Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial
- PMID: 25942722
- DOI: 10.1001/jama.2015.3725
Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial
Abstract
Importance: Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients.
Objective: To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI).
Design, setting, and participants: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe.
Interventions: Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44).
Main outcomes and measures: The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6.
Results: Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001).
Conclusions and relevance: Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence.
Trial registration: clinicaltrials.gov Identifier: NCT01259726.
Comment in
-
Infection. Bacteriotherapy for recurrent C. difficile infection--spores to the rescue?Nat Rev Gastroenterol Hepatol. 2015 Jun;12(6):312. doi: 10.1038/nrgastro.2015.88. Epub 2015 May 19. Nat Rev Gastroenterol Hepatol. 2015. PMID: 25986301 No abstract available.
-
Non-toxigenic Clostridium difficile to prevent recurrent C. difficile infection.Evid Based Med. 2016 Apr;21(2):67. doi: 10.1136/ebmed-2015-110234. Epub 2016 Jan 13. Evid Based Med. 2016. PMID: 26763618 No abstract available.
Similar articles
-
Non-toxigenic Clostridioides (Formerly Clostridium) difficile for Prevention of C. difficile Infection: From Bench to Bedside Back to Bench and Back to Bedside.Front Microbiol. 2018 Jul 26;9:1700. doi: 10.3389/fmicb.2018.01700. eCollection 2018. Front Microbiol. 2018. PMID: 30093897 Free PMC article. Review.
-
Evaluation of an oral suspension of VP20621, spores of nontoxigenic Clostridium difficile strain M3, in healthy subjects.Antimicrob Agents Chemother. 2012 Oct;56(10):5224-9. doi: 10.1128/AAC.00913-12. Epub 2012 Jul 30. Antimicrob Agents Chemother. 2012. PMID: 22850511 Free PMC article. Clinical Trial.
-
Effective Colonization by Nontoxigenic Clostridioides difficile REA Strain M3 (NTCD-M3) Spores following Treatment with Either Fidaxomicin or Vancomycin.Microbiol Spectr. 2023 Mar 28;11(2):e0051723. doi: 10.1128/spectrum.00517-23. Online ahead of print. Microbiol Spectr. 2023. PMID: 36975811 Free PMC article.
-
Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. JAMA. 2014. PMID: 25322359 Clinical Trial.
-
Tigecycline for the treatment of severe Clostridium difficile infection.Ann Pharmacother. 2011 Jul;45(7-8):1005-10. doi: 10.1345/aph.1Q080. Epub 2011 Jul 5. Ann Pharmacother. 2011. PMID: 21730279 Review.
Cited by
-
An assessment of the future impact of alternative technologies on antibiotics markets.J Pharm Policy Pract. 2016 Oct 26;9:34. doi: 10.1186/s40545-016-0085-3. eCollection 2016. J Pharm Policy Pract. 2016. PMID: 27800166 Free PMC article.
-
Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.Inflamm Bowel Dis. 2016 Jul;22(7):1744-54. doi: 10.1097/MIB.0000000000000793. Inflamm Bowel Dis. 2016. PMID: 27120571 Free PMC article. Review.
-
Experience and Outcomes at a Specialized Clostridium difficile Clinical Practice.Mayo Clin Proc Innov Qual Outcomes. 2017 May 19;1(1):49-56. doi: 10.1016/j.mayocpiqo.2017.05.002. eCollection 2017 Jul. Mayo Clin Proc Innov Qual Outcomes. 2017. PMID: 30225401 Free PMC article.
-
Host Immune Responses to Clostridioides difficile: Toxins and Beyond.Front Microbiol. 2021 Dec 21;12:804949. doi: 10.3389/fmicb.2021.804949. eCollection 2021. Front Microbiol. 2021. PMID: 34992590 Free PMC article. Review.
-
Modeling Host-Microbiome Interactions in Caenorhabditis elegans.J Nematol. 2017 Dec;49(4):348-356. J Nematol. 2017. PMID: 29353922 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical