Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

SETTING: Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure. OBJECTIVE: To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations. DESIGN: Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded. RESULTS: Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001). CONCLUSION: Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.     

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.     

High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002.

BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture-positive pulmonary TB patients registered in 2002. New patients were those treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH], rifampin [RMP], ethambutol, or streptomycin); previously treated patients were those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international reference laboratory, 27 (51%, 95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin, and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania has implemented the WHO global TB control strategy (DOTS), and is developing an MDR-TB treatment program (DOTS-Plus).     

Prevalence of katG Ser315 substitution and rpoB mutations in isoniazid-resistant Mycobacterium tuberculosis isolates from Brazil.

SETTING: Four hundred and sixty-eight isoniazid (INH) resistant Mycobacterium tuberculosis isolates recovered from a selected Brazilian population. OBJECTIVE: To check for susceptibility to other chemotherapeutic drugs used in TB treatment, and to ascertain mutations involved in INH and rifampicin (RMP) resistance. DESIGN: Antimicrobial susceptibility to RMP, streptomycin and ethambutol (EMB) was evaluated by the resistance ratio method and pyrazinamide (PZA) by activity assay. Single strand conformation polymorphism (SSCP) and sequence analysis were performed in samples from this panel to confirm mutations in codon 315 of the katG and in a 69-bp region of the rpoB gene. RESULTS: Combined resistance to INH+RMP, INH+ PZA, INH+EMB, and INH+RMP+PZA was shown in respectively 272 (58.1%), 126 (26.9%), 47 (10%), 116 (24.8%) isolates. No katG mutation was found in 19 (39.6%) of 48 strains tested. Ser315Thr substitution was found in 29 (60.4%). All RMP-resistant strains tested (n = 25) showed rpoB mutations. S531L substitution was found in 15 (60%). CONCLUSION: INH-resistant strains isolated from selected Brazilian populations frequently show resistance to other first-line anti-tuberculosis drugs. rpoB mutation was responsible for RMP resistance in all strains. Among INHr strains, katG mutations were shown in only 60.4%. Genetic approaches targeting the rpoB gene but not the katG gene have a high sensitivity to detect resistance among Brazilian M. tuberculosis strains.     

Anti-tuberculosis drug susceptibility testing of Mycobacterium bovis BCG Tokyo strain.

SETTING: The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine is the only vaccine against tuberculosis (TB), owing to its valuable protective effects and low virulence. However, it can occasionally cause systemic infection in immunocompromised hosts. Isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB) are known to be effective anti-tuberculosis drugs and are used for the treatment of BCG infections. Unfortunately, there are few studies of the susceptibility of BCG vaccine strains to these drugs. OBJECTIVE: To measure the minimum inhibitory concentrations (MICs) of BCG Tokyo vaccine products for anti-tuberculosis drugs and assess vaccine safety in terms of drug susceptibility. DESIGN: We measured the MIC for one seed and five product lots of BCG Tokyo strain for INH, RMP, SM and EMB using Middlebrook 7H11 agar plates. RESULTS: The MIC results for INH were 0.06 and 0.125 mg/ml for the product and seed lots, respectively. The MIC results for RMP, SM and EMB were 0.25-0.5, 0.25 and 2-4 microg/ml, respectively. CONCLUSION: Our results indicate that the BCG Tokyo strain was susceptible to the major anti-tuberculosis drugs and treatable even in cases of severe adverse events, including systemic infection.     

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.     

Rifampicin mono-resistant Mycobacterium tuberculosis in Bujumbura, Burundi: results of a drug resistance survey.

SETTING: Bujumbura, Burundi. OBJECTIVES: To determine resistance levels of Mycobacterium tuberculosis (TB) to the main anti-tuberculosis drugs after 11 years of a DOTS programme using a WHO-recommended partially intermittent 6-month rifampicin (RMP) first-line regimen and fixed-dose drug combinations (FDCs). DESIGN: Drug susceptibility testing of systematic samples of M. tuberculosis isolated from newly registered sputum smear-positive cases in the capital during a 15-month period (2002-2003). RESULTS: Of 496 strains from new cases, 16.1% showed resistance to any drug, 6.3% to isoniazid (INH), 2.0% to RMP (1.4% multidrug-resistant TB [MDR-TB]), 13.3% to streptomycin and 1.6% to ethambutol. Among 69 strains from previously treated cases, the prevalence of resistance was 30%, 19%, 15% (12% MDR-TB strains), 25% and 6%, respectively. CONCLUSION: Levels of drug resistance in Bujumbura are higher than average for Africa, despite long-term use of the DOTS strategy with FDCs and a ban on sales of TB drugs. Most worrying is the appearance of MDR-TB and RMP-resistant, INH-susceptible strains in new cases. Although a survey cannot prove that high HIV prevalence, elevated levels of resistance to some other drugs and irregular intake allowed acquisition of drug resistance, the effectiveness and safety of 6-month regimens with (partially) intermittent RMP throughout under such conditions should be investigated.     

Trend of anti-tuberculosis drug resistance in Korea, 1994-2004.

SETTING: The 245 health centres through which the National Tuberculosis Programme (NTP) is implemented in Korea and the TB Laboratory Network of the Korean National Tuberculosis Association. OBJECTIVE: To observe the trend of anti-tuberculosis drug resistance in Korea from 1994 to 2004 and possible related factors. DESIGN: All tuberculosis (TB) patients registered for treatment at the health centres for a given period were assessed. RESULTS: Of 2636 new smear-positive patients from the 2004 survey, 338 cases (12.8%, 95% confidence interval [CI] 11.5-14.1) showed resistance to any of the first-line drugs: 261 with isoniazid (INH) resistance (9.9%, 95%CI 8.8-11.0) and 71 with multidrug resistance (MDR) (2.7%, 95%CI 2.1-3.3). Compared with previous surveys, a statistically significant increase in MDR (P=0.00675), any drug resistance (P=0.03779), any INH resistance (P=0.00313) and any rifampicin resistance (P = 0.00176) has been observed among new cases since 1994. Any resistance to second-line drugs ranged from 0.1% (capreomycin) to 1.1% (para-aminosalicylic acid) among new cases and from 1.1% to 3.6% among retreatment cases. Resistance to kanamycin and ofloxacin was found in 1.4% and 2.6%, respectively, of new and previously treated MDR-TB cases. CONCLUSION: A statistically significant increase in drug resistance was noticed among new cases.     

The clearance of theophylline is increased during the initial period of tuberculosis treatment.

OBJECTIVE: To evaluate the effects of combined anti-tuberculosis treatment including isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA), on the pharmacokinetics of theophylline during the initial phase of treatment. DESIGN: Prospective, controlled clinical study. PATIENTS AND METHODS: Twenty patients with pulmonary tuberculosis received 7.35 mg/kg/day of aminophylline intravenously combined with anti-tuberculosis agents. The first theophylline serum concentration was measured before administration of INH, RMP, EMB and PZA, and samples were obtained once daily for 6 consecutive days after initiation of treatment. All patients in this study were non-smokers with normal hepatic and renal function, and they were not given any other drugs that could affect the clearance of theophylline. RESULTS: The concentration and half-life of theophylline was decreased and its clearance was increased significantly at days 5-7 after administration of antituberculosis agents compared to before the therapy was started. CONCLUSIONS: These results suggest that patients with asthma or chronic obstructive pulmonary disease administered combinations of anti-tuberculosis agents and theophylline during the initial phase of tuberculosis treatment should be monitored closely for changes in theophylline concentration, and that the dose of theophylline should be adjusted accordingly.     

Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs.

OBJECTIVE: A multicentre evaluation was performed to assess two rapid low-cost methods, MTT (3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) and resazurin assays, for testing the susceptibility of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and streptomycin (SM). METHODS: Thirty coded M. tuberculosis strains were sent to seven laboratories located in Latin America, representing six countries. Each site performed the colorimetric assays, MTT and resazurin, blind for the first-line drugs RMP, INH, EMB and SM. The minimum inhibitory concentration results obtained were compared to the conventional proportion method on Lowenstein-Jensen medium. RESULTS: After establishing the breakpoint concentrations, excellent results were obtained for RMP, INH and EMB, with levels of specificity and sensitivity of between 96% and 99%. CONCLUSION: MTT and resazurin assays are promising, accessible new alternative methods for middle- and low-resource countries that need low-cost methods to perform rapid susceptibility testing of M. tuberculosis to key anti-tuberculosis drugs.     

Tuberkulose im Kindesalter

The prevention, diagnosis and treatment of childhood tuberculosis (TB) remain a challenge. As a result of an increased risk of disease progression after infection in children <?5 years of age, prophylactic treatment with isoniazide (INH) for 3 months is indicated after contact with infected TB patients. For patients with (asymptomatic) latent TB, treatment with INH for 9 months or INH and rifampicine (RMP) for 3 months is indicated for all children and adolescents. Uncomplicated active TB in children can most commonly be treated with a combination of RMP, INH and pyrazinamide (PZA) during the first 2 months followed by a combination of RMP and PZA for the following 4 months. Especially in young children, rapid diagnosis and treatment is crucial because of an increased risk of disseminated life-threatening tuberculosis. The worldwide increase in drug-resistant TB is challenging and children and adolescents should be managed out in specialist centers.     

Improvements in treatment success rates with directly observed therapy in Rio de Janeiro City.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To evaluate the effect of directly observed therapy (DOT) on treatment success, by comparing the treatment success rates between patients treated under DOT with those who received self-administered therapy (SAT). DESIGN: A longitudinal study in a cohort of tuberculosis (TB) patients. Of 9929 new pulmonary TB cases, 1190 (12%) were treated under DOT and 8739 (88%) under SAT. All patients received a three-drug regimen consisting of rifampicin (RMP), isoniazid (INH) and pyrazinamide for 2 months followed by 4 months of RMP and INH. RESULTS: Patients under DOT were more likely to convert to sputum-negative at the end of the second month than those treated under SAT (86.3% vs. 61.9%, P < 0.001). DOT alone was significantly associated with successful treatment (OR 1.6, 95%CI 1.37-1.86, P < 0.001), even when controlled by sex, age and positive smear or culture at enrollment (OR 1.56, 95%CI 1.33-1.82, P < 0.001). CONCLUSION: This pilot DOTS implementation phase showed that DOT is highly effective and feasible in a large urban centre of a developing country.     

Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis

Patient non-compliance is the major drawback associated with the long-duration chemotherapy of tuberculosis (TB); hence, reduction in dosing frequency forms an important therapeutic strategy. The present study reports the formulation of three frontline antitubercular drugs (ATD), i.e. rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) encapsulated in poly (DL-lactide-co-glycolide) (PLG) nanoparticles. Drug encapsulation efficiencies were 56.9+/-2.7% for RIF, 66.3+/-5.8% for INH and 68+/-5.6% for PZA. Following a single oral administration of these preparations to mice, the drugs could be detected in the circulation for 6 days (RIF) and 9 days (INH/PZA), whereas therapeutic concentrations in the tissues were maintained for 9-11 days. Further, on oral administration of drug-loaded nanoparticles to Mycobacterium tuberculosis-infected mice at every 10th day, no tubercle bacilli could be detected in the tissues after 5 oral doses of treatment. Therefore, nanoparticle-based ATD therapy forms a sound basis for reduction in dosing frequency for better management of TB.     

Deteriorated tuberculosis drugs and management system problems in lower southern Thailand.

SETTINGS: Three institutes, 11 hospitals and 38 community hospitals in southern Thailand. OBJECTIVES: To assess the quality of tuberculosis (TB) drugs used in TB treatment facilities in southern Thailand and their TB drug management systems. DESIGN: Cross-sectional study utilising interviews, document review, inspection of drug storage, visual examination of TB drugs, and laboratory analysis of samples of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB). RESULTS: No stock-out of TB drugs was found at any level. Thirteen (25%) hospitals/institutes removed coated EMB tablets from their foil packages for daily dose packing. Eleven (21%) hospitals/institutes bisected 400 mg coated EMB tablets before dispensing as a non-available 200 mg tablet. On the day of inspection grossly deteriorated EMB was observed in 44% of hospitals/institutes. All samples, except 14% of EMB, passed content assay tests. All INH and EMB samples passed the dissolution tests, but 62% of RMP samples and 26% of PZA samples failed. CONCLUSIONS: Sub-standard deteriorated TB drugs are a serious problem for TB control. TB drugs examined in the study area were not managed properly. Education on TB drug packaging and storage, and non-destructive systems in TB drug distribution, storage, inventory control, quality assurance and supervision are essential interventions.     

Impact of country of origin on drug-resistant tuberculosis among foreign-born persons in British Columbia.

SETTING: Provincial tuberculosis (TB) services, British Columbia, Canada. OBJECTIVES: To estimate the risk of drug resistance among foreign-born TB patients and to identify risk factors associated with drug resistance. DESIGN: Using the provincial TB database, we examined all culture-positive foreign-born TB patients for the years 1990-2001. The risk of having a drug-resistant isolate was estimated according to country and region of origin. RESULTS: Of 1940 foreign-born patients identified, 247 (12.7%, 95%CI 11.3-14.3) cases had isolates resistant to at least one of the first-line drugs, with 160 (8.3%) isolates showing monoresistance, 24 (1.2%) multidrug resistance (resistance to at least isoniazid and rifampin) and 63 (3.3%) polyresistance (resistance to two or more drugs, excluding MDR). Country-specific analysis showed that immigrants from Vietnam (adjusted OR 2.12, 95%CI 1.37-3.27) and the Philippines (adjusted OR 1.71, 95%CI 1.10-2.66) had a significantly higher risk of resistance than other immigrants. In addition, the risk was the highest for younger TB patients and patients with reactivated disease (adjusted OR 2.12, 95%CI 1.09-4.09). CONCLUSION: The risk of drug resistance was the highest among foreign-born patients from Vietnam and the Philippines. These findings should assist clinicians in prescribing and tailoring anti-tuberculosis regimens for immigrants more appropriately.     

The physical and chemical stability of anti-tuberculosis fixed-dose combination products under accelerated climatic conditions.

OBJECTIVE: To determine the physical and chemical stability of anti-tuberculosis fixed-dose combinations (FDC) of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) sold on the Indian market. METHODS: The products were stored for 3 months under ICH/WHO accelerated conditions (40 degrees C / 75% RH), with and without the original packaging in the presence and absence of light. RESULTS: The initial RMP, INH and PZA content was found to be within the range of 90-110% of the label claim. However, the products were found to have some chemical instability even initially; one of the tablets also showed physical instability. Under accelerated conditions, the unpackaged products underwent severe changes, whereas both physical and chemical changes were also observed in the packaged formulations. The physical changes were stronger under lighted conditions. A significant finding is that PZA and perhaps EMB may play a catalytic role in the interaction between INH and RMP. CONCLUSION: This study suggests that, unless they are packed in barrier packaging, anti-tuberculosis FDC formulations should be considered unstable, and due consideration should be given to their development pharmaceutics, packaging and stability testing.     

Pattern of mycobacterial resistance to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the state of Qatar after the implementation of DOTS and a limited expatriate screening programme.

OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the State of Qatar after the implementation of DOTS and an expatriate screening programme on arrival. METHOD: A state-wide, population-based, retrospective analysis of all cases of pulmonary tuberculosis with positive M. tuberculosis culture reported to the Division of Public Health TB Unit from January 1996 to December 1998. M. tuberculosis sensitivity testing was done by the Bactec method for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). The results were interpreted as a daily change of the growth index of test vials (with drug) compared with controls. RESULTS: There were 406 isolates with positive M. tuberculosis culture. Sixty-one (15%) were resistant to one or more of the four anti-tuberculosis drugs, of which 58 (95%) were from newly diagnosed cases (primary) and three (5%) were from previously treated cases (acquired). Primary resistance was as follows: any resistance 15%, INH 12.4%, RMP 2%, SM 5.2%, EMB 0.8% and multidrug resistance (MDR, resistance to INH and RMP at least) was found in 0.8%. Acquired resistance was as follows: any resistance 15%, INH 15%, RMP 5%, SM 5% and MDR 5%. CONCLUSION: The prevalence of resistance to four anti-tuberculosis drugs is strikingly low due to the limited expatriate screening programme (chest radiography) and implementation of DOTS. The four-drug regimen is recommended for the initial phase of therapy until the results of sensitivity testing are known.     

Nationwide survey on the prevalence of anti-tuberculosis drug resistance in the Republic of Yemen, 2004.

OBJECTIVES: To determine the prevalence of resistance to the four major anti-tuberculosis drugs, isoniazid, rifampicin, streptomycin and ethambutol, in Yemen. METHODS: Cluster sampling with probability proportionate to size was applied. Susceptibility to four major anti-tuberculosis drugs was examined. The proportion method using L?wenstein-Jensen medium or Ogawa medium was carried out. RESULTS: A total of 790 primary culture isolates from tuberculosis (TB) cases enrolled at the National Tuberculosis Institute, Yemen, were examined. In the confirmation culture at the supranational reference laboratory, 227 of them failed to grow on the secondary culture or were proved to be mycobacteria other than Mycobacterium tuberculosis and were excluded from further analysis. Among 563 cultures, 510 were obtained from new cases and 53 from previously treated cases. The prevalence of resistance to any four drugs was 9.8% (95%CI 7.0-12.5) among new cases and 17.4% (95%CI 12.0-33.5) among previously treated cases. The prevalence of multidrug-resistant TB was 3.0% (95%CI 1.5-4.5) among new cases and 9.4% (95%CI 0.2-18.7) among previously treated cases. CONCLUSION: The first nationwide prevalence survey on resistance to the four major anti-tuberculosis drugs in Yemen showed a relatively low prevalence of drug-resistant cases, but a high prevalence of multidrug resistance among new cases.     

Defaulting from anti-tuberculosis treatment in a teaching hospital in Rio de Janeiro, Brazil.

SETTING: Few studies have investigated factors associated with defaulting from anti-tuberculosis (TB) therapy in hospital settings. OBJECTIVE: To identify the factors associated with defaulting from treatment among TB in-patients in Rio de Janeiro city, Brazil. DESIGN: Case-control study. METHODS: All study participants initiated anti-tuberculosis treatment in a teaching hospital. A defaulting case was defined as a person who did not return for anti-tuberculosis medications after 60 days. Cases and controls were interviewed by a trained health care worker using a standardized form. RESULTS: From 1 January to 31 December 1997, 228 TB cases were registered. After a review of the medical records, 39 were excluded. Household visits were performed in 189 patients; 46 subjects were identified as cases and 117 as controls. Defaulting from anti-tuberculosis treatment was observed in 66 cases (28.9%) before and in 46 (20.2%) after a home visit. After multivariate analysis, the strongest predictors of defaulting from treatment were: 1) returning card not provided (OR 0.099; 95%CI 0.008-1.2; P = 0.07), 2) not feeling comfortable with a doctor (OR 0.16; 95%CI 0.33-0.015; P = 0.001), and 3) blood pressure not measured (OR 0.072; 95%CI 0.036-0.79; P = 0.024). CONCLUSIONS: In this hospital, the factors associated with defaulting from anti-tuberculosis treatment highlight the necessity for a structured TB Control Program. It is expected that the implementation of such a program, pursuing specific approaches, should enhance completion of anti-tuberculosis treatment and cure.