Background: Spontaneous bacterial peritonitis (SBP) may occur despite antibiotic prophylaxis. We investigated whether the addition of probiotics to norfloxacin enhances its efficacy in the prevention of SBP.
Methods: A double-blind, randomized-controlled trial was conducted among consecutive cirrhotic patients who had either recovered from SBP (secondary prophylaxis) or who were at a high risk for the development of SBP (low ascitic fluid protein or serum bilirubin ≥ 2.5 mg/dl; primary prophylaxis). Norfloxacin 400 mg/day with probiotics capsules (Enterococcus faecalis JPC 30 million, Clostridium butyricum 2 million, Bacillus mesentericus JPC 1 million, Bacillus coagulans 50 million spores) at a dose of two capsules three times daily (group 1) or norfloxacin with a placebo (group 2) was given and the occurrence of SBP within a period of 6 months (primary endpoint) or side-effects of therapy and mortality (secondary endpoints) were recorded.
Results: From April 2005 through August 2007, 110 patients were randomized to group 1 (n=55) or group 2 (n=55) and 45 (82%) and 43 (78%) of them completed the trial, respectively. The baseline characteristics were comparable. On intention-to-treat analysis, the cumulative probability of treatment failures was similar in both the groups [19/55 (34%) in group 1 vs. 20/55 (36%) in group 2, P=0.840]. The cumulative probability of mortality was also similar [13/45 (29%) in group 1 vs. 14/43 (32%) in group 2, P=0.834]. The frequency of side-effects was also comparable. In subgroup analyses, the frequencies of SBP and deaths were similar in the two groups in the subgroups of primary and secondary prophylaxes. The presence of encephalopathy and serum bilirubin of greater than 3.65 mg/dl were found to predict mortality independently.
Conclusion: The addition of probiotics to norfloxacin does not improve its efficacy in primary or secondary prophylaxis of SBP or in reducing the mortality in cirrhotic patients with ascites.