Randomised clinical trial: a 12‐strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections

Abstract

SummaryBackgroundA defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT).AimsTo compare the efficacy of a 12‐strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open‐label 3‐arm randomised controlled trial.MethodsWe screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory‐confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre‐treated with vancomycin for 7‐14 days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14 days. The vancomycin group was treated for 14 days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90 days. A secondary outcome was 180‐day all‐cause mortality.ResultsParticipants in the FMT group (n = 34) were cured more often than participants receiving vancomycin (n = 31), 76% vs 45% (OR 3.9 (1.4‐11.4), P < 0.01) or rectal bacteriotherapy (n = 31), 76% vs 52% (OR 3.0 (1.1‐8.8), P = 0.04). Rectal bacteriotherapy and vancomycin performed similarly (P = 0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04‐1.12), P = 0.07.ConclusionsRectal bacteriotherapy appears as effective as vancomycin but less effective than 1‐3 FMTs. FMT by enema with 1‐3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality.

Transplante de microbiota fecal para o tratamento da infecção por Clostridioides difficile: revisão sistemática e metanálise

“…Na avaliação crítica dos estudos (validade interna), em relação ao sigilo de alocação, oito artigos foram classificados como Categoria A (30)(31)(32)(33)35,37,40,42) , pois descrevem adequadamente o processo de alocação; quatro como Categoria B (34,38,39,41) por mencionarem o processo de randomização dos participantes; e dois artigos alocaram os participantes de forma inadequada, recebendo, portanto, Categoria C (36,42) . Nenhum estudo foi identificado como Categoria D.…”

“…A principal via de administração relatada nos estudos foi o trato gastrointestinal inferior guiada por colonoscopia. (32,34,36,38,40,43) Outras vias de administração adotadas foram a retal (enema) (31,33,37,42) , cápsulas orais (35) , nasogástrica (38) , nasoduodenal (41) , nasojujenal e endoscópica (40) . Entre as vias testadas não houve diferenças significativas para o desfecho resolução clínica da diarreia.…”

Problematik Infeksi Clostridium difficile

“…A multidisciplinary antibiotic management program to limit inappropriate antibiotic use could lead to a significant reduction in nosocomial infections caused by C. difficile. 39,40 The first steps in treating patients with CDI include discontinuing the offending agent such as antimicrobials, if possible, and providing appropriate supportive care with hydration and electrolyte replacement as needed. Anti-diarrhea medications should be avoided as they can obscure symptoms and trigger toxic megacolon.…”

“…Therefore, local guidelines, based on the local epidemiology of CDI, should be developed in each country to resolve the debate, as most treatment guidelines are formulated in developed countries, as listed in Table 2. 40,41 between the 2 treatment groups. 42,43 The role of metronidazole in patients with first-time events and non-severe disease remains controversial.…”

ACaenorhabditis elegansbased system for high-throughput functional phenotyping of human gut microbiota

“…This gap in understanding highlights the need for a defined bacterial therapy that can provide a clear understanding of biotherapeutic mechanisms, enabling precise dosing. The random selection of bacteria in clinical trials has not always yielded the expected therapeutic efficacy, raising questions about the best approach to biotherapeutic interventions 18,19 . Even though multiple studies address colonization in vitro , one of the significant challenges in this field is replicating in-vitro inhibition data in in-vivo environments.…”