SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Chequer-board titrations show that the in vitro activity of ciprofloxacin against Mycobacterium tuberculosis is independent of that of streptomycin, isoniazid, ethambutol and pyrazinamide and confirm that there is antagonism between ciprofloxacin and rifampicin.
Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months. The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community. A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin. There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone. For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series. However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.
The prevalence of primary antituberculosis drug resistance in Gujarat, as studied between 1983 and 1986, was found to be significantly high, especially for isoniazid (13.9%) and streptomycin (7.4%). Primary rifampicin and pyrazinamide resistance were not detected in any strain. The prevalence of rifampicin resistance among treatment failure and relapse cases of pulmonary tuberculosis increased significantly from 2.8% in 1980 to 37.3% in 1986. In about 95% of the rifampicin resistant strains there was also resistance to isoniazid or streptomycin or both: resistance to isoniazid was detected in more than 90%.
Cytogenetic analyses were carried out in lymphocytes of 15 untreated tuberculosis (tb) patients and 15 other tb patients who had received combined tuberculostatic chemotherapy HRZ (isoniazid+rifampicin+pyrazinamide) for 2 months. The frequency of chromosomal aberrations and sister-chromatid exchanges (SCEs) did not show any statistically significant differences in the patients before treatment and after exposure to combined HRZ therapy as compared to controls (p > 0.05). However, we observed that the mitotic index was significantly decreased in both groups (p < 0.05). Based on the results of the present study, we believe there is no indication for a chromosome damaging effect of HRZ and their metabolites in human lymphocytes in vivo after treatment of tuberculosis patients with optimum doses.
Cytogenetic effects of 4 common anti-tubercular drugs, isoniazid (H), streptomycin (S), rifampicin (R) and pyrazinamide (Z), in 3 different combinations (2 SHRZ, 2 HRZ and 2 H2R2Z2) were evaluated in the lymphocytes of tuberculosis patients undergoing chemotherapy, in order to estimate their mutagenic potential in combination. All 3 regimens showed an increased frequency of chromosomal aberrations after treatment compared to before treatment. These findings are of significance in the treatment of tuberculosis, as the drugs in question are observed to be mutagenic/clastogenic.
There is now considerable interest in the possible use of agents which can change blood flow in solid tumors and thereby alter the response of tumors to different treatments. In the current presentation we briefly review the types of agents which have the potential to modify tumor blood flow, using nicotinamide. hydralazine, and pyrazinamide as examples and illustrate how they can be used to improve the response of murine tumors to radiation, hyperthermia and cyclophosphamide.
The present study was undertaken to compare the efficacy, effectiveness and cost-effectiveness of three short-course regimens with a standard programme for treatment of new tuberculosis (TB) cases. The study was conducted by reviewing the results of TB treatment in 1642 newly diagnosed, sputum positive pulmonary TB patients with four drug regimens carried out in five zonal TB centres throughout Thailand in 1987-1989. Analysis showed that the three-short-course regimens were more cost-effective than the standard regimen from the perspective of both providers and patients. Among the three short-course programmes, isoniazid, rifampicin and pyrazinamide for 2 months, followed by isoniazid and rifampicin twice a week for 4 months was the most cost-effective (US$70.24/effectiveness from providers' perspective and US$103.31/effective from patients' perspective). The result of this study throws some light on the development of new policy options, with scarce health resources, in the treatment of tuberculosis by the National Tuberculosis Programme in Thailand.
A radiometric method using the "Bactec 460-TB" apparatus now enables rapid obtaining of drug-susceptibility data and differentiation of clinical mycobacterial specimens into those belonging to the Mycobacterium tuberculosis complex (comprised of M. tuberculosis, M. bovis, M. bovis BCG and M. africanum) and non-tuberculous mycobacteria, using a specific inhibitor (p-nitro-alpha-acetyl-amino-beta-hydroxypropiophenone). In the present work, further differentiation of the M. tuberculosis complex into 4 individual species was achieved using the susceptibility of strains to 1.25 micrograms/ml of thiophene-2-carboxylic acid hydrazide, 40 micrograms/ml of D-cycloserine, and 100 micrograms/ml of pyrazinamide.
BACKGROUND: Acute infection and inflammation of the nasolacrimal sac may complicate congenital obstruction of the nasolacrimal duct. Acute dacryocystitis is uncommon later and tuberculosis is exceptionally responsible for it. CASE REPORT: A 4 1/2 year-old boy was admitted because he suffered from acute left dacryocystitis with fever and cervical adenitis. Involvement of both lacrymal gland and lymph node persisted despite antibiotic and corticosteroid therapy. Needle biopsy of the lymph node showed presence of Mycobacterium tuberculosis and excision revealed caseating granulomas. The tuberculin skin test was positive while pulmonary tuberculosis was discovered in the patient's father. The patient was successfully given izoniazid, rifampin for 9 months and pyrazinamide for 2. Drainage of the sac area was necessary after 1 month of treatment followed by dacryocystorhinostomy. CONCLUSION: This rare case of tuberculous dacryocystitis permits to delineate the difficulties of ophthalmologic therapy.
SETTING: Blisterpacks might be used to present low cost intermittent regimens while maintaining an easily remembered daily frequency of opening blisters, by alternating blisters containing 2 of the drugs of a 4-drug regimen with blisters containing the remaining 2 drugs. OBJECTIVE: The efficacy of the alternating regimens was examined in murine tuberculosis. DESIGN: 2 weeks after infection with Mycobacterium tuberculosis H37Rv, groups of mice were treated with rifampicin (R) 15 mg/kg, isoniazid (H) 25 mg/kg, pyrazinamide (Z) 300 mg/kg, ethambutol (E) 100 mg/kg three times weekly (RHZE3); RH/ZE, an alternating regimen of RH on days 1, 3 and 5 of the week and ZE on days 2, 4 and 6, RZ/HE or RE/HZ. RESULTS: Spleen and lung bacillary counts at 7 and 12 weeks indicated large differences in the efficacy of the regimens: RZ/HE > RE/HZ > RHZE3 > RH/ZE. Serum assays showed that Rifampicin (RMP) levels were much lower after HRZE and slightly lower after RZ, RE and RH than after R alone, whereas levels were similar when R was given before the remaining drugs; also, the absorption of Z was slightly increased by R. A second experiment used the same 4 regimens but gave R before other drugs. The organ colony forming units counts at 6 and 12 weeks were then similar. A third experiment examined continuation phase regimens of R3, R2, R2H2 and R2H6 given after daily RHZ treatment for 4 weeks. It found R2H2 only slightly superior to R2H6 and R3 much better than R2. CONCLUSION: 1. Alternating initial phase regimens were as effective as conventional intermittent regimens. 2. R3H6 might be an optimal continuation phase regimen for blisterpacks.
SETTING: Tuberculosis may be diagnosed too late, especially in HIV-infected patients, with consequences on bacillus transmission and survival. Empiric antibuberculosis treatment (EATT) may be started before diagnosis of tuberculosis is confirmed. As rifampicin is a broad spectrum antibiotic, EATT including rifampicin may be effective in infections other than tuberculosis, leading to misdiagnosis. OBJECTIVE: To define the efficiency criteria of EATT with or without rifampicin. DESIGN: Between 1988 and 1991, 20 febrile patients with suspected tuberculosis (including 15 who were HIV-positive) were started on EATT in the absence of bacteriological or histological proof of tuberculosis. 10 patients (50%) received a 4-drug non-specific EATT including rifampicin, isoniazid, pyrazinamide and ethambutol, and 10 (50%), received a 3-drug specific EATT without rifampicin. RESULTS: In 10 patients (50%), the diagnosis of tuberculosis was confirmed by positive cultures within a mean of 32 days (15-57 days) after the beginning of EATT (group TB 1). Of the 10 patients whose cultures remained negative, 4 (20%) became afebrile and showed improvement under EATT (group TB 2), and 6 (30%) remained febrile and did not improve (group No TB). Patients from groups TB 1 and TB 2 became afebrile within a mean of 11 days (1-54 days). This delay was not different between patients receiving specific or non-specific EATT. In patients receiving specific EATT, rifampicin was added to the initial 3-drug treatment after resolution of fever. CONCLUSION: EATT appears to be a useful method for rapid presumptive diagnosis and treatment of tuberculosis.
SETTING: The Matiben Chest Clinic at the West Algiers University Teaching Hospital, and 3 outpatient clinics specializing in tuberculosis and lung disease in Algiers. OBJECTIVE: To determine the tolerance and efficacy of a fixed proportion combination of 3 antituberculosis drugs (per tablet: 50 mg isoniazid + 120 mg rifampicin + 300 mg pyrazinamide) given during the first 2 months of a daily 6-month chemotherapy regimen. DESIGN: Random prospective treatment trial comparing a group of 124 patients receiving the triple combination with another group of 126 patients receiving the 3 drugs separately during the initial treatment phase. The continuation phase was identical for the 2 groups. Comparison of tolerance in the first 2 months, and of the failure and relapse rates (respectively at the end of treatment and 24 months after the end of treatment). RESULTS: During the first 2 months side-effects were significantly more common in the group receiving the drugs separately. At the end of treatment and during the following 24 months there were no significant differences in the cumulative rates of observed failures and relapses (2% and 1%). CONCLUSION: The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven.
SETTING: Chest Clinics at Blackburn and Newham, UK. OBJECTIVE: To test the efficacy of a short-course regimen of 6 months rifampicin and isoniazid supplemented by 2 months initial pyrazinamide (2HRZ-4HR), in the treatment of smear and culture-negative pulmonary tuberculosis and tuberculous pleural effusion in routine clinical practice. DESIGN: The results of 152 patients with these forms of tuberculosis treated between 1981 and 1991 were analysed retrospectively. RESULTS: 127 patients, 65 with pleural effusion and 62 with culture-negative pulmonary tuberculosis, completed treatment as planned. 100 were followed up for a mean duration 20.5 months (range 4-72) for culture-negative disease and 14.6 months (range 3-46) for pleural effusion. There were no relapses, giving a relapse rate of 0% (95% confidence interval 0-3.62%). CONCLUSION: Unsupervised self-administered treatment with 2HRZ/4HR is a highly effective regimen for culture-negative pulmonary tuberculosis and tuberculous pleural effusion in service conditions.
SETTING: A medical facility for approximately 90,000 gold miners employed on 24 South African gold mines. OBJECTIVE: To establish the long-term risk attributable to silicosis of relapse from pulmonary tuberculosis treated with short-course chemotherapy. DESIGN: A consecutive sample of gold miners with pulmonary tuberculosis allocated to receive rifampicin, isoniazid, pyrazinamide and streptomycin given on weekdays for 5 months. Radiographs were assessed at the time of diagnosis for the presence of silicosis. All of the men were followed for at least 5 years after completing their treatment, or until they left mine service or suffered a relapse of tuberculosis. RESULTS: The sample included 549 men of whom 167 had silicosis. The incidence density for relapse in silicosis was 1.55 (95% CI 0.97, 2.48) times that for the men without silicosis. There was no difference in the pattern of relapse over time between the two groups: the mean period to relapse in the men with silicosis was 2.6 years (SD 1.89 years) and for the men without silicosis was 3.1 years (SD 2.23 years) (P = 0.6). CONCLUSION: Silicosis causes a small increase in the risk of relapse of tuberculosis. Relapses in both groups were not confined to the first 2 years after completion of treatment.
BACKGROUND: Two months of rifampin and pyrazinamide (RIF/PZA) for tuberculosis prevention has been advocated as a way to improve adherence in mobile populations, such as recent immigrants. However, RIF/PZA requires intensive patient and laboratory monitoring for hepatotoxicity. OBJECTIVES: To describe the feasibility and outcomes of using RIF/PZA for TB prevention during a tuberculosis outbreak in a Mexican immigrant community, where 23 adults and 11 children were treated with RIF/PZA between August 2001 and October 2001. METHODS: Retrospective chart review and interviews with health department employees were conducted to assess completion rates, hepatotoxicity, cost, and feasibility of monitoring. RESULTS: Ten (91%) children and 13 (57%) adults completed RIF/PZA. One child (9%) and four adults (17%) developed drug-induced hepatitis. Cultural barriers affected care. The adults resisted the biweekly blood draw, believing it would "drain them of energy." RIF/PZA, plus monitoring, was twice as costly as 4 months of rifampin. CONCLUSIONS: RIF/PZA was associated with significant hepatotoxicity, poor completion, and cultural barriers to monitoring, and was more costly than standard therapy. Tuberculosis prevention must address potential clinical, cultural, and economic barriers to completion and monitoring of short-course therapy in immigrants.
Besides the long-term effectiveness of a given compound, safety is a very important feature to consider when developing new compounds for chemotherapy against tuberculosis. Reports of fatal and severe liver injury associated with rifampicin-pyrazinamide (RIF-PZA) treatment regimens for latent tuberculosis infections prompted this study to evaluate whether a mouse model has any potential as a tool to assess liver injury following extensive exposure to tuberculosis drugs. Mice were administered high doses of existing drug regimens for latent tuberculosis over a relatively short time period. Alanine aminotransferase (ALT), aspartate aminotransferase and bilirubin levels were determined after 2 weeks and 4 weeks of treatment in serum samples collected from uninfected mice as well as mice infected with Mycobacterium tuberculosis. ALT levels increased significantly after a RIF-PZA treatment regimen for 4 weeks in uninfected mice and after 2 weeks in infected mice. Bilirubin serum levels were also significantly elevated in the M. tuberculosis-infected mice after 4 weeks of RIF-PZA treatment. The data obtained indicate that changes in serum enzyme levels in mice after extensive exposure to tuberculosis drugs could be useful as an initial indicator of drug-related hepatotoxicity.
Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA). The nanoparticles were prepared by cation-induced gelification of alginate and were 235.5 +/- 0 nm in size, with drug encapsulation efficiencies of 70-90% for INH and PZA and 80-90% for RIF. The majority of particles (80.5%) were in the respirable range, with mass median aerodynamic diameter of 1.1 +/- 0.4 microm and geometric standard deviation of 1.71 +/- 0.1 microm. The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with oral free drugs. All drugs were detected in organs (lungs, liver and spleen) above the minimum inhibitory concentration until 15 days post nebulisation, whilst free drugs stayed up to day 1. The chemotherapeutic efficacy of three doses of drug-loaded alginate nanoparticles nebulised 15 days apart was comparable with 45 daily doses of oral free drugs. Thus, inhalable alginate nanoparticles can serve as an ideal carrier for the controlled release of antitubercular drugs.
This study was designed to evaluate the pharmacokinetics and tissue distribution of free and alginate-encapsulated antitubercular drugs in mice at different doses. Alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) were prepared by controlled cation-induced gelification of alginate. The formulation was orally administered to mice at two dose levels (D1 and D2). A comparison was made in mice receiving free drugs at equivalent doses. Drugs were analysed by high performance liquid chromatography (HPLC). The average size of alginate nanoparticles was found to be 235.5+/-0.0 nm with a polydispersity index of 0.44; drug encapsulation was 70-90% for INH and PZA, 80-90% for RIF and 88-95% for EMB. In the free drug groups, plasma levels of RIF and INH were higher and PZA and EMB levels were lower in the D1 group (per body surface area of mice) compared with the D2 group (recommended human dose). The plasma drug levels of all drugs were higher in the D1 encapsulated group compared with D2, resulting in higher values of area under the plasma drug concentration-time curve (AUC(0-infinity)). The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with free drugs. Drug levels were maintained at or above the minimum inhibitory concentration (MIC(90)) until Day 15 in organs after administration of encapsulated drugs, whilst free drugs stayed at or above the MIC(90) up to Day 1 only irrespective of dose. The levels of drugs in various organs remained above the MIC at both doses for equal periods, demonstrating their equiefficiency. Alginate nanoparticles hold great potential in reducing dosing frequency of antitubercular drugs.