The Association between Histamine 2 Receptor Antagonist Use and Clostridium difficile Infection: A Systematic Review and Meta-analysis

• Published in: PloS one Vol. 8; no. 3; p. e56498
• Main Authors: Tleyjeh, Imad M., Abdulhak, Aref A. Bin, Riaz, Muhammad, Garbati, Musa A., Al-Tannir, Mohamad, Alasmari, Faisal A., AlGhamdi, Mushabab, Khan, Abdur Rahman, Erwin, Patricia J., Sutton, Alex J., Baddour, Larry M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.03.2013; Public Library of Science (PLoS)
• Subjects: Acids; Adolescent; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Antibiotics; Bibliographic data bases; Biology; Case-Control Studies; Clostridioides difficile - drug effects; Clostridioides difficile - growth & development; Clostridium difficile; Clostridium infections; Data collection; Development and progression; Diarrhea; Drug therapy; Enterocolitis, Pseudomembranous - drug therapy; Enterocolitis, Pseudomembranous - microbiology; Epidemics; Epidemiology; Female; Heterogeneity; Histamine; Histamine H2 antagonists; Histamine H2 Antagonists - administration & dosage; Histamine H2 Antagonists - adverse effects; Hospitalization; Hospitals; Humans; Infections; Infectious diseases; Internal medicine; Literature reviews; Male; Medical ethics; Medical libraries; Medicine; Meta-analysis; Patient outcomes; Patients; Receptors, Histamine H2 - metabolism; Regression Analysis; Risk Factors; Studies; Subgroups; Subject heading schemes; Systematic review; Therapy; Saudi Arabia; Minnesota; Kansas City Missouri; United States > US; Riyadh Saudi Arabia; Missouri
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056498

Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Two authors independently reviewed the studies for eligibility. Data about studies characteristics, adjusted effect estimates and quality were extracted. Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22-1.7), I(2) = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15-1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics.