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Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.
Anaerobe 2019; :102098A

Abstract

Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.

Authors+Show Affiliations

Tufts University School of Medicine, Boston, MA, USA; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: Sarah.Madoff@tufts.edu.Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31493500

Citation

Madoff, Sarah E., et al. "Prevention of Recurrent Clostridioides Difficile Infection: a Systematic Review of Randomized Controlled Trials." Anaerobe, 2019, p. 102098.
Madoff SE, Urquiaga M, Alonso CD, et al. Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials. Anaerobe. 2019.
Madoff, S. E., Urquiaga, M., Alonso, C. D., & Kelly, C. P. (2019). Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials. Anaerobe, p. 102098. doi:10.1016/j.anaerobe.2019.102098.
Madoff SE, et al. Prevention of Recurrent Clostridioides Difficile Infection: a Systematic Review of Randomized Controlled Trials. Anaerobe. 2019 Sep 4;102098. PubMed PMID: 31493500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials. AU - Madoff,Sarah E, AU - Urquiaga,Mariana, AU - Alonso,Carolyn D, AU - Kelly,Ciarán P, Y1 - 2019/09/04/ PY - 2019/02/04/received PY - 2019/08/28/revised PY - 2019/09/03/accepted PY - 2019/9/8/pubmed PY - 2019/9/8/medline PY - 2019/9/8/entrez KW - Bezlotoxumab KW - Fecal microbiota transplant KW - Fidaxomicin KW - Probiotic KW - Recurrent Clostridioides difficile infection KW - Vancomycin SP - 102098 EP - 102098 JF - Anaerobe JO - Anaerobe N2 - Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next. SN - 1095-8274 UR - https://www.unboundmedicine.com/medline/citation/31493500/Prevention_of_recurrent_Clostridioides_difficile_infection:_A_systematic_review_of_randomized_controlled_trials L2 - https://linkinghub.elsevier.com/retrieve/pii/S1075-9964(19)30158-1 DB - PRIME DP - Unbound Medicine ER -