We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C difficile diarrhoea, influences risk of recurrence.

We prospectively studied 63 patients with nosocomial C difficile diarrhoea. Serial serum IgA, IgG, and IgM concentrations against C difficile toxin A, toxin B, or non-toxin antigens were measured by ELISA. Individuals were followed for 60 days.

19 patients died (30%). Of the 44 who survived, 22 had recurrent C difficile diarrhoea. Patients with a single episode of C difficile diarrhoea (n=22) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea (n=22, p=0·004). On day 12, serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea (n=7) than in those who subsequently had recurrent diarrhoea (n=9, p=0·009). The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A, measured 12 days after onset of C difficile diarrhoea, was 48·0 (95% CI 3·5–663).

A serum antibody response to toxin A, during an initial episode of C difficile diarrhoea, is associated with protection against recurrence.