Background: An epidemic strain of Clostridium difficile designated by restriction endonuclease analysis (REA) as group BI has caused multiple outbreaks of severe C. difficile infection (CDI). The treatment response of patients infected with this strain is uncertain.
Methods: Clostridium difficile isolates were collected from 2 phase 3 clinical trials comparing fidaxomicin to vancomycin and typed using REA. Clinical cure and recurrence outcomes were analyzed by strain type of the infecting organism, BI and non-BI, using both univariate and multivariate analyses.
Results: From 999 patients, 719 isolates were available for typing (356 fidaxomicin treated and 363 vancomycin treated). BI was the most common REA group (34% of isolates). Patients infected with BI had lower cure rates (86.6%; 214 of 247) than those infected with non-BI strains (94.3%; 445 of 472) (P < .001). The cure rate difference between the BI and non-BI patients was significant for both vancomycin (P = .02) and fidaxomicin (P = .007). BI patients had a recurrence rate of 27.4% (51 of 186), compared with a recurrence rate of 16.6% (66 of 397) in non-BI patients (P = .002). By multivariate analysis, BI infection was statistically significant as a risk factor for reduced cure (odds ratio [OR], 0.48; 95% confidence interval [CI], .27-.85; P = .030) and for increased recurrence (OR, 1.57; 95% CI, 1.01-2.45; P = .046).
Conclusions: The clinical cure rate of patients infected with the epidemic BI C. difficile strain is lower than the cure rate of those infected with non-BI strains whether treated with fidaxomicin or vancomycin. Similarly, the CDI recurrence rate is increased in patients with the BI strain compared with patients with other C. difficile strains.
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http://dx.doi.org/10.1093/cid/cis430 | DOI Listing |
Ann Biol Clin (Paris)
January 2025
Laboratoire Clostridioides difficile associé au Centre National de Référence des bactéries anaérobies et du botulisme, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, 184 rue du Faubourg Saint-Antoine, 75012 Paris France, UMR-S 1139 3PHM, Université Paris Cité, Paris, France.
Clostridioides difficile is a Gram-positive, spore-forming anaerobic enteropathogen responsible for a wide spectrum of clinical diseases ranging from mild diarrhoea to pseudomembranous colitis. It is the first cause of healthcare-associated diarrhoeas, but community-associated Clostridioides difficile infections (CDI) are increasingly reported in patients without the common risk factors (age > 65 years, previous antibiotic treatment). The main C.
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Donor-derived fecal micrrasobiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo.
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View Article and Find Full Text PDFGut Microbes
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Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology.
View Article and Find Full Text PDFAppl Environ Microbiol
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Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
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