Administration of Spores of Nontoxigenic Clostridium difficile Strain M3 on account of Prevention of Recurrent C difficile Infection: A Randomized Clinical Trial.
JAMA. 2015 May 5;313(17):1719-1727
Authors: Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, Van Schooneveld TC, Pardi DS, Ramos A, Barron MA, Chen H, Villano S
Importance: Clostridium difficile is the greatest in quantity common cause of health care-associated pest in US hospitals. Recurrence occurs in 25% to 30% of patients.
Objective: To fix upon the safety, fecal colonization, recurrence defame, and optimal dosing schedule of nontoxigenic C difficile purify M3 (VP20621; NTCD-M3) for stoppage of recurrent C difficile infection (CDI).
Design, Setting, and Participants: Phase 2, randomized, double-leading nowhere, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed at the same time that having CDI (first episode or capital recurrence) and had successfully completed management with metronidazole, oral vancomycin, or the pair at 44 study centers in the United States, Canada, and Europe.
Interventions: Patients were randomly assigned to allow 1 of 4 treatments: oral dulcet formulation of NTCD-M3, 104 spores/d towards 7 days (n = 43), 107 spores/d as far as concerns 7 days (n = 44), or 107 spores/d in spite of 14 days (n = 42), or placebo against 14 days (n = 44).
Main Outcomes and Measures: The primeval outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory deputy outcomes included fecal colonization with NTCD-M3 from period of study drug through week 6 and CDI the having recourse from day 1 through week 6.
Results: Among 168 patients who started handling, 157 completed treatment. One or additional 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, particularly. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of entirely 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 107 spores/d and 63% with 104 spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (superiority ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 107 spores/d notwithstanding 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 by CDI who clinically recovered following usage with metronidazole or vancomycin, oral giving of spores of NTCD-M3 was well tolerated and appeared to subsist safe. Nontoxigenic C difficile strain M3 colonized the gastrointestinal portion and significantly reduced CDI recurrence.
Trial Registration: clinicaltrials.gov Identifier: NCT01259726.
PMID: 25942722 [PubMed – to the degree that supplied by publisher]
Sunday to catch the AT&T Pebble Beach National Pro-Am, earning his 40th course of conduct PGA title.