Dramatic reduction in Clostridium difficile ribotype 027-associated mortality with early fecal transplantation by the nasogastric route: a preliminary report
Authors: D Raoult
P Brouqui
A Stein
M Million
P Parola
J-C Lagier
M Delord
Journal: European Journal of Clinical Microbiology & Infectious Diseases (2015)
Discipline: MICROBIOLOGY
Keywords: Clostridium difficile; ribotype 027; diarrhea; elderly patients; mortality rate
Affiliations: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, 13005, Marseille, France.

Abstract:  Clostridium difficile ribotype 027 (CD027)-associated diarrhea preferentially affects elderly patients and causes a high mortality rate. Fecal microbiota transplantation has become an alternative treatment for recurrent C. difficile infections. An outbreak of CD027 infections has occurred in Marseille since March 2013. From March to November 2013, we treated patients using only antibiotics or fecal microbiota transplantation after at least three relapses. Beginning in November 2013, we performed early transplantation using a nasogastric tube during the first week of infection, in combination with antibiotic treatment. Sixty-one patients with a mean age of 84 years were hospitalized, including 42 patients treated only with antibiotics, three with tardive transplantation, and 16 with early transplantation. The patients were comparable in clinical involvement. The global mortality rate was 3/16 (18.75 %) among the patients treated by early transplantation and 29/45 (64.4 %) among the patients only treated by antibiotics or by tardive transplantation (p &lt; 0.01). Among these 45 patients, 23 (51 %) died at day 31, including 17 who died at day 7. Early fecal transplantation was associated with a significantly reduced mortality rate, with only one patient dead at day 31 (6.25 %). In a Cox model, early transplantation was the only independent predictor of survival (hazard ratio 0.18, 95 % confidence interval 0.05-0.61, p = 0.006). Six of the 16 patients (37.5 %) needed a second transplantation before symptom resolution. Early fecal microbiota transplantation in combination with antibiotics should be the first-line treatment for CD027 infections. 

Retracted: No

PubPeer comments:
 This article describes a prospective study using experimental treatment (fecal transplantation) : *We show here the preliminary results of a before and after open prospective study comparing the mortality of patients treated conventionally by antibiotics with patients treated with early transplantation, via the nasogastric route, in addition to the usual antibiotics.* From March 2013 to November 2013, participants to this prospective study used a classic antibiotic regimen. Then in December 2012, the prospective study used an experimental treatment. It raises serious questions related to ethic approvals. Authors mentioned to have applied the ethical rules stated by the French Health Authority. But the reference they mentionned recommend to perform a clinical trial when using a fecal transplantation. Indeed, Fecal transplantation must be considered as an experimental medicine. In this case, the clinical trial must obtain the approval of the Health Authority (ANSM) and an ethics committee called Comitu00e9 de Protection des Personnes. The clinical trials must also obtain an EudraCT number and be registered in the European Clinical Registry. These authorisation must be obtained before the recruitment of participants. They are the recommandations of the reference the author mentions. However, this is not what the authors reported in the article. Authors mentioned to have complied with the French Legislation on the research involving humans. But the authors did not report: - a CPP approval number - an ANSM approval number - an EudraCT number. Furthermore, this clinical trials using an experimental treatment is not mentioned on the European Clinical Trial Registry (EU-CTR). Reader could be concerned by the lack of ethical approval for this prospective study in humans using an experimental medicine. It is also a serious breach to the Declaration of Helsinki. Indeed, article 23 requires to obtain an ethic approval and all authorisations in line with the local regulations. If not, the article can not be considered for publication. Editor Policy of the journal is aligned with this requirement. It is quite surprizing that the article was peer reviewed as the authors were not able to provide ethical approvals from a CPP and the ANSM prior to start the study. Editor should consider this ethical concern and review the ethical process in order to ensure that the study obtained a CPP approval and an ANSM approval before to start. If not, the article must be considered for a retraction. ,