Antibiotic-associated diarrhoea (AAD) is a frequent complication of systemic antibiotic therapy and Clostridium difficile-associated diarrhoea (CDAD) is its most serious form due to associated morbidity and mortality.

This trial aimed to investigate whether the probiotic VSL#3 prevents AAD and CDAD in average-risk hospital patients.

Adult hospital inpatients exposed to systemic antibiotics were recruited to this multicentre, randomized, double-blind, placebo-controlled trial. One sachet of VSL#3 or placebo was given twice daily for the length of the antibiotics course and for seven days thereafter. Primary outcomes were AAD and CDAD.

Patients randomized to active (N = 117) and placebo (N = 112) groups were well-matched for baseline demographic patient data. No cases of CDAD were detected. The rate of AAD was significantly lower in the active group on per protocol analysis (0% active vs 11.4% placebo; P = 0.006). On intention-to-treat analysis the difference in AAD incidence (4.3% active vs 8.9% placebo; P = 0.19) was not significant.

VSL#3 is associated with a significant reduction in the incidence of AAD in average-risk hospital inpatients exposed to systemic antibiotics. As the incidence of CDAD has fallen sharply, no cases of CDAD were found. Probiotic administration as prophylaxis for CDAD may not be indicated in average-risk hospital patients.