OBJECTIVE--To determine the safety and efficacy of a new combination treatment for patients with Clostridium difficile-associated disease (CDD). The treatment combines the yeast Saccharomyces boulardii with an antibiotic (vancomycin hydrochloride or metronidazole). DESIGN--A double-blind, randomized, placebo-controlled, parallel-group intervention study in patients with active CDD. Patients received standard antibiotics and S boulardii or placebo for 4 weeks, and were followed up for an additional 4 weeks after therapy. Effectiveness was determined by comparing the recurrence of CDD in the two groups using multivariate analysis to control for other risk factors for CDD. SETTING--National referral study of ambulatory or hospitalized patients from three main study coordinating centers. PATIENTS--A total of 124 eligible consenting adult patients, including 64 who were enrolled with an initial episode of CDD, and 60 who had a history of at least one prior CDD episode. Patients who were immunosuppressed due to acquired immunodeficiency syndrome or cancer chemotherapy within 3 months were not eligible. INTERVENTION--Treatment with oral S boulardii (1 g/d for 4 weeks) or placebo in combination with a standard antibiotic. MAIN OUTCOME MEASURE--Recurrence of active CDD. RESULTS--A history of CDD episodes dramatically increased the likelihood of further recurrences. Multivariate analysis revealed that patients treated with S boulardii and standard antibiotics had a significantly lower relative risk (RR) of CDD recurrence (RR, 0.43; 95% confidence interval, 0.20 to 0.97) compared with placebo and standard antibiotics. The efficacy of S boulardii was significant (recurrence rate 34.6%, compared with 64.7% on placebo; P = .04) in patients with recurrent CDD, but not in patients with initial CDD (recurrence rate 19.3% compared with 24.2% on placebo; P = .86). There were no serious adverse reactions associated with S boulardii. CONCLUSIONS--The combination of standard antibiotics and S boulardii was shown to be an effective and safe therapy for these patients with recurrent CDD; no benefit of S boulardii was demonstrated for those with an initial episode of CDD.

Fifty-four patients with chronic progressive multiple sclerosis received prednisone plus oral low-dose cyclophosphamide and either true plasmapheresis (PP) or "sham" PP weekly for 20 weeks in a double-blind controlled study. Immunosuppressive drug therapy alone (sham PP group, n = 29) was associated with improvement (greater than or equal to one step in Kurtzke Disability Status Scale [DSS]; mean change of 1.5) in 8 and stabilization of MS in 18 patients, with this status sustained in 23 patients at follow-up, 11 months after entry. In contrast, 14 of 26 patients who received "true" PP improved (greater than or equal to one step in DSS; mean change of 2.6), and 11 more were stable, with these changes sustained in 23 of 26 patients at follow-up. These differences, overall, between the PP and sham PP groups were significant at p less than 0.007.

Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.

We report the clinical, radiologic, and pathologic features of a patient who had fulminant demyelinating disease and who experienced acute progression of his disease after an episode of valproate-induced hyperammonemic encephalopathy. The role hyperammonemia played in the progression of the demyelination is uncertain. This case raises concern of a possible risk with the use of valproic acid in the subset of patients with fulminant demyelinating disease.

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