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.
Highlights
Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacterium, responsible for 15–25% of all cases of antibiotic-associated diarrhea [1]
In the ClosNEC cohort, of the 159 stool samples analyzed by culture, 37 (23%) were C. difficile positive
Additional data were collected by characterizing C. difficile strains from two other multicentric preterm neonates (PN) cohorts (ClosNEC and EPIFLORE)
Summary
Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacterium, responsible for 15–25% of all cases of antibiotic-associated diarrhea [1]. Clinical presentations of C. difficile infections (CDI) range from mild self-limited diarrhea to severe pseudomembranous colitis. Risk factors for CDI include host-related factors (e.g., advanced age, comorbidities, immunodepression), factors causing a gut dysbiosis (e.g., use of antibiotics, proton-pump inhibitors) and factors exposing to C. difficile spores (e.g., long hospital stay, contaminated environment) [2,3]. The CDI incidence has significantly increased for the past two decades, in healthcare facilities as well as in community settings [4]. The emergence and spread of a hypervirulent epidemic strain called 027/B-I/NAPI partly explains this epidemiological shift. C. difficile virulence is mainly based on the production of two potent toxins, TcdA and TcdB
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