Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis.

Content Provider	Europe PMC
Author	Trifan, Anca Stanciu, Carol Girleanu, Irina Stoica, Oana Cristina Singeap, Ana Maria Maxim, Roxana Chiriac, Stefan Andrei Ciobica, Alin Boiculese, Lucian
Copyright Year	2017
Abstract	AIMTo perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI).METHODSWe conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS).RESULTSFifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002).CONCLUSIONThis meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
ISSN	10079327
Volume Number	23
PubMed Central reference number	PMC5643276
Issue Number	35
PubMed reference number	29085200
Journal	World Journal of Gastroenterology [World J. Gastroenterol]
e-ISSN	22192840
DOI	10.3748/wjg.v23.i35.6500
Language	English
Publisher	Baishideng Publishing Group Inc
Publisher Date	2017-09-01
Access Restriction	Open
Rights License	This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Subject Keyword	Proton pump inhibitors Clostridium difficile infection Risk Systematic review Meta-analysis
Content Type	Text
Resource Type	Article
Subject	Gastroenterology