rifampin and isoprodian

In order to assess the potential additive liver toxicity of isoniazid to that of a thioamide-containing treatment, a prospective, randomized, double-blind trial of 24 weeks' duration involving 772 adult patients was conducted in four leprosy centers--two in India, one in Madagascar, and one in the Ivory Coast. Patients with multibacillary leprosy were given daily 100 mg dapsone (DDS) and 350 mg prothionamide (PTH) plus monthly 600 mg rifampin (RMP) in combination either with 350 mg isoniazid (INH) or with a placebo. After clinical and laboratory (including HBs-Ag testing) examinations on admission, the side effects (especially gastrointestinal disturbances and liver toxicity) were assessed at regular intervals during treatment by laboratory testing (aminotransferases, bilirubin, alkaline phosphatase) and by recording spontaneous complaints. Analysis of the frequency and seriousness of the side effects was made before breaking the code (with or without INH). Although 10% of the patients had liver toxicity leading to stopping treatment, no significant difference in the occurrence of side effects was observed between patients treated with or without INH. Most (75%) of the observed side effects occurred during the first 4 weeks of treatment, and the time of their onset was not related to INH. Body weight and age were factors related to the frequency of side effects [the higher the body weight, the lesser the rate of side effects (p = 0.03)] and the rate of serious side effects increased with age (p = 0.02). But, again, the frequency of the side effects was not related to INH administration. Therefore, from the present study it can be concluded that INH does not increase the toxicity of the thioamide-containing treatment.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Dapsone; Double-Blind Method; Drug Combinations; Female; Humans; Incidence; Isoniazid; Leprostatic Agents; Leprosy, Lepromatous; Liver Function Tests; Male; Middle Aged; Prospective Studies; Prothionamide; Rifampin

Three regimens of 9 months' duration, 2 containing Isoprodian (isoniazid, prothionamide and dapsone) and either rifampicin or pyrazinamide and the third, a former standard regimen, isoniazid, streptomycin and pyrazinamide, were allocated at random to 436 untreated African tuberculosis patients. In the course of the trial 83 were excluded for various reasons and 93 were lost. After 3 months of hospitalization, patients took either Isoprodian or isoniazid at home for 6 months and were then followed up for 24 months. The Isoprodian plus rifampicin regimen achieved 97% bacteriological cure, the Isoprodian plus pyrazinamide regimen 86% and the standard regimen 91%. Of 35 patients found to harbour drug-resistant strains 22 were cured. There were 15 relapses in all. Absconding was the most common cause of failure.

Topics: Adult; Aged; Antitubercular Agents; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Patient Compliance; Prothionamide; Pyrazinamide; Radiography; Recurrence; Rifampin; Sputum; Tuberculosis, Pulmonary

Topics: Adult; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prospective Studies; Prothionamide; Random Allocation; Rifampin

Topics: Adult; Aged; Antitubercular Agents; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Pyrazinamide; Radiography; Rifampin; Sputum; Time Factors; Tuberculosis, Pulmonary

The Malta Leprosy Eradication Project (MLEP) was proposed in 1971 by Freerksen with the aim of eradicating leprosy in Malta. The project involved re-treatment of all known cases in Malta as of 1972 and all new cases thereafter with a regimen consisting of Isoprodian (a combination of dapsone, prothionamide and isoniazid) and rifampicin for varying intervals depending on the severity of their disease and their response to treatment. Overall the response to therapy was excellent with an extremely low relapse rate. During the 30 years of the project the incidence of leprosy steadily decreased continuing a decline that had started at least two decades earlier and Freerksen declared the disease eradicated from Malta in 2001. Although given the long incubation period of leprosy cases may still be occasionally detected in the future, the disease has been basically eradicated at this time and there are no patients currently receiving treatment. This work was done at the leprosy clinic, Boffa Hospital, Floriana, Malta.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Leprostatic Agents; Leprosy; Male; Malta; Program Evaluation; Prothionamide; Rifampin; Treatment Outcome

In Paraguay, the National Leprosy/Tuberculosis Program is based on a combined chemotherapy with isoprodian and rifampicin. The aim of this descriptive study was to investigate the therapy durations used so far in the treatment of 475 leprosy patients and to analyze the criteria responsible for the wide-ranging differences in therapy durations. As initial criteria, the following parameters were identified to have a significant influence on the therapy duration: Patients never treated before or pretreated, clinical classification and initial bacteriological index (BI) value. During therapy, conditions like the attendance and BI decrease/year showed a significant correlation with the therapy duration. Even though the studied criteria did not allow to draw a definite conclusion with regard to an 'ideal' therapy duration, they proved to be reliable, as only 2 patients have relapsed so far.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Mycobacterium leprae; Paraguay; Patient Compliance; Prothionamide; Rifampin; Time Factors

Three different partly intermittent regimens were evaluated in order to assess the value of rifampicin (RMP) in the continuation phase of treatment for tuberculosis. Patients suffering from newly diagnosed culture-positive pulmonary tuberculosis were admitted to the trial. All were initially treated daily for 8 weeks with a quadruple combination including RMP. The intensive treatment phase was followed by twice-weekly intermittent treatment for 16 weeks with one of three different combinations, one containing RMP. Of 246 patients, 85 were withdrawn, 7 because of adverse events. At the end of treatment 127 of 135 patients (94,1%) from whom sputum results could be obtained, had negative sputum cultures, and 6 had one colony growth. Of 42 patients who had one or more positive sputum cultures during follow-up of 96 weeks, 6 belonged to the RMP group compared with 20 and 16 of the other groups (P = 0,0244). The results indicate that a combined daily/intermittent regimen containing RMP in both phases can be safely used, whereas a similar regimen with the same duration but not including RMP in the continuation phase, is inferior.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Dapsone; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Prothionamide; Pyrazinamide; Rifampin; Sputum; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Middle Aged; Prothionamide; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Evaluation Studies as Topic; Follow-Up Studies; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Malta; Prothionamide; Recurrence; Rifampin

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Paraguay; Prothionamide; Rifampin; Tuberculosis

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Leprostatic Agents; Leprosy; Male; Prothionamide; Rifampin; Tanzania

Topics: Clofazimine; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Mycobacterium leprae; Prothionamide; Rifampin

A group of 150 patients with sputum-positive pulmonary tuberculosis was treated with a regimen containing only orally administered drugs. Rifampicin and pyrazinamide were combined with Isoprodian, which contains isoniazid and also prothionamide and diaphenylsulphone. All the drugs were given daily for 5 months. Early analysis of the results shows 5 treatment failures, 27 relapses of pulmonary tuberculosis and another 17 patients who did not complete the prescribed regimen.

Topics: Administration, Oral; Antitubercular Agents; Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Male; Patient Compliance; Prothionamide; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Leprostatic Agents; Leprosy; Prothionamide; Rifampin