Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea

Lancet. 1998 Feb 28;351(9103):633-6. doi: 10.1016/S0140-6736(97)08062-8.


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.

Method: 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.

Findings: 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.

Interpretation: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Carrier State
  • Clostridioides difficile / growth & development*
  • Clostridioides difficile / isolation & purification
  • Cross Infection / microbiology
  • Cross Infection / transmission
  • Diarrhea / microbiology*
  • Enterocolitis, Pseudomembranous / microbiology*
  • Enterocolitis, Pseudomembranous / transmission
  • Feces / microbiology*
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Risk Factors


  • Anti-Bacterial Agents