A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium djffcile-associated diarrhea (CDAD) was performed.Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. dfficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%o) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%o) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11). Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P = 0.059) appeared not to be cleared of C. diffcile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n ‫؍‬ 139) received 3 million units (MU) IFN-␣2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n ‫؍‬ 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n ‫؍‬ 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n ‫؍‬ 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P ‫؍‬ .04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P ‫؍‬ .03; group 1 ‫؍‬ 9%, group 4 ‫؍‬ 12%, P ‫؍‬ not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 ‫؍‬ 32%, group 2 ‫؍‬ 30%, group 3 ‫؍‬ 30%, group 4 ‫؍‬ 35%, P ‫؍‬ NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if Combination therapy (interferon [IFN] plus ribavirin) is the first-line therapy for naive patients with chronic hepatitis C 1,2 ; patients who have relapsed after an initial treatment with IFN alone can also be re-treated with good results. 3 Unfortunately, there is no therapeutic option for patients who have not responded to IFN and to date consensus conferences 4,5 have not recommended any therapeutic schedule for IFN nonresponders; these patients nevertheless represent a high percentage of patients.Re-treatment of nonresponders with higher dosages of IFN and/or more aggressive approaches is ineffective 5 or induces a low rate of sustained responders 6 ; recent trials with IFN plus ribavirin combination protocols 7-11 have given disappointing results, but the small number of patients recruited into the studies and the low dosage of IFN used have made the results questionable.To address the question of whether higher than standard IFN dosages associated with ribavirin and/or prolonged time of administration may improve the rate of sustained responses, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN alone. The study was designed to compare the efficacy and safety of IFN given at 3 million units (MU) and 5 MU 3 times a week (t.i.w.) plus ribavirin 1,000 mg given daily over treatment durations of 6 and 12 months. PATIENTS AND METHODSDefinition of Nonresponse. According to the Consensus Conference held in Paris, February 26 to 27,1999, nonresponse to IFN monotherapy is defined by abnormal alanine transaminase (ALT) levels or by the presence of hepatitis C virus (HCV)-RNA during therapy; breakthroughs durin...

The main clinical features of patients who developed pseudomembranous colitis (PMC) or Clostridium difficile-associated diarrhoea (CDAD) during their stay at the S. Anna General Hospital, Como, over the period February 1984 to May 1988, are reported. Forty patients developed either CDAD (ten cases) or PMC (30 cases). Twenty-seven (65.7%) had undergone surgery and 32 (80.0%) had received prolonged antibiotic treatment. Three patients (7.5%) were given three doses only of ceftriaxone. Five patients (12.5%) had not received any antibiotic treatment; but three were nursed in a bed next to a patient with PMC-CDAD. The number of cases diagnosed were correlated retrospectively with the cumulative consumption of different groups of antibiotics on wards in which PMC or CDAD occurred. A significant difference (P less than 0.01) between third generation cephalosporins (16 cases) and ureidopenicillins (one case), was found. Twenty-five patients were treated with oral vancomycin. Two died of the underlying disease and 23 were cured. The disease recurred clinically in three, and follow-up cultures were positive in another asymptomatic case. Fifteen patients (all PMC cases) were treated with oral teicoplanin. All were clinically cured and remained asymptomatic and all but one were also cleared of C. difficile. No adverse reactions were observed in patients given either drug. Third generation cephalosporins, even when administered as short-term perioperative prophylaxis, but not ureidopenicillins, are significantly associated with C. difficile-related diseases. Teicoplanin proved to be very effective and safe in the treatment of PMC, and should be further evaluated there.

Forty-seven patients affected by Clostridium difficile-associated disease were treated orally with either vancomycin (patients hospitalized from February 1984 to February 1987) or teicoplanin (from March 1987 to December 1988). All patients given teicoplanin remained asymptomatic after discontinuation of treatment, and all but one were also cleared of C. difficile. In the vancomycin group, clinical symptoms recurred in 3 of 23 evaluable patients, and follow-up cultures were positive in another asymptomatic case.

Two-hundred-ninety-nine hospital workers were randomly allocated to receive MSD hepatitis B vaccine in different injection sites and by different routes (intramuscularly by gluteal or deltoid injections or subcutaneously in the arm) or Pasteur vaccine subcutaneously. Highest rates of seroconversion and highest mean anti-HB, titres were found in subjects given MSD vaccine by intramuscular injection into the deltoid muscle.