title: Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea.
abstract: BACKGROUND
  Little is known about whether patients who develop Clostridium-difficile-associated diarrhoea (CDAD) are culture-positive or culture-negative before illness. The most important risk factor is antibiotic exposure. We aimed to find out whether patients identified as primary symptom-free C difficile carriers are at higher risk of developing CDAD than patients who are culture-negative.
  
  
  METHODS
  We reviewed four longitudinal studies in which 810 patients admitted to hospital were followed up by prospective rectal-swab culture. At least two consecutive weekly cultures were obtained. We calculated the difference in risk of CDAD between colonised and non-colonised patients in each study and combined the results of the four studies in a random-effects model.
  
  
  RESULTS
  Of 618 non-colonised patients (mean follow-up 1.7 weeks [SD 1.3]), 22 (3.6%) developed CDAD, whereas only two (1.0%) of 192 primary symptom-free carriers (1.5 [1.5]) developed CDAD (pooled risk difference -2.3% [95% CI 0.3-4.3], p=0.021). Of patients who received antibiotics, the risk difference was increased: 22 (4.5%) of 491 non-colonised patients compared with two (1.1%) of 176 colonised patients developed CDAD (-3.2% [0.4-6.0], p=0.024). Of the primary symptom-free C difficile carriers, 95 were colonised with toxigenic strains, 76 with non-toxigenic strains, 12 with both toxigenic and non-toxigenic strains (non-concurrently), and nine with strains of undetermined toxigenicity. Nine of the 12 toxogenic strains of C difficile isolates that cause CDAD were also recovered from stools of symptom-free patients.
  
  
  CONCLUSIONS
  Primary symptomless C difficile colonisation is associated with a decreased risk of CDAD. Although the mechanism is unknown, risk reduction is found in colonisation with non-toxigenic and toxigenic strains.
authors.affiliation: Department of Medicine, Veterans Affairs Chicago Healthcare System, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Shim
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: M H
authors.initials: MH
authors.lastname: Samore
authors.forename: D Z
authors.initials: DZ
authors.lastname: Bliss
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002353:Carrier State; D016360:Clostridioides difficile / Q000254:growth & development* / Q000302:isolation & purification; D003428:Cross Infection / Q000382:microbiology / Q000635:transmission; D003967:Diarrhea / Q000382:microbiology*; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology* / Q000635:transmission; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents