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.

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.

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 noncolonised 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 nontoxigenic 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.

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.