A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO)

Barker, Anna; Duster, Megan; Valentine, Susan; Hess, Timothy; Archbald-Pannone, Laurie; Guerrant, Richard L.; Safdar, Nasia

doi:10.1093/jac/dkx254

Cited by 73 publications

(51 citation statements)

References 18 publications

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“…Among the 38 potentially relevant studies, 28 were further excluded because they were laboratory studies (n = 2), without the use of probiotics (n = 3), included non‐CDAD patients (n = 7), or with insufficient data (n = 16). Finally, 10 trials, including 11 analyses and 4 692 participants and containing nine separate different probiotic interventions, were identified and included. The flowchart of literature search is shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we further performed a network meta‐analysis based on different antibiotic types. Three RCTs compared the duration of diarrhea between the two groups. The overall efficacy of the probiotic intervention arm was −0.81 (SMD; 95% CI: −2.06‐0.44), with no significant differences in the results.…”

Section: Resultsmentioning

confidence: 99%

“…Among the 38 potentially relevant studies, 28 were further excluded because they were laboratory studies (n = 2), without the use of probiotics (n = 3), included non-CDAD patients (n = 7), or with insufficient data (n = 16). Finally, 10 trials, [24][25][26][27][28][29][30][31][32][33] Table 1. Assessment of the risk of bias is presented in Figure S1,…”

Section: Study Characteristics and Methodological Qualitymentioning

confidence: 99%

“…The efficacy of probiotics on the incidence of CDAD in all 10 included RCTs, [24][25][26][27][28][29][30][31][32][33] and each kind of probiotic intervention was estimated in at least one RCT. The direct comparison results showed that the occurrence of CDAD was reduced after probiotic intervention compared with the control group (OR 0.33, 95% CI 0.17-0.61) with moderate heterogeneity (P = 0.060, I 2 = 43.5%).…”

Section: Primary Outcome: Incidence Rate Of Cdadmentioning

confidence: 99%

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Which probiotic has the best effect on preventing Clostridium difficile‐associated diarrhea? A systematic review and network meta‐analysis

Yang

Xia

et al. 2020

J of Digest Diseases

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Objective Clostridium difficile‐associated diarrhea (CDAD) accounts for up to 25% of patients with antibiotic‐associated diarrhea (AAD). We aimed to determine which probiotic is most effective in preventing CDAD using a network meta‐analysis. Methods Studies were identified by searching PubMed, EMBASE and the Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the efficacy of probiotic interventions for CDAD. Primary outcomes were the incidence rates of AAD and CDAD, and secondary outcomes were the duration of diarrhea and the time until onset of diarrhea. The PROSPERO registered number of this study is CRD42018106115. Results Ten RCTs including 11 analyses and including 4 692 patients were identified. Compared with the control group, probiotic intervention reduced the incidence rates of CDAD (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.17‐0.61) and AAD (OR 0.39, 95% CI 0.23‐0.66). Similar results were observed regarding the duration of diarrhea and the time until onset of diarrhea. Meta‐regression analysis showed a correlation between the type of probiotic used and the incidence of CDAD and AAD. All nine kinds of probiotic interventions were statistically more effective than the placebo, with Lactobacillus casei ranking as the best intervention (OR 0.19, 95% credible interval [CrI] 0.06‐0.63) for decreasing the incidence rate of CDAD. L. casei also ranked the highest in reducing the incidence rate of AAD (OR 0.32, 95% CrI 0.14‐0.74). Conclusion Lactobacilli strains, especially L. casei, have a good effect on the prevention of CDAD and AAD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Study Characteristics and Methodological Qualitymentioning

confidence: 99%

Section: Primary Outcome: Incidence Rate Of Cdadmentioning

confidence: 99%

See 2 more Smart Citations

Which probiotic has the best effect on preventing Clostridium difficile‐associated diarrhea? A systematic review and network meta‐analysis

Yang

Xia

et al. 2020

J of Digest Diseases

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“…These findings could appear counterintuitive as Lactobacillus species are frequently included in probiotic formulations for preventing CDI relapses, while Faecalibacterium prausnitzii has been used in a bacteriotherapy trial aiming to eradicate CDI in two patients [16][17][18][19][20] . As these microbes are often administered in combination 24 , the exact contribution of each of its species to the treatment or prevention of CDI remains undetermined and requires further studies.…”

Section: Discussionmentioning

confidence: 99%

Alcohol pretreatment of stools effect on culturomics

Afouda

Hocquart

Pham

et al. 2020

Sci Rep

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Recent studies have used ethanol stool disinfection as a mean of promoting valuable species' cultivation in bacteriotherapy trials for Clostridium difficile infections (CDI) treatment with a particular focus on sporulating bacteria. Moreover, the culturomic approach has considerably enriched the repertoire of cultivable organisms in the human gut in recent years. This study aimed to apply this culturomic approach on fecal donor samples treated with ethanol disinfection to evidence potential beneficial microbes that could be used in bacteriotherapy trials for the treatment of CDI. Thereby, a total of 254 bacterial species were identified, 9 of which were novel. Of these, 242 have never been included in clinical trials for the treatment of CDIs, representing potential new candidates for bacteriotherapy trials. While non-sporulating species were nevertheless more affected by the ethanol pretreatment than sporulating species, the ethanol disinfection technique did not specifically select bacteria able to sporulate, as suggested by previous studies. Furthermore, some bacteria previously considered as potential candidates for bacteriotherapy have been lost after ethanol treatment. This study, while enriching the bacterial repertoire of the human intestine, would nevertheless require determining the exact contribution of each of species composing the bacterial consortia intended to be administered for CDI treatment. Clostridium difficile infection (CDI) represents a public health problem worldwide as it is associated with significant morbidity and mortality 1-4. This infection, due to the establishment of toxigenic C. difficile in the human digestive tract is a consequence of intestinal microbiota imbalance 5 due to antibiotic intake. Until recently, the administration of antimicrobial agents was the treatment of choice for this type of infection and therefore exposed patients to the risk of recurrence of CDI 6. The modification of the gut microbiota during antibiotic treatment induces an increase in the production of succinate. Indeed, Clostridium difficile can use this succinate produced by converting it into butyrate, thus promoting its colonization of the host's intestine 7. Otherwise, alternative treatments to antibiotics are increasingly being used, such as the use of monoclonal antibodies against toxins produced by Clostridium difficile, vaccination against Clostridium difficile infection, transplantation of non-toxic strains of Clostridium difficile, but also the use of transplants of healthy faecal microbiota from healthy subjects 8-10. Fecal microbiota transplantation for the treatment of CDI recurrence has been shown to be effective in recent years 11-14. However, its non-standardization and its unattractive character 15 have led to the emergence of studies on bacteriotherapy, which consists of using non-toxic, bacterial cocktails, sporulating or not, isolated from the feces of fecal transplant donors to treat or prevent CDI recurrence 9,16-18. Several mixtures of bacterial strains (previously known or new sp...

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Clinical efficacy of probiotics in prevention of infectious diseases among hospitalized patients in ICU and non‐ICU wards in clinical randomized trials: A systematic review

Darbandi

Banar

Koupaei

et al. 2023

Health Science Reports

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Background and AimsThe present study aimed to review probiotics' clinical efficacy in preventing infectious diseases among hospitalized patients in ICU and non‐ICU wards.MethodsA search of Medline, EMBASE, The Cochrane Library, Science Direct, Open Grey, and Google Scholar was conducted for eligible publications from 2002 to 2020 following the requirements outlined in the PRISMA guideline. The search strategy was based on the combination of the following terms: “probiotics,” “prebiotics,” “synbiotics,” and “cross‐infection.” The logical operators “AND” (or the equivalent operator for the databases) and “OR” (e.g., probiotics OR prebiotics OR synbiotics) were used.ResultsThe results indicated that the probiotic consumption caused a significant reduction in antibiotic‐associated diarrhea (AAD) and Clostridioides difficile infection (CDI) in 2/8 randomized clinical trials (RCTs) investigating AAD/CDI. Also, 5/12 clinical trials highlighted the considerable effects of probiotics on the reduction or prevention of ventilator associated pneumoniae (VAP), so the mean prevalence of VAP was lower in the probiotic group than in the placebo group. The total rate of nosocomial infections among preterm infants was nonsignificantly higher in the probiotic group compared to the control group.ConclusionThis systematic review shows that the administration of probiotics has moderate preventive or mitigating effects on the occurrence of VAP in ICU patients, CDI, AAD, and nosocomial infections among children. Consequently, applying antibiotics along with the proper probiotic species can be advantageous.

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A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO)

Abstract: Probiotics are a promising adjunct therapy for treatment of an initial CDI and should be further explored in a larger randomized controlled trial.

Cited by 73 publications

References 18 publications

Which probiotic has the best effect on preventing Clostridium difficile‐associated diarrhea? A systematic review and network meta‐analysis

Which probiotic has the best effect on preventing Clostridium difficile‐associated diarrhea? A systematic review and network meta‐analysis

Alcohol pretreatment of stools effect on culturomics

Clinical efficacy of probiotics in prevention of infectious diseases among hospitalized patients in ICU and non‐ICU wards in clinical randomized trials: A systematic review

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