prothionamide and Tuberculosis--Pulmonary

In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection.. STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites.. The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB.. This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.

Topics: Antitubercular Agents; Bangladesh; Clinical Protocols; Clofazimine; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Fluoroquinolones; Humans; Isoniazid; Kanamycin; Moxifloxacin; Prothionamide; Pyrazinamide; Research Design; Time Factors; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

To analyse the causes of multi-drug resistant tuberculosis (MDR-TB) and to evaluate the effects of chemotherapy with ofloxacin and other antituberculosis drugs.. 27 cases with MDR-TB were treated with the regimen of 3KPTHOX/PTHOX. Changes of sputum convesion, X-ray manifestations and side effects after the treatment were also evaluated.. 67% of the MDR-TB patients were due to irregular treatment, and 18% were caused by improper treatment. The sputum culture conversion rate at end of treatment was 89%. The bacteriological relapse rate of converted cases during 2 year follow-up was 8%.. MDR-TB might be prevented by a combination of health education and rational use of short-course chemotherapy. Ofloxacin and other second-line anti-tuberculosis drugs are effective and were tolerated in treating patients with MDR-TB.

Topics: Adult; Aminosalicylic Acid; Anti-Infective Agents; Antitubercular Agents; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Kanamycin; Male; Middle Aged; Ofloxacin; Prothionamide; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Schoolchildren were Mantoux-tested with 2 TU freeze-dried PPD RT23, and the strong reactors with indurations of 14.0 mm or more were selected for treatment with one of three different fixed drug combinations containing isoniazid or with placebo for 2 to 6 months. The initial tuberculin test was repeated after 8, 14, and 27 months. Of the 8,934 black schoolchildren initially tested, 5,165 did not react to the skin test, 2,898 had indurations up to 14.0 mm, and 871 reacted strongly. Of these strong reactors, 808 were allocated to four preventive treatment groups. On completion of treatment, the mean tuberculin reaction for all groups was significantly decreased. Because the placebo group showed changes similar to those seen in the other treatment groups, the tuberculin skin test is probably not suitable for monitoring the success of preventive therapy. Differences between skin test results before and after treatment when retesting only strong reactors are caused by a combination of effects that are difficult to distinguish. Assuming random variation in tuberculin sensitivity, the decrease can be explained as a combined effect of regression to the mean and some boosting. The increased reaction sizes in the subsequent Mantoux tests are explained by the booster phenomenon and possibly by reinfection. When using a cutting point for deriving a positive reactor, the chance of being selected for preventive treatment may depend primarily on the moment in time when the test is done. Thus, all reactors with no recent BCG vaccination should equally be considered for treatment.

Topics: Adolescent; Child; Dapsone; Drug Combinations; Ethambutol; Female; Humans; Hypersensitivity, Delayed; Isoniazid; Male; Placebos; Prothionamide; Random Allocation; Rifampin; Tuberculin Test; Tuberculosis, Pulmonary

One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared. The daily regimen was rifampicin and ethambutol (RE7). The three intermittent regimens also contained rifampicin and ethambutol: one of them, rifampicin and ethambutol throughout (RE3); the next one supplemented with pyrazinamide for the first 3 months (REZ3); the last one supplemented with prothionamide for the first 3 months (REPt3). The pyrazinamide containing regimen was subdivided into ordinary and high dose groups. The subjects for retreatment were those who have had, at least, more than 6 months of initial triple chemotherapy of isoniazid, PAS and streptomycin at the health centres, and failed to convert to bacteriologically negative status. Among 419 patients who were available for sensitivity tests before commencing retreatment, 393 (94.3%) were resistant to isoniazid. Six hundred and seventy-four patients (674) were allocated randomly to the regimens: 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy. There remain 501 patients who completed their retreatment. As assessed at 12 months, a bacteriologically favourable response was achieved in 68% of 135 RE7 patients, 62% of 129 RE3 patients, 74% of 132 REZ3 patients, and in 79% of 108 REPt3 patients. Adverse reactions were uncommon: 4% in RE7, 5% in RE3 and 9% in REZ3, but 32% in REPt3. Relapse rates during 2 years after termination of chemotherapy were 15% in RE7, 14% in RE3 and REZ3, and 26% in REPt3, as calculated by life table analysis.

Topics: Adolescent; Adult; Antitubercular Agents; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Prothionamide; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

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; Antitubercular Agents; Child; Clinical Trials as Topic; Dapsone; Drug Combinations; Humans; Isoniazid; Isonicotinic Acids; Prothionamide; Tuberculosis, Pulmonary

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

In two groups, each of 40 patients, with previously untreated cavernous pulmonary tuberculosis the following treatment schemes were compared in a randomised clinical study: isoniazid, ethambutol, and rifampicin (control group) and isoprodian with rifampicin (study group). Bacteriologic and radiographic parameters showed that in the study group the results were at least as good as in the control group. Symptoms of drug intolerance were equally rare in both groups.

Topics: Dapsone; Drug Combinations; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Prothionamide; Rifampin; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Isoniazid; Isonicotinic Acids; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prothionamide; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Isoniazid; Isonicotinic Acids; Prothionamide; Tuberculosis, Pulmonary

Topics: Adult; Clinical Trials as Topic; Ethionamide; Female; Humans; India; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Evaluation; Humans; Isoniazid; Isonicotinic Acids; Male; Prothionamide; Tuberculosis, Pulmonary

Topics: Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Evaluation; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Prothionamide; Tuberculosis, Pulmonary

Topics: Adult; Aged; Clinical Trials as Topic; Dapsone; Drug Combinations; Drug Evaluation; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine's safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG's therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log

Topics: Amikacin; Animals; Antigens, Bacterial; Antitubercular Agents; BCG Vaccine; Disease Models, Animal; Drug Resistance, Bacterial; Levofloxacin; Mice, Inbred BALB C; Mice, SCID; Mycobacterium bovis; Mycobacterium tuberculosis; Plasmids; Prothionamide; Pyrazinamide; Tuberculosis, Pulmonary; Vaccines, Synthetic; Virulence

Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens. This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). In this study, we investigated the association between macrophage polarization and MDR-TB/XDR-TB and the association between macrophage polarization and the anti-TB drugs used.. iNOS and arginase-1, a surface marker of polarized macrophages, were quantified by immunohistochemical staining and imaging analysis of lung tissues of patients who underwent surgical treatment for pulmonary TB. Drug susceptibility/resistance and the type and timing of anti-tuberculosis drugs used were investigated.. The M2-like polarization rate and the ratio of the M2-like polarization rate to the M1-like polarization rate were significantly higher in the MDR-TB/XDR-TB group than in the DS-TB group. The association between a high M2-like polarization rate and MDR-TB/XDR-TB was more pronounced in patients with a low M1-like polarization rate. Younger age and a higher M2-like polarization rate were independent associated factors for MDR-TB/XDR-TB. The M2-like polarization rate was significantly higher in patients who received anti-TB drugs containing pyrazinamide continuously for 4 or 6 weeks than in those who received anti-TB drugs not containing pyrazinamide.. The M2-like polarization of macrophages is associated with MDR-TB/XDR-TB and anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.

Topics: Adult; Antitubercular Agents; Cycloserine; Extensively Drug-Resistant Tuberculosis; Female; Humans; Lung; Macrophage Activation; Macrophages; Male; Middle Aged; Mycobacterium tuberculosis; Prothionamide; Pyrazinamide; Treatment Failure; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Rifampin (RIF) mono-resistant tuberculosis (RMR-TB) is a rare disease. Current guidelines recommend that RMR-TB be treated as multidrug-resistant TB (MDR-TB) but the evidence is scarce.. We conducted a retrospective cohort study on pulmonary TB patients to investigate the characteristics and outcomes of RMR-TB. The characteristics of RMR-TB were compared with those with adverse events to rifampin (RAE-TB).. Forty-four RMR-TB and 29 RAE-TB patients were enrolled. RMR-TB patients showed more alcohol use, prior history of TB, and radiologically severe disease, while RAE-TB patients were older and had more comorbidities and combined extrapulmonary TB. A fluoroquinolone (FQ) was the drug most commonly added (70.5%, RMR-TB; 82.8%, RAE-TB). Median treatment duration was 453 days in RMR-TB and 371 days in RAE-TB (p = 0.001) and treatment success rates were 87.2% (34/39) and 80.0% (20/25), respectively (p = 0.586). Subanalysis of the RMR-TB group by treatment regimen (standard regimen [n = 11], standard regimen + FQ [n = 12], MDR-TB regimen [n = 21]) revealed a higher rate of radiologically severe disease in the MDR-TB subgroup, with similar treatment success rates for the subgroups (85.7% [6/7]), 91.7% [11/12], and 85.0% [17/20], respectively) despite different durations of treatment (345, 405, and 528 days, respectively). Two recurrences (33.3% [2/6]) developed only in standard regimen subgroup, suggesting that standard regimen is not enough to treat RMR-TB patients.. The treatment outcome of RMR-TB with 1

Topics: Adult; Age Distribution; Aged; Alcohol Drinking; Aminosalicylic Acid; Antitubercular Agents; Cohort Studies; Comorbidity; Cycloserine; Ethambutol; Female; Fluoroquinolones; HIV Infections; Humans; Isoniazid; Male; Middle Aged; Prothionamide; Pyrazinamide; Republic of Korea; Retrospective Studies; Rifampin; Severity of Illness Index; Treatment Outcome; Tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected isolates were used to determine antibiotic susceptibility patterns against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin, capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57 new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5% of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR-TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug-resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR-TB, which is higher than the average numbers in China (about 8%) and in the world (9.6%). This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes.

Topics: Aminoglycosides; Aminosalicylic Acid; Antitubercular Agents; Capreomycin; China; Drug Resistance, Multiple, Bacterial; Extensively Drug-Resistant Tuberculosis; Fluoroquinolones; Humans; Incidence; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prothionamide; Tuberculosis, Pulmonary

Since 1990, the tuberculosis incidence rate in Eastern Europe and post-Soviet republics has been increasing in many countries including Kazakhstan. This problem is particularly important in Kazakhstan regions with limited financial resources, among them - in South Kazakhstan province. The aim of this study was to investigate the main clinical and antibiotic-related economic aspects of tuberculosis treatment in South Kazakhstan province.. In total, 502 patients participated in the study. They were hospitalized to the tuberculosis dispensary of Sayram district (South Kazakhstan province) in 2007-2013. Statistical analysis included logistic regression for better treatment outcomes and analysis of antibiotic treatment costs.. Two-thirds of patients had infiltrative tuberculosis (67%). Positive treatment outcomes were determined in 85% of cases. The patients were mostly treated with cycloserine, protionamide, capreomycin, and ofloxacin. The majority of antibiotic costs were related to the treatment with capreomycin. In case of the positive results of the test for Mycobacterium tuberculosis, antibiotic expenses were almost 3 times greater than in case of negative test results (P<0.001).. The majority of patients had extensively drug-resistant tuberculosis. The negative results of the test for Mycobacterium tuberculosis at discharge were not related to pretreatment factors. Antibiotic-related costs were significantly higher in case of the positive results of the test of Mycobacterium tuberculosis, but were not associated with gender, residence place, hospitalization recurrence, or main blood test results before treatment.

Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Capreomycin; Cycloserine; Drug Costs; Female; Humans; Kazakhstan; Male; Middle Aged; Ofloxacin; Prothionamide; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

The limited experience in treating patients with extensively drug-resistant tuberculosis (XDR-TB) shows a therapeutic success rate under 50-60% and there are no publications regarding the outcome of these patients treated with standardized regimens. All multidrug-resistant tuberculosis (MDR-TB) patients hospitalized at the Masih Daneshvari Hospital in Tehran, Iran, during 2004-2007 were recruited. Drug susceptibility testing to 14 drugs (including eight second-line drugs) was performed and a standardized regimen with ofloxacin, cycloserine, prothionamide, and amikacin was administered for all patients. Outcome of the patients was studied, comparing between the MDR-TB non-XDR-TB and the XDR-TB. Fifty-one patients were included, 12 with XDR-TB criteria. Of 51, 48 were HIV negative and HIV status was unknown in three cases. All 12 were HIV negative. XDR-TB infection was significantly associated only with age (p = 0.039). The success rates for the total 51 MDR-TB, the 39 MDR-TB non-XDR-TB, and the 12 XDR-TB patients were 76.5% (39 patients), 87.2% (34 patients), and 41.7% (5 patients), respectively. Resistance to ofloxacin, ciprofloxacin, and amikacin were found to be significantly associated with unsuccessful outcome. In this setting, a standardized second-line drugs regimen produces high treatment success rates in MDR-TB patients unless XDR-TB is present.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Clinical Protocols; Cycloserine; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Female; Humans; Iran; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Ofloxacin; Prothionamide; Treatment Outcome; Tuberculosis, Pulmonary

Timely and intensive monitoring for, and management of, adverse effects caused by anti-tuberculosis drugs are essential components of control programs for multidrug-resistant tuberculosis (MDR-TB). This retrospective case series was conducted in northern Taiwan from January 2007 to December 2008 at Taipei Medical University-Wan Fang Hospital, a 750-bed tertiary-care center and MDR-TB referral center. Hepatitis associated with prothionamide was defined as the recurrence of hepatitis after a second prothionamide treatment re-challenge. In total, 47 patients with MDR-TB enrolled in the Directly Observed Therapy, Short Course-Plus Program were identified during the study period, and 44 (93.6%) were treated with prothionamide. Seven of these 44 patients (15.9%) developed hepatitis after being treated with prothionamide concurrent with other anti-tuberculosis agents. Hepatitis associated with prothionamide occurred in three of these seven patients (6.8%). In these three patients, hepatitis developed following treatment with prothionamide for 28 days, 39 days or 45 days. Hepatitis developed rapidly after re-challenge with prothionamide at 4 days, 4 days and 3 days, respectively. Liver function returned to the normal range after cessation of prothionamide treatment for 19 days, 27 days or 28 days. Close monitoring of liver function was necessary in MDR-TB patients who received prothionamide treatment.

Topics: Antitubercular Agents; Bilirubin; Chemical and Drug Induced Liver Injury; Drug Monitoring; Humans; Mycobacterium tuberculosis; Prothionamide; Retrospective Studies; Taiwan; Transaminases; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Withholding Treatment

The efficiency of treatment was analyzed in 142 children aged 3-14 years who had local forms of primary pulmonary tuberculosis. Therapy was performed according to regimens 3 and 1, by using individual dosage regimens depending on the extent and severity of a specific process, the presence of complications, and age-related features. In minor tuberculosis, solitary calcifications being detected without signs of the activity of tuberculous infection, the basic course of therapy was 6-8 months; it was performed using 2 drugs in individual cases. In disseminated and complicated processes, eliminated intoxication and visible X-ray inflammatory changes were observed in 58.8-61.7% of children by months 3-4 of treatment, which required a longer intensive phase, by administering 3 drugs in the continuation phase till 6-9 months.

Topics: Adolescent; Age Factors; Antibiotics, Antitubercular; Antitubercular Agents; Child; Child, Preschool; Cycloserine; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Prothionamide; Pyrazinamide; Radiography, Thoracic; Rifampin; Streptomycin; Time Factors; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary

National Masan Tuberculosis Hospital, Masan, South Korea, a 430-bed tertiary referral hospital specializing in tuberculosis.. To evaluate the treatment outcomes of standardized, empiric regimens for multidrug-resistant tuberculosis (MDR-TB).. A retrospective analysis of the hospital records of 142 patients with MDR-TB who had failed short-course chemotherapy. Between 1 January 1998 and 30 June 2000, patients were started on one of two standardized, empiric regimens based on previous treatment history. Drug susceptibility testing of the infecting strain was not used to modify the treatment regimen. Treatment was continued for at least 18 months after conversion to a negative culture.. Sixty-three patients (44.1%) were cured and discharged from treatment after at least 18 months of negative cultures; 18 (12.7%) failed treatment, 41 (28.9%) defaulted, four died (2.8%), and 15 (10.6%) were transferred to another institution. One patient is still on treatment. Resistance to ofloxacin was the only risk factor related to poor outcome (death or failure) in univariate or multiple logistic regression analysis.. High levels of resistance to second-line drugs are likely a cause of poor outcome of MDR-TB therapy in Korea. Directly observed therapy and other methods to increase patient compliance should be considered nationwide, as they may improve MDR-TB treatment outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminosalicylic Acid; Antitubercular Agents; Cohort Studies; Cycloserine; Female; Humans; Kanamycin; Korea; Male; Middle Aged; Ofloxacin; Prothionamide; Pyrazinamide; Retrospective Studies; Self Administration; Streptomycin; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Multiresistant tuberculoses are on the increase. The conversion rates in "additional" therapy are only modest. 17 multiresistant patients and 6 treatment-refractory tuberculoses were treated by us with ofloxacin-cycloserin-protionamide-INH. 16 of these patients were HIV positive. 21 patients converted after 3 months of treatment by the latest. 3 patients died of HIV syndrome. There was otherwise no difference between HIV positive and HIV negative patients. As a rule, the combination was well tolerated. In multiresistant tuberculosis, it is mandatory to administer at least 3 drugs to which there is no resistance.

Topics: Adult; AIDS-Related Opportunistic Infections; Cycloserine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Ofloxacin; Prothionamide; Recurrence; Sputum; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: Adult; Antitubercular Agents; Ethambutol; Female; Follow-Up Studies; Humans; Inpatients; Isoniazid; Male; Outpatients; Pregnancy; Prothionamide; Pyrazinamide; Rifampin; Streptomycin; Time Factors; Tuberculosis, Pulmonary

This is a report on 912 patients treated during 1973 to 1979 for pulmonary tuberculosis and/or extrapulmonary organ involvement. These patients had been treated with a fixed tablet combination of isoniacide, prothionamide and diaphenyl sulfone in association with rifampicin and partly other substances. It was the aim of our study to examine this form of therapy in respect of side effects and effectivity. 535 of these 912 patients were followed up for as long as 13 years (maximum follow-up period). According to the criteria of the American Tuberculosis and Respiratory Diseases Association the patients were suffering from 182 cases of pulmonary tuberculosis of only slight extension, 490 of moderate extension and 130 of large extension, as well as 55 cases of pleuritis, 67 extrapulmonary organ tuberculoses and 1 tuberculosis of the bronchial mucosa. Allergic skin reactions occurred in 0.7% of the cases, and in 0.9% there were neurological disturbances such as vertigo, paroxysms and polyneuropathies. In 7.4% of the patients there was an increase in serum enzyme activities of SGOT, SGPT, Y-GT as a sign of hepatotoxicity. In 5.5% of the patients there were several gastrointestinal concomitant phenomena such as sensation of fullness, nausea, and vomiting. Under IPD therapy the hemoglobin valuedropped on the average by 12% up to the 5th or 6th week of treatment and rose subsequently to almost normal levels. No permanent damage was seen in any of the patients under observation. In the moderately extended tuberculosis cases disinfection occurred on the average between the 6th and 8th week of treatment, in the greatly extended cases on the average in the 9th to 13th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Isoniazid; Isonicotinic Acids; Long-Term Care; Male; Prothionamide; Rifampin; Tuberculosis, Pulmonary

An increase in the number of patients attending the Victoria Infirmary, Glasgow with isoniazid resistant tuberculosis, prompted a survey of the incidence of the condition in Glasgow. There was a clustering of cases among the homeless and/or alcoholic population of the city, particularly between the years 1982 and 1986. This suggests an outbreak of isoniazid resistance among that population, probably spread from a single, but unidentified source.

Topics: Alcoholism; Cluster Analysis; Disease Outbreaks; Drug Resistance, Microbial; Female; Humans; Ill-Housed Persons; Isoniazid; Male; Mycobacterium tuberculosis; Prothionamide; Scotland; Tuberculosis, Pulmonary

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: Animals; Dapsone; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Prothionamide; Tuberculosis, Pulmonary

Topics: Adolescent; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Prothionamide; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Clinical manifestations including rheumatoid changes, lymph node swelling, fever, butterfly rash, anaemia and leukopenia had developed gradually over a period of years in a 46-year-old female patient. Due to these findings systemic lupus erythematosus (SLE) was suspected. Further diagnostic procedures revealed concomitant pulmonary tuberculosis. In the course of the tuberculostatic therapy, there occurred six episodes of marked exacerbation of drug-induced SLE signs and symptoms including fever, myalgia, swelling of joints, butterfly rash and high titers of antinuclear antibodies. These exacerbations were induced by single-agent or combination therapy with ethambutol, pyrazinamide, streptomycin and/or prothionamide and resolved readily after discontinuation of the drug(s). With concomitant use of hydroxychloroquine sulfate, a combination therapy with rifampicin and cycloserine did not give rise to further complications although the autoantibodies persisted. This treatment regimen was given until clinical cure was achieved.

Topics: Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Lupus Erythematosus, Systemic; Middle Aged; Prothionamide; Pyrazinamide; Streptomycin; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Prothionamide; Rifampin; Tuberculosis, Pulmonary

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

To determine whether or not low dosage prothionamide (PTH), with or without diamino diphenyl sulphone (DDS), can replace PAS or thiacetazone as the companion drug to isoniazid (INH) in the treatment of tuberculosis, two experiments have been performed in mice. In experiment I the 2-month effectiveness of 25mg/kg INH alone, INH+PTH (25mg/kg) or INH+PTH+DDS (10mg/kg) was investigated. Both PTH-containing regimens were equally effective in preventing the selection of INH-resistant mutants but PTH did not appear to add much to the bactericidal activity of INH. In experiment II the one year effectiveness of similar regimens supplemented by an initial month of streptomycin (SM) was investigated. Again PTH appeared very effective whereas DDS seemed ineffective. Therefore it seems that PTH is likely to be a good companion drug for INH when used in man at the dosage of 5mg/kg which is more or less equivalent to 25mg/kg in the mouse.

Topics: Animals; Dapsone; Drug Administration Schedule; Drug Therapy, Combination; Female; Isoniazid; Isonicotinic Acids; Mice; Prothionamide; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; L Forms; Male; Middle Aged; Mycobacterium tuberculosis; Prothionamide; Rifampin; Time Factors; Tuberculosis, Pulmonary

Experimental and clinical studies showed that there were rapidly and slowly growing, as well as persisting mycobacteria, including variants in L-forms. Combinations of isoniazid, streptomycin and PAS mainly affected rapidly growing variants of mycobacteria, while isoniazid and rifampicin in combination with streptomycin, protionamide or ethambutol had the most pronounced bacteriostatic effect on all mycobacterial variants. Discontinuation of the bacteria isolation was observed by the end of the 4th, 6th and 9th months of the treatment in 73.9, 93 and 96 per cent of the newly recorded patients with cavernous tuberculosis respectively. Closing of the caverns in the same periods was observed in 26.1, 68.4 and 81.4 per cent of the patients. In patients with rapid discontinuation of the bacteria isolation, i. e. within the first 3 months of the treatment a rapid closing of the caverns was also recorded.

Topics: Aminosalicylic Acid; Animals; Antitubercular Agents; Drug Evaluation; Drug Evaluation, Preclinical; Drug Therapy, Combination; Ethambutol; Guinea Pigs; Humans; Isoniazid; Mice; Prothionamide; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Prothionamide; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Animals; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Guinea Pigs; Isoniazid; Prothionamide; Rabbits; Rats; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Adult; Ambulatory Care; Dapsone; Drug Combinations; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

Topics: Aged; Drug Therapy, Combination; Ethambutol; Female; Humans; Kanamycin; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

The results of combination therapy of Isoprodian with ethambul in patients with severe pulmonary tuberculosis were found to be comparable with the results previously obtained by us with other first-choice therapeutic regimens. 61% of the 140 cavities found before treatment disappeared within 5 months and 74% within 8 months of therapy. Disappearance of bacilli from the sputum was demonstrated in 89% of the patients by 12 weeks and in all patients by 20 weeks of treatment. The satisfactory therapeutic results, the low toxicity, the convenience of administration and, moreover, the economic aspect of the relatively lower cost of Isoprodian therapy justify the further use of Isoprodian supplemented with a first-choice tuberculostatic drug in the initial phase of treatment followed by long-term therapy with Isoprodian on its own in the stabilizing phase of even severe cases of tuberculosis.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Dapsone; Drug Combinations; Drug Evaluation; Drug Resistance, Microbial; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Sputum; Tuberculosis, Pulmonary

Isoprodiane (a combination of isoniazid, prothionamide and dapsone) was given to 22 persons with open cavitating pulmonary tuberculosis. None of them had been treated before. Microscopic and cultural sputum conversion occurred within an average of 5 and 11 weeks respectively. Treatment was discontinued in five patients: as a safety measure, despite sputum conversion, on account of the extent of the process and the general condition of the patient (one case); because of side-effects (two cases, one of whom was hypersensitive to isoniazid); because the patients failed to continue with the treatment (two cases). The early results were very promising; the long-term results cannot yet be assessed. The therapy did not materially affect the haemoglobin levels.

Topics: Adolescent; Adult; Dapsone; Drug Combinations; Drug Evaluation; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Dapsone; Drug Combinations; Drug Evaluation; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Mycobacterium tuberculosis; Prothionamide; Sputum; Tuberculosis, Pulmonary

Topics: Adult; Cycloserine; Dapsone; Drug Combinations; Humans; Isoniazid; Isonicotinic Acids; Male; Mycobacterium avium; Prothionamide; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Prothionamide; Rifampin; Tuberculosis, Pulmonary

Topics: Adolescent; Age Factors; Child; Child, Preschool; Dapsone; Drug Combinations; Drug Evaluation; Humans; Infant; Infant, Newborn; Isoniazid; Isonicotinic Acids; Prothionamide; Tuberculosis, Pulmonary

Topics: Czechoslovakia; Ethambutol; Humans; Oxazoles; Phenylthiourea; Prothionamide; Rifampin; Thiosemicarbazones; Tuberculosis, Pulmonary

Topics: Adult; Antitubercular Agents; Dapsone; Drug Combinations; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Isonicotinic Acids; Male; Prothionamide; Time Factors; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Humans; Kanamycin; Prothionamide; Pyrazinamide; Tuberculosis, Pulmonary; Viomycin

Topics: Adolescent; Adult; Biological Availability; Ethionamide; Female; Humans; Isonicotinic Acids; Male; Middle Aged; Polarography; Prothionamide; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Dapsone; Drug Synergism; Humans; Isoniazid; Prothionamide; Tuberculosis, Pulmonary

Topics: Adult; Aged; Blood; Blood Cell Count; Dapsone; Drug Combinations; Female; Hematocrit; Hemoglobinometry; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Dapsone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Prothionamide; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Asthenia; Depression; Humans; Isonicotinic Acids; Male; Prothionamide; Syndrome; Tuberculosis, Pulmonary

Topics: Blood Bactericidal Activity; Drug Therapy, Combination; Ethionamide; Humans; Isonicotinic Acids; Prothionamide; Tuberculosis, Pulmonary