations. This study aimed to determine the separate and cumulative impact from antibiotics and household cleaning products on C. difficile colonization in infants. This study included 1429 infants at 3-4 months of age and 1728 infants at 12 months of age from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. The levels of infant antimicrobial exposure were obtained from hospital birth charts and standardized questionnaires. Infant gut microbiota was characterized by Illumina 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Analysis of C. difficile was performed using a quantitative polymerase chain reaction (qPCR). Overall, C. difficile colonized 31% and 46% of infants at 3-4 months and 12 months, respectively. At 3-4 months, C. difficile colonization was significantly higher in infants exposed to both antibiotics and higher (above average) usage of household cleaning products (adjusted odds ratio (aOR) 1.50, 95% CI 1.03-2.17; p = 0.032) than in infants who had the least antimicrobial exposure. This higher colonization persisted up to 12 months of age. Our study suggests that cumulative exposure to systemic antibiotics and higher usage of household cleaning products facilitates C. difficile colonization in infants. Further research is needed to understand the future health impacts.

Introduction: Greater prescribing of antibiotics to infants has coincided with an epidemic of allergic disease. Through meta-analytic synthesis, accumulating evidence from prospective or database cohorts suggests a link between infant antibiotic treatment and the development of atopy. Stronger associations seen with multiple course and broad-spectrum antibiotic treatment add to biological plausibility. A major bias, confounding by indication, has been addressed in studies on antibiotic treatment of conditions which do not precede allergic disease. Areas covered: Our review provides an up-to-date synthesis of the current literature on associations between infant antibiotic exposure and future allergic disease. We discuss methods that assist in reducing study bias and look at new insights from studies of the infant gut microbiome. Expert commentary: Large-scale profiling of the gut microbiome provides a new tool for disentangling biases found in observational studies of infant antibiotic use. To date, microbial dysbiosis of the infant gut has been reported to predict allergic disease independent of antibiotic exposure up to 3 months after birth. However, these studies have not accounted for antibiotic treatment in later infancy. Continued study of the infant gut microbiome, mycobiome, or resistome will provide a closer link to antibiotic treatment or refute it as a cause of allergic disease.