Effect of Antimicrobial Exposure on Clostridioides difficile (C. difficile) Colonization of the Infant Gut Microbiota in the Canadian Healthy Infant Longitudinal Development (CHILD) Birth Cohort

Abstract

Introduction: Antimicrobial exposure in early life has been associated with gut microbiota dysbiosis and development of allergic diseases in childhood. In adults and older children, C. difficile is the major pathogen responsible for antibiotic-induced diarrhea but the effect of colonization with this bacterium in infants is unclear. About 30% of infants are colonized with C. difficile without the presence of clinical symptoms, infection or diarrhea. However, colonization with this bacterium in infancy has been linked to development of asthma and allergic diseases later in life. The aim of this study was to determine the separate and cumulative impact from antibiotics and environmental antimicrobials (household cleaning products) on C. difficile colonization in infants. Methods: This study population comprises of a representative sample of mothers and infants who were successfully enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Infant antimicrobial exposure was obtained from hospital birth chart (maternal intrapartum antibiotic (IAP) and newborn intravenous antibiotic) and standardized questionnaires (infant oral antibiotic and household cleaning product use). Exposure to household cleaning products was based on frequency of use and split at median into lower and higher use. Fecal samples were collected at 3 and 12 months after home assessment. Analysis of C. difficile was performed using quantitative polymerase chain reaction (qPCR) with appropriate primers. Logistic regression analysis was used to determine the crude and adjusted association between antimicrobial exposure and C. difficile colonization. Results: In this study, 44% of infants were indirectly exposed to antibiotics via maternal IAP, 8% directly received an oral or intravenous antibiotic and 47% lived in households with higher cleaning products use by 3 months. Infants were classified into 4 groups depending on antimicrobial exposure: no antibiotics and lower cleaning products use (NALC), any antibiotics and lower cleaning products use (AALC), no antibiotics and higher cleaning products use (NAHC), any antibiotics and higher cleaning products use (AAHC). At 3 months, C. difficile colonization was significantly higher in AALC, NAHC and AAHC infants compared to NALC infants. After adjusting for covariates, the increased odds of C. difficile colonization remained significant in the AAHC infants (aOR 1.50 95% CI 1.03-2.17; p=0.032). At 12 months, C. difficile colonization was significantly higher in only the AALC and AAHC infants compared to NALC infants in both crude and adjusted analysis (aOR: 1.36 95% CI 1.02-1.83; p=0.035 for AALC and aOR: 1.37 95% CI 1.00-1.86; p=0.043 for AAHC) Conclusion: Colonization with C. difficile as well as antimicrobial exposure in early infancy has been linked to increased risk of asthma and allergy. Our study suggests that cumulative exposure to antibiotics and higher household cleaning products use is not without consequence. Hence, the effect of antimicrobial exposure on the infant gut should be considered because colonization with C. difficile may be a marker for future health outcomes.