trifazid and Tuberculosis--Pulmonary

Shorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and regimens, other modalities like host-directed therapy are also being suggested to reach this goal. This study's objective is to assess the efficacy and safety of metformin-containing anti-TB treatment (ATT) regimen in comparison to the standard 6-month ATT regimen in the treatment of patients with newly diagnosed sputum smear-positive drug-sensitive pulmonary TB.. We are conducting a multicentric, randomised open-label controlled clinical trial to achieve the study objective. The intervention group will receive isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) along with 1000 mg of daily metformin (Met) for the first 2 months while the control group will receive only HRZE. After 2 months, both the groups will receive HRE daily for 4 months. The primary endpoint is time to sputum culture conversion. Secondary endpoints will include time to detection of. The ethics committee of the participating institutes have approved the study. Results from this trial will contribute to evidence towards constructing a shorter, effective and safe regimen for patients with TB. The results will be shared widely with the National Programme managers, policymakers and stakeholders through open access publications, dissemination meetings, conference abstracts and policy briefs. This is expected to provide a new standard of care for drug-sensitive patients with pulmonary TB who will not only reduce the number of clinic visits and lost to follow-up of patients from treatment but also reduce the burden on the healthcare system.. CTRI/2018/01/011176; Pre-results.

Topics: Adult; Antibiotics, Antitubercular; Drug Combinations; Drug Therapy, Combination; Ethambutol; Humans; India; Isoniazid; Metformin; Multicenter Studies as Topic; Mycobacterium tuberculosis; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Tuberculosis, Pulmonary

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients.. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART).. A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported.. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Topics: Adenine; Adult; Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Cyclopropanes; Deoxycytidine; Drug Combinations; Drug Therapy, Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Ethambutol; Female; HIV Infections; Humans; Isoniazid; Male; Organophosphonates; Oxazines; Pyrazinamide; Reverse Transcriptase Inhibitors; Rifampin; Treatment Outcome; Tuberculosis, Pulmonary

Veterans General Hospital-Taipei, Taiwan.. To assess the efficacy and safety of a fixed-dose combination (FDC) of Rifater (RFT)/Rifinah (RFN) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis.. Patients were randomly assigned to two 6-month short-course chemotherapy regimens. One group of patients was treated with FDCs and another was given the four component drugs (INH, RMP, EMB and PZA) as separate formulations.. The 105 patients enrolled in the study were divided into two treatment groups. Fifty-one patients who had completed treatment without interruption, 26 in the FDC group and 25 in the separate regimen, were eligible for analysis at the end of 2 years. Among the patients with a drug susceptibility test result available, four in the FDC group had bacilli resistant to pyrazinamide. In the separate regimen group, two patients had bacilli resistant to ethambutol and six had bacilli resistant to pyrazinamide. The two regimens were of similar effectiveness with regard to sputum conversion, compliance and radiological improvement. No patient with FDC treatment developed gastointestinal symptoms, visual disturbance or peripheral neuropathy (P < 0.05). However, FDC treatment resulted in drug-induced fever in one patient. One patient (3.8%) in the FDC group relapsed 5 months after completing treatment.. This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis. However, the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile.

Topics: Adult; Antitubercular Agents; Drug Combinations; Female; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Patient Compliance; Pyrazinamide; Rifampin; Sputum; Taiwan; Tuberculosis, Pulmonary

Singapore Tuberculosis Service.. To assess the acceptability, efficacy and relapse rate of a combined formulation of three drugs--isoniazid, rifampicin and pyrazinamide (Rifater)--given in the initial phase of chemotherapy in three 6-month regimens (2SHRZ/4H3R3, 1SHRZ/5H3R3 and 2HRZ/4H3R3) under direct observation for all patients.. A randomised, controlled, unblinded study comparing a group of patients treated with Rifater and another given the three component drugs as separate formulations.. The 310 patients admitted to the study were divided into two groups of 155 patients. The frequency of side effects was similar in both groups. Of 271 patients with drug-sensitive strains who had completed treatment without interruption, sputum cultures converted in all patients. At the end of 5 years, there were 15 relapses: three (2.2%) in the separate drugs group and 12 (9.3%) in the Rifater group. Exclusion of two cases in the Rifater group, one with silicotuberculosis and another with no bacteriological confirmation of diagnosis, gave a relapse rate of 7.9% (P = 0.03 for the comparison of relapse rates in the two groups).. A combined formulation of three drugs given daily in the initial phase of 6-month short-course therapy, followed by intermittent treatment with isoniazid and rifampicin given three times a week under direct observation for all patients, appears to be less effective than treatment with the component drugs given as separate formulations.

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Combinations; Follow-Up Studies; Humans; Isoniazid; Pyrazinamide; Recurrence; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Tuberculosis is still a major public health threat in Thailand. The introduction of a short course of chemotherapy at national level might help reduce the magnitude of the problem. In order to assess the efficacy and toleration of two different regimens of chemotherapy under field conditions, a comparative clinically controlled trial was conducted at the Central Chest Hospital in Nonthaburi, Thailand. From January 1988 to August 1990, 199, newly diagnosed, untreated, sputum positive tuberculosis patients were allocated randomly to two treatment groups; in Group A, 97 patients received Rifater daily for the first 2 months, followed by Rifinah daily for 4 months (2 Rifater/4 Rifinah). In Group B, 102 patients received Rifater supplemented by ethambutol daily for the first 2 months followed by thiacetazone and isoniazid daily for 6 months (2 Rifater EMB/6 HT.) Treatment results were very satisfactory in both groups. At the end of treatment conversion rates were 100 per cent in Group A, and 99 per cent in Group B. After a period of 36 months following completion of treatment, relapse rates of 3 per cent for Group A and 4 per cent for Group B were observed. Adverse reactions were minimal in both groups, but acne formation and gastrointestinal symptoms were noticed more in Group B, suggestive of thiacetazone side effects. This study shows that, the 6-months regimen is as effective as the 8-months regimen. Although the 8-months regimen is cheaper, it causes more gastrointestinal disturbance and skin reaction which might led to less patient compliance and result in a lower cure rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antitubercular Agents; Drug Combinations; Female; Follow-Up Studies; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Retrospective Studies; Rifampin; Thailand; Treatment Outcome; Tuberculosis, Pulmonary

In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Drug Administration Schedule; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Pyrazinamide; Recurrence; Rifampin; Sputum; Streptomycin; Tuberculosis, Pulmonary

In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at random to daily chemotherapy with streptomycin, isoniazid, rifampin, and pyrazinamide (1) for 2 months (2SHRZ), (2) for 1 month (1SHRZ), or (3) for 2 months without streptomycin (2HRZ). This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months. During the initial period of daily chemotherapy the patients were also allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide, or as three separate drugs. During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting, reported by 8% of 155 patients receiving Rifater and 7% of 155 separate drugs. Other adverse effects were also reported in similar proportions in the two series. Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy. During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 (7%) of 46 2SHRZ, 2 (5%) of 42 1SHRZ, and 3 (8%) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ, 1 (2%) of 46 1SHRZ, and 1 (2%) of 44 2HRZ patients allocated to separate drugs. There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ. The relapse rates were slightly higher in the Rifater series (p = 0.04). Further follow-up and results from other studies are therefore needed fully to assess the combined preparation.

Topics: Adolescent; Adult; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Patient Compliance; Pyrazinamide; Recurrence; Rifampin; Sputum; Streptomycin; Tuberculosis, Pulmonary

The effectiveness of a tablet containing a combination of rifampicin, isoniazid and pyrazinamide (Rifater; Mer-National) in the treatment of pulmonary tuberculosis was examined by comparing it with a previously evaluated four-drug regimen. Of 150 black goldminers with a first case of pulmonary tuberculosis, 69 were randomly allocated to receive the combination tablet (RHZ), 5 tablets per day on weekdays for 100 treatment-days, and 81 the four-drug regimen (streptomycin, rifampicin, isoniazid and pyrazinamide) (RHZS). Non-compliance was detected in 42% of the RHZ group and in 16% of the RHZS group. Two patients in the RHZ group and 4 in the RHZS group had to have their treatment altered because routine investigations revealed drug-resistant mycobacteria. Treatment was unsuccessful in 10 patients in the RHZ group, with 4 men failing to complete the regimen and being lost to follow-up, 3 cases of failure of conversion of sputum on the regimen, and 3 relapses. The results for the RHZS group were similar, with 4 failures to complete the regimen, 2 treatment failures and 4 relapses. Evaluation of RHZ showed it to be comparable with a previously evaluated, successful short-course regimen (RHZS). The high incidence of non-compliance probably reflects reduced supervision of this wholly oral regimen.

Topics: Adult; Antitubercular Agents; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Streptomycin; Tablets; Tuberculosis, Pulmonary

Treatment of tuberculosis should be as short and as simple as possible in order to improve patient compliance; and combinations of at least three drugs should be used in order to kill the different populations of mycobacteria and to avoid development of drug resistance.--In a controlled multicentre study two regimens were compared in 93 patients with newly-diagnosed pulmonary tuberculosis: 1) Six-month therapy (47 cases): Daily rifampicin and isoniazid, supplemented with pyrazinamide for the first 2 months. A tablet with a fixed combination of 120 mg rifampicin, 50 mg isoniazid and 300 mg pyrazinamide (Rifater) was used. 2) Present Swiss standard therapy (46 cases): Daily rifampicin, isoniazid and ethambutol for 2 months followed by rifampicin and isoniazid for 7 months.--The time-course of culture negativation and the frequency of adverse events were similar in the two groups. During a follow-up period of at least two years only one relapse was observed in the six-month regimen, 3 months after completion of treatment. This was one of three patients with pretreatment resistance to isoniazid. Nevertheless, two of them were cured with the six-month regimen containing Rifater.--Patient compliance, assessed during outpatient treatment by detecting isoniazid metabolites in the urine, was very good (93% of tests were positive in each group).--These results with a follow-up of more than 2 years, indicate that short-course therapy of 6 months duration with the fixed combination tablet may be recommended as treatment of choice in pulmonary tuberculosis except in cases of isoniazid resistance and other special situations (i.e. large cavitations, large number of viable bacilli).

Topics: Adult; Antitubercular Agents; Drug Combinations; Ethambutol; Female; Humans; Isoniazid; Male; Middle Aged; Multicenter Studies as Topic; Patient Compliance; Prospective Studies; Pyrazinamide; Recurrence; Rifampin; Time Factors; Tuberculosis, Pulmonary

Effective treatment of Mycobacterium tuberculosis (Mtb) infection requires at least 6 months of daily therapy with multiple orally administered antibiotics. Although this drug regimen is administered annually to millions worldwide, the impact of such intensive antimicrobial treatment on the host microbiome has never been formally investigated. Here, we characterized the longitudinal outcome of conventional isoniazid-rifampin-pyrazinamide (HRZ) TB drug administration on the diversity and composition of the intestinal microbiota in Mtb-infected mice by means of 16S rRNA sequencing. We also investigated the effects of each of the individual antibiotics alone and in different combinations.. While inducing only a transient decrease in microbial diversity, HRZ treatment triggered a marked, immediate and reproducible alteration in community structure that persisted for the entire course of therapy and for at least 3 months following its cessation. Members of order Clostridiales were among the taxa that decreased in relative frequencies during treatment and family Porphyromonadaceae significantly increased post treatment. Experiments comparing monotherapy and different combination therapies identified rifampin as the major driver of the observed alterations induced by the HRZ cocktail but also revealed unexpected effects of isoniazid and pyrazinamide in certain drug pairings.. This report provides the first detailed analysis of the longitudinal changes in the intestinal microbiota due to anti-tuberculosis therapy. Importantly, many of the affected taxa have been previously shown in other systems to be associated with modifications in immunologic function. Together, our findings reveal that the antibiotics used in conventional TB treatment induce a distinct and long lasting dysbiosis. In addition, they establish a murine model for studying the potential impact of this dysbiosis on host resistance and physiology.

Topics: Animals; Antitubercular Agents; Clostridiales; Drug Combinations; Dysbiosis; Gastrointestinal Microbiome; Intestines; Isoniazid; Mice; Mycobacterium tuberculosis; Porphyromonas; Pyrazinamide; Rifampin; RNA, Ribosomal, 16S; Tuberculosis, Pulmonary

Rosacea is a common chronic inflammatory cutaneous disease of unknown etiology, characterized by remissions and exacerbations, presenting with centrofacial erythema and telangiectasias. It affects mainly adults around the age of 30 years and classically predominates in females. The pathophysiology of rosacea has not yet been fully understood. Risk factors are positive family history, very light skin phototype, sun exposure and consumption of spicy food or alcohol. Recently, there has been some evidence that some drugs or vitamins could be potential factors that can aggravate rosacea or induce rosacea-like symptoms. In this context, we present a 53-year-old female developing rosacea-like dermatitis due to a fixed combination of isoniazid and pyridoxine, which she was receiving along with rifampicin for the treatment of pulmonary tuberculosis.

Topics: Antitubercular Agents; Drug Combinations; Drug Eruptions; Female; Humans; Isoniazid; Middle Aged; Pyrazinamide; Pyridoxine; Rifampin; Rosacea; Tuberculosis, Pulmonary; Vitamin B Complex

Topics: Antitubercular Agents; Drug Combinations; Humans; Isoniazid; Male; Middle Aged; Olfaction Disorders; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Antitubercular Agents; Drug Combinations; Drug Eruptions; Drug Therapy, Combination; Dysgeusia; Flushing; Histamine H1 Antagonists; Humans; Isoniazid; Loratadine; Male; Pruritus; Pyrazinamide; Recurrence; Rifampin; Tryptases; Tuberculosis, Pulmonary; Vasodilation

Pulmonary tuberculosis can be associated with skin manifestations. We report a case in which cutaneous tuberculous lesions were associated with asymptomatic pulmonary tuberculosis. A 15-year old woman had four cutaneous tumoral lesions on her face back, a few of which had evolved over a period of several years. They were asymptomatic nodular lesions, with rounded bumps, with, in places, cheloidal features. The biopsy specimen revealed non-caseating epithelioid granulomas with giant cells and the culture grew Mycobacterium tuberculosis. Cavitating pulmonary tuberculosis was then revealed by CT scan and acid-fast bacilli were isolated in her sputum. The skin lesions disappeared with anti-tuberculosis therapy. Cutaneous manifestations of tuberculosis are rare, polymorphous, and can be associated with an underlying visceral infection. Lupus vulgaris is the most common cutaneous manifestation of tuberculosis in industrialised countries, but nevertheless it remains rare and it is a very unusual presenting feature of underlying pulmonary tuberculosis.

Topics: Adolescent; Antitubercular Agents; Biopsy; Drug Combinations; Female; Humans; Isoniazid; Lupus Vulgaris; Luxembourg; Philippines; Pyrazinamide; Rifampin; Sputum; Tomography, X-Ray Computed; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Combinations; Humans; Isoniazid; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

The early bactericidal activity (EBA) of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater: Mer National) was evaluated in patients with pulmonary tuberculosis who were sputum-positive on microscopy for acid-fast bacilli. Twenty-eight patients (mean age 33 years and weight 51 kg on average; range 40-59 kg) were studied. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days following the start of treatment was estimated from counts of colony-forming units (CFUs) of M. tuberculosis per ml of sputum cultured on selective 7H10 agar medium. The EBA for ethambutol determined in 9 patients was 0.245 +/- 0.046, log10 CFU/ml sputum/day, that for pyrazinamide was 0.003 +/- 0.014 log10 CFU/ml sputum/day and that for Rifater 0.558 +/- 0.054 log10 CFU/ml sputum/day. The results obtained are similar to those reported in a previous study of the first 2 days of treatment, but in smaller numbers of patients, and confirm the moderate EBA of ethambutol while pyrazinamide is again shown to have very little EBA. Rifater has a marked EBA which may be due mainly to the action of isoniazid. This methodology may be valuable in the rapid evaluation of the bactericidal activity of new antituberculosis agents and the comparison of different dose sizes of agents of the same class.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Middle Aged; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; South Africa; Sputum; Tuberculosis, Pulmonary

Perforation and obstruction of the small intestine are well recognized in cases of ulcero-constrictive gastro-intestinal tuberculosis and at the commencement of anti-tuberculous chemotherapy. We present a case of two metachronous perforations in a patient despite established anti-tuberculous treatment.

Topics: Adult; Antitubercular Agents; Drug Combinations; Female; Humans; Intestinal Perforation; Isoniazid; Pyrazinamide; Rifampin; Tuberculosis, Gastrointestinal; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Combinations; Ethambutol; Female; Follow-Up Studies; Humans; Isoniazid; Male; Patient Compliance; Pyrazinamide; Recurrence; Rifampin; Tuberculosis, Pulmonary

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.

Topics: Adult; Antitubercular Agents; Cell Division; Chromosome Aberrations; Drug Combinations; Female; Humans; Isoniazid; Lymphocytes; Male; Middle Aged; Mitotic Index; Mutagens; Pyrazinamide; Rifampin; Sister Chromatid Exchange; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Combinations; Humans; Isoniazid; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

In this study two highly effective chemotherapeutic regimens of 6 and 8 months duration were studied and compared with the standard 12 month therapy under full supervision at the National TB Centre and St. Peter's TB Hospital in Addis Abeba. Patients with direct smear positive pulmonary tuberculosis were admitted to hospital during the initial phase of treatment for two months. At two months, sputum conversion rates, by direct smear and culture respectively, were 82% and 80% on Rifater, and 86 or 88% and 86% on the regimens containing separate preparations of isoniazid rifampicin and pyrazinamide, compared to 60% and 30% on the standard regimen. It was concluded that short course regimens of six or eight months with drugs either in combined form or separate preparations are more effective than the standard regimen.

Topics: Adolescent; Adult; Aged; Drug Combinations; Drug Therapy, Combination; Humans; Isoniazid; Middle Aged; Mycobacterium tuberculosis; Patient Compliance; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary