Study Examines Longitudinal Dynamics, Characteristics of Toxigenic C diff in Infants

Results of a large longitudinal cohort study revealed a high prevalence of toxigenic Clostridioides difficile carrier state in children. Colonization was also not linked with significant changes in microbial diversity in children, leading researchers to surmise the carrier state is most likely a transient component of the dynamic infant microbiome.

The prevalence of C diff has risen in recent years, and although its carriage is recognized in infancy, limited data exist on its longitudinal trends, associated epidemiological risk factors, and intestinal microbiome characteristics.

“Infants represent a unique cohort, as cross-sectional studies have shown a high C diff carrier state in infancy around 25% to 70% that approaches the adult carrier rate of 3% at around 8 years of age; although many of these studies did not differentiate toxigenic strains,” the authors explained. “Thus infants can be a potential reservoir for community spread of C diff, specifically if they have disease causing toxigenic strains.”

To address this knowledge gap, they investigated temporal changes in the prevalence of toxigenic C diff colonization in children up to age 2 years, publishing their findings in Gut Microbes.

Between April 2018 and August 2021, 2608 serial stool samples were collected from 817 children. Half of the infants included were male; 61% were born vaginally, and while 90% were full term. Just over 20% of mothers received prenatal antibiotics and 56% received perinatal antibiotics.

Analyses revealed:

• Toxigenic C diff was detected in 1% of meconium samples and 19% of 2-month, 37% of 6-month, 40% of 12-month, and 8% of 24-month samples
• Infants receiving any breast milk at 6 months were less likely to be carriers at 2 , 6, and 12 months vs those not receiving it (P = .002, P < .0001, and P = .022, respectively)
• There were no robust differences in the underlying alpha or beta diversity between those with and without toxigenic C diff carriage at any timepoint, although small differences in the relative abundance of certain taxa were found

In addition, infants with non-Hispanic mothers were more likely to be positive than those with Hispanic mothers at 12 months. Those born to mothers with more than the recommended weight gain during pregnancy were also more likely to be positive at ages 6 months and 1 year.

The antimicrobial properties of breast milk likely contributed to low carrier rates seen in the group that was breastfed, the authors noted.

The study is the largest longitudinal one to date on the epidemiology of toxigenic C diff carriage in children up to 2 years and its intestinal microbiome associations.

Overall, “a high prevalence rate was noted, with a peak of 40% at 12 months.” Although findings were consistent with past studies, the authors noted the much higher prevalence rate reported at 12 months could be due to the increase of its prevalence over time, geographic variations in distribution, and study design differences. C diff detection techniques could have also varied.

“The very low prevalence of C diff in meconium samples and the steady increase during rest of infancy suggests that it is most likely environmentally acquired rather than maternally transmitted at birth; however, maternal C diff status at delivery was not obtained to confirm this hypothesis,” the authors added.

Those who tested positive in earlier samples were also more likely to again test positive, suggesting C diff persists after its initial colonization. This finding could also mean infants could act as a significant reservoir for community spread of toxigenic C diff.

The study was carried out at a single center, meaning findings may not be generalizable to other regions of the world. Most infants included were also carried to term, and the prevalence rate recorded may not be indicative of distribution in preterm infants.

Reference

Mani J, Levy S, Angelova A, et al. Epidemiological and microbiome associations of Clostridioides difficile carriage in infancy and early childhood. Gut Microbes. Published online April 25, 2023. doi:10.1080/19490976.2023.2203969