title: The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI.
  
  
  METHODS
  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.
  
  
  METHODS
  Two authors independently reviewed the studies for eligibility.
  
  
  METHODS
  Data about studies characteristics, adjusted effect estimates and quality were extracted.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia. tleyjeh.imad@mayo.edu
authors.forename: Imad M
authors.initials: IM
authors.lastname: Tleyjeh
authors.forename: Aref Bin
authors.initials: AB
authors.lastname: Abdulhak
authors.forename: Aref A Bin
authors.initials: AA
authors.lastname: Abdulhak
authors.forename: Muhammad
authors.initials: M
authors.lastname: Riaz
authors.forename: Musa A
authors.initials: MA
authors.lastname: Garbati
authors.forename: Mohamad
authors.initials: M
authors.lastname: Al-Tannir
authors.forename: Faisal A
authors.initials: FA
authors.lastname: Alasmari
authors.forename: Mushabab
authors.initials: M
authors.lastname: Alghamdi
authors.forename: Abdur Rahman
authors.initials: AR
authors.lastname: Khan
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Sutton
authors.forename: Larry M
authors.initials: LM
authors.lastname: Baddour
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D016360:Clostridioides difficile / Q000187:drug effects / Q000254:growth & development; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006760:Hospitalization; D006801:Humans; D008297:Male; D011970:Receptors, Histamine H2 / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2