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Background: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT)., Aims: To 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., Methods: We 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., Results: Participants 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., Conclusions: Rectal 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., (© 2021 John Wiley & Sons Ltd.)

Clostridium difficile infection is one of the most common nosocomial infections. Among other alternatives to standard treatment with vancomycin for recurrent infection are faecal microbiota transplantation and rectal bacteriotherapy with a fixed mixture of intestinal bacterial strains isolated from faeces of healthy persons to mimic a theoretical normal microflora. Developed by Dr. Tvede and Dr. Rask-Madsen, the latter method has been in use for selected patients during the last 25 years in Denmark. In this study we reviewed the medical records of patients treated with rectal bacteriotherapy for relapsing C. difficile in Denmark, 2000-2012. The primary end point was recurrent diarrhoea within 30 days after treatment. A total of 55 patients were included in this case series. Thirty-five patients (64%) had no recurrence within 30 days of bacteriotherapy. Patients with recurrence tended to be older (75.8 years vs. 61.3 years; p 0.26), and more often have preexisting gastrointestinal illness and longer duration of time from the first CDI to bacteriotherapy (221.6 days vs. 175.3 days; p 0.18). Treatment success was 80% in the subgroup of patients with no known gastrointestinal illness and first C. difficile episode less than 6 months before bacteriotherapy. The most common adverse events were abdominal pain (10.9%) and worsening diarrhoea (4.3%). One patient was hospitalized 10 days after treatment with appendicitis, fever, and Escherichia coli bacteremia. The results from this study indicate that rectal bacteriotherapy is a viable alternative to faecal microbiota transplantation in patients with relapsing C. difficile-associated diarrhoea., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A total of 65 toxigenic Clostridium difficile strains isolated from patients with antibiotic-associated diarrhea were tested for susceptibility to avilamycin, flavomycin, monensin, and salinomycin. Except for flavomycin the substances showed in vitro efficacy comparable to reports of the currently most commonly used drugs for treatment of C. difficile. This indicates that these old compounds may be useful for the treatment of C. difficile infections in man and perhaps for other bacterial causes of diarrhea., (© Mary Ann Liebert, Inc.)

The incidence of Clostridium difficile-associated infections is increasing, but it remains to be defined whether any change in the seroprevalence of C. difficile has also occurred. In a population-based study of the general adult population, 734 subjects, aged 15-69 years, were examined on two occasions 8 years apart (1990 and 1998) for the presence of antibodies against C. difficile in serum. The overall seroprevalence of C. difficile increased significantly from 19% in 1990 to 27% in 1998 (P<0.0001). The seroprevalence increased with increasing age in both 1990 and 1998, but the increase was about four times higher in 1998 than in 1990. In conclusion, the observed increase in seroprevalence suggests a higher exposure to C. difficile in the general Danish adult population.

Objective: To conduct a survey of the methods used in clinical microbiology laboratories in Europe to diagnose infection with Clostridium difficile., Methods: A questionnaire was devised and sent to a co-ordinating member of the Study Group in each of eight European countries. This co-ordinator was in charge of forwarding the questionnaire to hospital laboratories arbitrarily selected. The number of laboratories in each country was determined on the basis of one laboratory for 10,000 beds of hospitalization. This questionnaire covered different aspects pertaining to Clostridium difficile associated to diarrhea (CDAD) diagnosis such as circumstances of request, criteria used for undertaking C. difficile investigations, methods used for the diagnosis, etc., Results: A total of 212 questionnaires were completed and submitted for analysis: 87.7% of laboratories reported routinely performing C. difficile diagnostic tests. Methods used included toxin detection (93%), culture (55%), and glutamate dehydrogenase (GDH) detection (5.9%). Among the laboratories detecting toxins, different enzyme immunoassays (EIA) and cytotoxicity assays were used in 79% and 17.3% of cases, respectively. Among the different strategies reported, 4.8% were considered suboptimal for the diagnosis of C. difficile infections, but marked discrepancies could be observed between countries. The overall incidence (median) of CDAD was estimated at 1.1 for 1,000 patient admissions., Conclusion: The results of this study suggest marked discrepancies between laboratories and also between countries regarding the criteria by which C. difficile is investigated for, and the methods and the strategies that are used for the diagnosis of C. difficile. These discrepancies could be explained by the lack of clear guidelines for C. difficile diagnosis in each country, and by the importance that physicians attach to C. difficile. Precise guidelines for C. difficile diagnosis would be the first step to make possible accurate comparison of the incidence and the epidemiology of CDAD from one hospital to another or from one country to another.

Background: It has been hypothesized that Clostridium difficile and decreased colonic production of short-chain fatty acids (SCFAs) cause the development of antibiotic-associated diarrhoea. We therefore wanted to investigate the effects of an intensive and uniform antibiotic therapy on faecal SCFAs concentrations. C. difficile, and extent of diarrhoea., Methods: Fifteen liver-transplanted patients who received oral bowel flora suppression therapy (6.3 g cefuroxime, 0.6 g tobramycin, and 0.5 g nystatin three times daily) were studied for 12 days before and 12 days after discontinuation of therapy., Results: Thirteen of the 15 patients (87%) developed diarrhoea. Colonic fermentation was negligible in all patients, judged by very low levels of faecal SCFAs (< 10 mmol/l). Diarrhoea lessened as suppression therapy proceeded despite continuous low levels of SCFAs. Initial stool frequency of 4.1 +/- 0.6 and viscosity of 2.5 +/- 0.2 per day (on a scale of 1-3; mean +/- SE) decreased to 2.2 +/- 0.5 (p = 0.0009) and 1.6 +/- 0.2 (p = 0.003) per day, respectively, just before cessation of suppression therapy. Both SCFAs and stool habits normalized within days after discontinuation of antibiotics. Only a few samples from 2 patients were culture-positive for C. difficile during therapy, whereas 9 of the 15 patients (60%) became culture-positive (6 cytotoxin-positive) after cessation of suppression therapy at a time when none had diarrhoea., Conclusions: Intensive treatment with antibiotics directed against the colonic flora resulted in diarrhoea in the vast majority of patients, but the diarrhoea was self-limiting despite continual antibiotic treatment and very low faecal concentrations of SCFAs. C. difficile was not associated with antibiotic-associated diarrhoea but was a common finding after treatment with antibiotics was stopped at the time when diarrhoea had ceased.

A polymerase chain reaction (PCR) for demonstration of gene fragments of Clostridium difficile was established. One hundred and sixty-eight clinical isolates of C. difficile from three population groups were tested for production of cytotoxins by McCoy cell line assay (MCA) and for fragments of toxin A and B genes by PCR. The fragments for PCR amplification were at the 5' end of the toxin genes, which was found to be specific for C. difficile. Full agreement between the PCR and MCA results was found with respect to toxicity. Fifty-eight of the 168 strains were cytotoxin positive. Isolates from 41 normal healthy children did not differ regarding cytotoxicity compared to isolates from hospitalized children. In adult hospitalized patients a much higher frequency of toxin-producing isolates was found. In two strains from two children, not of the same family, only the toxin A gene fragment was demonstrated, indicating that some strains of C. difficile only harbour the gene for enterotoxin. When two isolates from different periods of time were tested from 36 of the healthy children, a variation in cytotoxicity was found: in seven children strains changed from non-toxic to toxic and in four vice versa. This may be explained by a fluctuating colonization of toxic and non-toxic C. difficile strains, or it may indicate the need for examination of more than one strain from a positive faecal sample to demonstrate cytotoxicity.

A prospective, consecutive study of the aetiology of treatment-associated diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated with intensive chemotherapy. Clostridium difficile was isolated in 45% of the diarrhoea episodes, which makes this species the most important bacterial pathogen in the development of clinically significant diarrhoea in this group of immunocompromised patients.

To conduct a survey of the methods used in clinical microbiology laboratories in Europe to diagnose infection with Clostridium difficile. A questionnaire was devised and sent to a co-ordinating member of the Study Group in each of eight European countries. This co-ordinator was in charge of forwarding the questionnaire to hospital laboratories arbitrarily selected. The number of laboratories in each country was determined on the basis of one laboratory for 10 000 beds of hospitalization. This questionnaire covered different aspects pertaining to Clostridium difficile associated to diarrhea (CDAD) diagnosis such as circumstances of request, criteria used for undertaking C. difficile investigations, methods used for the diagnosis, etc. A total of 212 questionnaires were completed and submitted for analysis: 87.7% of laboratories reported routinely performing C. difficile diagnostic tests. Methods used included toxin detection (93%), culture (55%), and glutamate dehydrogenase (GDH) detection (5.9%). Among the laboratories detecting toxins, different enzyme immunoassays (EIA) and cytotoxicity assays were used in 79% and 17.3% of cases, respectively. Among the different strategies reported, 4.8% were considered suboptimal for the diagnosis of C. difficile infections, but marked discrepancies could be observed between countries. The overall incidence (median) of CDAD was estimated at 1.1 for 1000 patient admissions. The results of this study suggest marked discrepancies between laboratories and also between countries regarding the criteria by which C. difficile is investigated for, and the methods and the strategies that are used for the diagnosis of C. difficile. These discrepancies could be explained by the lack of clear guidelines for C. difficile diagnosis in each country, and by the importance that physicians attach to C. difficile. Precise guidelines for C. difficile diagnosis would be the first step to make possible accurate comparison of the incidence and the epidemiology of CDAD from one hospital to another or from one country to another. [ABSTRACT FROM AUTHOR]