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Characterization of Non-Toxigenic Clostridioides difficile Strains Isolated from Preterm Neonates and In Vivo Study
Jeanne Couturier1,2, Léa Franconeri2, Claire Janoir3
1Faculty of Pharmacy, Paris University, INSERM UMR S-1139, 4 Avenue de l'Observatoire, 75006 Paris, France.
Insights
Two uncommon non-toxigenic Clostridioides difficile strains (NTCD) were prevalent in preterm neonates. These NTCD strains demonstrated a protective effect against C. difficile infection in a hamster model.
Area of Science:
- Microbiology
- Neonatal Health
- Infectious Diseases
Background:
- A previous study found high Clostridioides difficile colonization in preterm neonates (PN) with two uncommon non-toxigenic strains (NTCD): PCR-ribotype (RT) (CE)847 and (CE)032.
- The prevalence and protective potential of these specific NTCD strains in broader settings were unknown.
Purpose of the Study:
- To investigate the carriage of two specific NTCD strains (RT (CE)847 and (CE)032) in preterm neonates across multiple centers.
- To evaluate the protective efficacy of these NTCD strains against Clostridioides difficile infection using a hamster model.
Main Methods:
- Strains from preterm neonate stools (n=247) in two multicenter cohorts were characterized using PCR-ribotyping, MLVA, and MLST.
- A hamster caecitis model was used to assess protection against a toxigenic C. difficile (027 strain) after administration of either RT (CE)847 or (CE)032 NTCD.
Main Results:
- Eighteen RT (CE)032 (ST-83) strains and two RT (CE)847 (ST-26) strains were identified among 247 preterm neonates.
- Animals pre-treated with either NTCD strain showed significantly increased survival rates when subsequently challenged with the toxigenic C. difficile 027 strain compared to controls.
Conclusions:
- Two uncommon non-toxigenic Clostridioides difficile strains (RT (CE)847 and (CE)032) are predominant in preterm neonates across different healthcare facilities.
- These specific NTCD strains offer potential protection against C. difficile infection, suggesting a possible role in infection prevention strategies.
Abstract:
In a previous monocentric study in preterm neonates (PN), we described a high Clostridioides difficile colonization rate (74%) with two uncommon non-toxigenic strains (NTCD) belonging to PCR-ribotype (RT) (CE)847 and (CE)032. To determine the extent of carriage of both NTCD in other spatio-temporal settings, strains isolated in PN stools from two multicenter cohorts were characterized by PCR-ribotyping, MLVA and MLST. We also evaluated the protective role of two NTCD from these RT against C. difficile infection in a hamster caecitis model. Animals were administered either each NTCD alone (n = 7), or followed by a 027 strain (n = 9). A control group received only the 027 strain (n = 8). Clinical activity and colonization by C. difficile in stools were monitored daily until death or sacrifice at D20. We isolated 18 RT(CE)032 (ST-83) strains and 2 RT(CE)847 (ST-26) strains among 247 PN from both cohorts. Within each RT, strains were genetically related. The survival rate was significantly increased when animals received a RT(CE)847 or (CE)032 strain before the 027 strain (4/9 deaths, p = 0.029; 1/9 death, p = 0.0004, respectively). We describe two predominant uncommon NTCD strains, in a PN population from different healthcare facilities. Both NTCD provide a potential protection against C. difficile infection.
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