Prevention of Clostridium difficile (C. difficile) Diarrhea with Probiotic in Hospitalized Patients Treated with Antibiotics

PURPOSE: C. difficile diarrhea is a common health problem justifying treatment efforts to reduce its occurrence. Because of the relatively poor response to current therapy, additional approaches for prevention and/or treatment are warranted. There is no support for primary prophylaxis for C. difficile infection, but Saccharomyces boulardii can be used to decrease recurrences. (Surawicz et al, Clin Infect Dis. 2000; 31:1012-1017).The aim of this study was to determine the efficacy of probiotic (Lactobacillus acidophilus 80%, Lactobacillus bulgaricus 10%, Bifidobacterium Biffidum 5%, S. Thermophilus 5%) to prevent C. difficile diarrhea in hospitalized patients who were receiving antibiotics. METHODS: 100 in-patients, receiving oral or intravenous antibiotics, were enrolled in a prospective randomized trial with two groups; A control group and a treatment group, with similar age and sex distribution. The treatment group was started on daily probiotic therapy (Lactobacillus 500mg- 2 caplets tid) from the start of antibiotic therapy until hospital discharge. Data were collected on age, sex, class of antibiotic used, CBC, CMP, and proton pump inhibitor (PPI) use. Patients were monitored for fever, leukocytosis, development of diarrhea, abdominal distension, constipation and abdominal pain. Stool specimens from patients with these symptoms were sent for C. difficile toxin assay. Student t-tests and chi-square analysis compared differences in means or proportions between both groups. Additional logistic regression analyses tested for risk factors related to C. difficile infection. RESULTS: We observed that 22/55 patients without probiotic and 5/45 patients with probiotic developed C. difficile diarrhea (P=.001). Regardless of treatment, it occurred more frequently in older patients (71 ± 17(sd) yrs vs. 59 ± 19 yrs; P=.0062). Occurrence was higher among patients using PPI(45% of PPI users vs. 15% of PPI non-users; P=.001). Both admission Hematocrit and albumin were significantly lower in C. difficile patients; P=.0341 & P=.0010, respectively). Logistic regression analysis further determined 83% decreased risk with probiotic use (P=.012), plus an independent 5% increased risks for every 1-year increase in age of the patient starting with age 19 years (P=.011), 6.8-fold increased risk among PPI users (P=.005) plus a 6.6-fold increased risk among patients diagnosed with sepsis (P=.021). CONCLUSION: Probiotic significantly reduced C.difficile diarrhea in hospitalized patients receiving antibiotics. Increasing age, sepsis and use of PPI were associated with increased risk of C. difficile diarrhea.