Response to Zocco et al .

Abstract

We appreciate the comments raised by Drs Zocco, Garcovich, and Gasbarrini (1) concerning some potential limitations of our study. The study was primarily aimed at investigating the prevention of antibiotic-associated diarrhea (AAD) in elderly, fragile patients with relevant comorbidities. Older age is indeed recognized as one of the most important risk factors for increased prevalence and severity of both AAD and Clostridium difficile infection (CDI) (2,3,4). Patients like those who were enrolled in our study, that is, with a very old age (such as that commonly observed in most medical wards) and a huge burden of comorbidities, are at the highest risk of developing AAD and CDI, and were usually excluded in previous clinical trials. Therefore, we expected to obtain a higher incidence of AAD as compared with the 37% reported in the only meta-analysis available at that time (5), but we observed an actually much lower incidence (17%). We had decided a priori that, in order for prophylactic therapy to be clinically acceptable, the number of patients needed to be treated should not exceed five to avoid one case of AAD and 27 to avoid one case of CDI. In case of low risk of AAD and CDI, such as that recorded in our study, even if S. boulardii was 100% effective, then most people receiving prophylactic therapy would not receive any benefit. For this reason, we managed to stop the enrollment of patients at the achievement of the pre-defined number, without taking into consideration the number of observed events. However, we agree that our study does not exclude the possibility that S. boulardii might be of benefit for clinical contexts at higher risk of AAD and CDI.