title: Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis.
abstract: OBJECTIVE
  An estimated 20-30% of patients with primary Clostridium difficile infection (CDI) develop recurrent CDI (rCDI) within 2 weeks of completion of therapy. While the actual mechanism of recurrence remains unknown, a variety of risk factors have been suggested and studied. The aim of this systematic review and meta-analysis was to evaluate current evidence on the risk factors for rCDI.
  
  
  METHODS
  We searched MEDLINE and 5 other databases for subject headings and text related to rCDI. All studies investigating risk factors of rCDI in a multivariate model were eligible. Information on study design, patient population, and assessed risk factors were collected. Data were combined using a random-effects model and pooled relative risk ratios (RRs) were calculated.
  
  
  RESULTS
  A total of 33 studies (n=18,530) met the inclusion criteria. The most frequent independent risk factors associated with rCDI were age≥65 years (risk ratio [RR], 1.63; 95% confidence interval [CI], 1.24-2.14; P=.0005), additional antibiotics during follow-up (RR, 1.76; 95% CI, 1.52-2.05; P<.00001), use of proton-pump inhibitors (PPIs) (RR, 1.58; 95% CI, 1.13-2.21; P=.008), and renal insufficiency (RR, 1.59; 95% CI, 1.14-2.23; P=.007). The risk was also greater in patients previously on fluoroquinolones (RR, 1.42; 95% CI, 1.28-1.57; P<.00001).
  
  
  CONCLUSIONS
  Multiple risk factors are associated with the development of rCDI. Identification of modifiable risk factors and judicious use of antibiotics and PPI can play an important role in the prevention of rCDI.
authors.affiliation: 1Medicine Institute Center for Value Based Care Research,Cleveland Clinic,Cleveland,Ohio.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: 3Department of Medicine,Division of Infectious Diseases,Case Western Reserve University,Cleveland,Ohio.
authors.forename: Vinay
authors.initials: V
authors.lastname: Pasupuleti
authors.affiliation: 3Department of Medicine,Division of Infectious Diseases,Case Western Reserve University,Cleveland,Ohio.
authors.forename: Priyaleela
authors.initials: P
authors.lastname: Thota
authors.affiliation: 4Department of Gastroenterology,University of Kansas Medical Center,Kansas City,Kansas.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Pant
authors.affiliation: 5Department of Internal Medicine,Geisinger Medical Center,Danville,Pennsylvania.
authors.forename: David D K
authors.initials: DD
authors.lastname: Rolston
authors.affiliation: 6Postgraduate and Medical Schools,Universidad Peruana de Ciencias Aplicadas (UPC),Lima,Peru.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Hernandez
authors.affiliation: 3Department of Medicine,Division of Infectious Diseases,Case Western Reserve University,Cleveland,Ohio.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Donskey
authors.affiliation: 2Department of Infectious Diseases,Medicine Institute,Cleveland Clinic,Cleveland,Ohio.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Fraser
mesh_terms: D016360:Clostridioides difficile; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D012008:Recurrence; D012307:Risk Factors