Beinortas, T, Barr, NE, Wilcox, MH orcid.org/0000-0002-4565-2868 et al. (1 more author) (2018) Comparative efficacy of treatments for Clostridioides difficile infection: a systematic review and network meta-analysis. Lancet Infectious Diseases, 18 (9). pp. 1035-1044. ISSN 1473-3099
Abstract
Background: Several new treatments for Clostridium difficile infections have been investigated. We aimed to compare and rank treatments for non-multiply recurrent infections with C difficile in adults.
Methods: We did a random effects network meta-analysis within a frequentist setting to obtain direct and indirect comparisons of trials. We searched MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for published and unpublished trials from the creation of these databases until June 30, 2017. We included randomised controlled trials of treatments for non-multiply recurrent infections with confirmed C difficile in adults (at least 18 years) that reported both primary cure and recurrence rates, and we used the Cochrane Risk of Bias tool to appraise trial methods. For our analysis, we extracted the total numbers of patients with primary cure and recurrence from published and unpublished reports. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhoea minus the number with recurrence or death.
Findings: Of 23 004 studies screened, 24 trials, which comprised 5361 patients and 13 different treatments, were included in the analysis. The overall quality of evidence was rated as moderate to low. For sustained symptomatic cure, fidaxomicin (odds ratio 0·67, 95% CI 0·55–0·82) and teicoplanin (0·37, 0·14–0·94) were significantly better than vancomycin. Teicoplanin (0·27, 0·10–0·70), ridinilazole (0·41, 0·19–0·88), fidaxomicin (0·49, 0·35–0·68), surotomycin (0·66, 0·45–0·97), and vancomycin (0·73, 0·56–0·95) were better than metronidazole. Bacitracin was inferior to teicoplanin (0·22, 0·06–0·77) and fidaxomicin (0·40, 0·17–0·94), and tolevamer was inferior to all drugs except for LFF571 (0·50, 0·18–1·39) and bacitracin (0·67, 0·28–1·58). Global heterogeneity of the entire network was low (Cochran's Q=15·70; p=0·47).
Interpretation: Among the treatments for non-multiply recurrent infections by C difficile, the highest quality evidence indicates that fidaxomicin provides a sustained symptomatic cure most frequently. Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C difficile.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Elsevier Ltd. This is an author produced version of a paper published in The Lancet Infectious Diseases. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | clostridium difficile; network; meta-analysis; teicoplanin; ridinidazole; fidaxomicin; vancomycin; suratomycin; CDI; sustained cure |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Molecular Gastroenterology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Jul 2018 10:13 |
Last Modified: | 17 Jan 2019 01:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/S1473-3099(18)30285-8 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:133456 |