Evaluation of Mycobacterium Avium Complex Pulmonary Disease Treatment Completion and Adherence to ATS/IDSA Guidelines.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that cause infections leading to chronic, debilitating pulmonary disease, among which Mycobacterium avium complex (MAC) is the most common species. METHODS: We described patterns of macrolide-based multidrug antibiotic therapies for MAC pulmonary disease (MAC-PD) in US Medicare beneficiaries with bronchiectasis between January 2006 and December 2014. MAC therapy was defined as a multidrug regimen containing a macrolide plus ≥1 other drug targeting MAC-PD (rifamycin, ethambutol, fluoroquinolone, or amikacin) prescribed concomitantly for >28 days. RESULTS: We identified 9189 new MAC therapy users, with a mean age (standard deviation) of 74 (6 years) at the start of therapy; 75% female and 87% non-Hispanic white. A guideline-based regimen (a macrolide, ethambutol, and rifamycin, with or without amikacin) was prescribed for 51% of new MAC therapy users at treatment start, of whom 41% were continuing guideline-based therapy at 6 months, and only 18% at 12 months. Of all new MAC therapy users, by 18 months only 11% were still receiving MAC treatment, 55% had discontinued therapy, and 34% were censored owing to death or the end of the study period. CONCLUSIONS: Overall, nearly half of new MAC therapy users were prescribed a non-guideline-recommended macrolide-based therapy, including regimens commonly associated with promoting macrolide resistance. Treatment discontinuation was common, and once discontinued, only a few beneficiaries resumed therapy at a later time. Our study adds important data to the current literature on treatment patterns for MAC-PD among older US populations. Future research should examine treatment patterns using more contemporary data sources.

Tuberculosis in 2019.

Tuberculosis (TB) updates and guidelines have been published rapidly in last few years. The WHO and RNTCP have recommended suggestions that have changed the diagnostics and therapeutics paradigm in 2019. The rapid nature of these changes need to be appraised at the pulmonologist end. We conducted a google survey to study these gaps and subsequently review TB in 2019 focusing on the gaps in the survey. We narrate a short review covering the important diagnostic and therapeutic aspects in brief. We discuss the results of our google survey to address the knowledge gaps. Diagnosis, principles and rationale of therapy and treatment of drug sensitive and drug resistant tuberculosis including the shorter regimen and regrouping of drugs are important considerations of our review.

Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomised trial.

BACKGROUND: Active case finding is recommended as an important strategy to control tuberculosis, particularly in low-income and middle-income countries with a high prevalence of the disease. However, the costs and cost-effectiveness of active case finding are unclear due to the absence of evidence from randomised trials. We assessed the costs and cost-effectiveness of an active case finding strategy in Vietnam, where there is a high prevalence of tuberculosis. METHODS: We conducted an economic evaluation alongside the Active Case Finding in Tuberculosis (ACT2) trial-a pragmatic cluster-randomised controlled trial in 70 districts across eight provinces of Vietnam. Patients aged 15 years and older with smear-positive pulmonary tuberculosis were recruited to the trial if they lived with one or more other household members. Household contacts were verbally invited to the clinic by the index patient with tuberculosis. ACT2 compared a combination of active and passive case finding with usual care (passive case finding) of household contacts of patients with tuberculosis from a health system perspective. Clustering occurred at the district and household level. Districts were the unit of randomisation, and we used minimisation to ensure balance of intervention and control districts within each province. In the intervention group, participants were invited to attend screening at baseline, 6 months, 12 months, and 24 months. We determined health-care costs with a standardised national costing survey and reported results in 2017 $US. The primary outcome of our study was disability-adjusted life years (DALYs) averted over a 24-month period. ACT2 was registered prospectively with the Australian and New Zealand Clinical Trials Registry, number ACTRN126.100.00600044. FINDINGS: Between Aug 11, 2010, and Aug 11, 2015, 10 964 index patients and 25 707 household contacts completed the ACT2 study. There were 10 069 household contacts in the intervention group and 15 638 household contacts in the control group. The incremental cost-effectiveness ratio per DALY averted was $544 (330-1375). INTERPRETATION: Active case finding was shown to be highly cost-effective in a setting with a high prevalence of tuberculosis. Investment in the wide-scale implementation of this programme in Vietnam should be strongly supported. FUNDING: Australian National Health and Medical Research Council.

Improving treatment outcome assessment in a mouse tuberculosis model.

Preclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach. BALB/c mice were infected with a Mycobacterium tuberculosis Beijing genotype strain and were treated with rifapentine-pyrazinamide-isoniazid-ethambutol (RpZHE), rifampicin-pyrazinamide-moxifloxacin-ethambutol (RZME) or rifampicin-pyrazinamide-moxifloxacin-isoniazid (RZMH). Treatment outcome was assessed in n = 3 mice after 9 different treatment lengths between 2-6 months. Next, we created a mathematical model that best fitted the observational data and used this for inter-regimen comparison. The observed data were best described by a sigmoidal Emax model in favor over linear or conventional Emax models. Estimating regimen-specific parameters showed significantly higher curative potentials for RZME and RpZHE compared to RZMH. In conclusion, we provide a new design for treatment outcome evaluation in a mouse TB model, which (i) provides accurate tools for assessment of the relationship between treatment length and predicted cure, (ii) allows for efficient comparison between regimens and (iii) adheres to the reduction and refinement principles of laboratory animal use.

Assessment of Bactericidal Drug Activity and Treatment Outcome in a Mouse Tuberculosis Model Using a Clinical Beijing Strain.

Mycobacterium tuberculosis Beijing strains are associated with lower treatment success rates in tuberculosis (TB) patients. In contrast, laboratory strains such as H37Rv are often used in preclinical tuberculosis models. Therefore, we explored the impact of using a clinical Beijing strain on treatment outcome in our mouse tuberculosis model. Additionally, the predictive value of bactericidal activity on treatment outcome was assessed. BALB/c mice were infected with a Beijing strain and treated with one of 10 different combinations of conventional anti-TB drugs. Bactericidal activity was assessed by determining reductions in mycobacterial load after 7, 14, and 28 days and after 2, 3, and 6 months of treatment. Treatment outcome was evaluated after a 6-month treatment course and was based on lung culture status 3 months posttreatment. None of the anti-TB drug regimens tested could achieve 100% treatment success. Treatment outcome depended critically on rifampin. Four non-rifampin-containing regimens showed 0% treatment success compared to success rates between 81 and 95% for six rifampin-containing regimens. Bactericidal activity was predictive only for treatment outcome after 3 months of treatment. Our data advocate the use of multiple mycobacterial strains, including a Beijing strain, to increase the translational value of mouse TB models evaluating treatment outcome. Additionally, our findings support the notion that bactericidal activity in the first 2 months of treatment, as measured in clinical phase IIa/b trials, has limited predictive value for tuberculosis treatment outcome, thus emphasizing the need for better parameters to guide future phase IIII trials.

Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis.

BACKGROUND.: Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. METHODS.: We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. RESULTS.: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. CONCLUSIONS.: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.

Tackling the unknowns of short-course rifapentine-based treatment for active tuberculosis: a decision analysis.

BACKGROUND: Shorter treatment regimens for tuberculosis (TB) are deemed vital for advancing TB control. Murine studies have suggested potential new regimens; however, Phase II human studies of these drug combinations have not shown clear improvement in 2-month culture conversion over current therapy. Nevertheless, drugs such as rifapentine (RPT) may have additional sterilizing effects after 2 months that are difficult to measure in current Phase II studies. OBJECTIVES: To model potential bactericidal effects of RPT in a Phase III trial of a 4-month anti-tuberculosis regimen. METHODS: We developed a Markov model of anti-tuberculosis treatment to compare two regimens for treating TB: a 6-month standard (rifampin-based) treatment and a 4-month regimen using high-dose RPT. The primary outcome was the number of relapses. RESULTS: In the base-case scenario, standard therapy resulted in fewer relapses; improvement in 2-month culture conversion rates in the RPT arm did not change this result. However, while RPT has better sterilizing ability during months 3 and 4 (as observed in the mouse model), the 4-month regimen results in fewer relapses. CONCLUSIONS: Higher 2-month culture conversion rates are neither sufficient nor necessary for making a theoretical 4-month anti-tuberculosis treatment regimen advantageous.

Investigating gender disparities in the profile and treatment outcomes of tuberculosis in Ebonyi state, Nigeria.

SUMMARY Globally, twice as many men as women are being diagnosed with tuberculosis (TB) annually. Little is known about gender differentials in TB in Africa. A retrospective cohort analysis of routine data was conducted on adult TB patients treated between 2011 and 2012 in two large healthcare facilities in Nigeria. Gender differences in their demographic characteristics and treatment outcomes were analysed accordingly. Of 1668 TB patients enrolled, the male:female ratio was 1.4:1. The mean ages of males and females were 40.2 ± 14.7 and 36.1 ± 14.6 years, respectively (t test 6.62, P < 0.001). Male gender was associated with a higher failure to smear convert after 2 months (21.8% vs. 17.5%, P = 0.06) and 5 months (4.3% vs. 1.5%, P = 0.02) of treatment for smear-positive TB patients. Moreover, men were more likely than women to fail treatment (2.2% vs. 0.7%, P = 0.01). No significant differences exist in the treatment success rates between women and men (78.2% vs. 74.5%, P = 0.08). Adjusted analyses showed significant association between being an urban male and a HIV-infected female with unsuccessful outcome adjusted by socio-demographic and clinical factors. We found that gender disparities exist in TB profile and treatment outcomes in Nigeria and gender-specific strategies are needed to optimize TB management.

Prevalence of extended treatment in pulmonary tuberculosis patients receiving first-line therapy and its association with recurrent tuberculosis in Beijing, China.

BACKGROUND: In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB. METHODS: Retrospective cohort study using the electronic national TB information system and dispensary medical records. RESULTS: Of 935 patients with pulmonary TB who completed 6-7 months of first-line drug treatment, 399 (43%) were given extended treatment. This was more common in patients with smear-positive disease, and those with lung cavities and more extensive radiographic lobar involvement at the time of diagnosis. Over 3-4 years' follow-up, recurrent disease was not significantly different in patients who received extended treatment (2.8%, 11/399) as compared to those who received the standard 6-month treatment (3.7%, 20/534). The median length of extended treatment was 89 days at a median cost of US$111 for drugs and US$32 for laboratory examinations. CONCLUSIONS: This study shows that extended treatment is common in one TB dispensary in Beijing. Further studies are needed to determine the countrywide prevalence of this practice and ascertain more conclusively the apparent lack of benefit.

Evaluation of tuberculosis underreporting in Greece through comparison with anti-tuberculosis drug consumption.

Surveillance is an integral part of tuberculosis (TB) control. Greece has a low TB notification rate, but there are doubts about underreporting. Examining anti-TB drug consumption is a way to validate the results of surveillance and estimate TB burden in the country. We used surveillance data from 2004 to 2008 to calculate the average prescribed treatment duration with the first-line anti-TB drugs isoniazid, rifampicin, ethambutol and pyrazinamide. We then obtained the best available data on consumption of these drugs, and calculated the number of treated cases to which these quantities correspond. We thus estimated underreporting at around 80% (77-81%), and annual TB incidence at about 30 cases per 100,000 population, five times over the notification rate. Underreporting was found to be constant over the study period, while incidence followed a decreasing trend. In addition we estimated that one person receives chemoprophylaxis for latent tuberculosis infection (LTBI) for every three TB cases. These results indicate the need for a comprehensive plan to improve TB surveillance and TB contact tracing in Greece, especially in light of the economic crisis affecting the country since 2009.

In-house, simple & economical phage technique for rapid detection of rifampicin, isoniazid, ethambutol, streptomycin & ciprofloxacin drug resistance using Mycobacterium tuberculosis isolates.

BACKGROUND & OBJECTIVES: Multiple drug resistance (MDR) among Mycobacterium tuberculosis poses a serious therapeutic problem. Early detection of MDR can be valuable but the conventional drug susceptibility tests take 4-6 wk time after the laboratory isolation of M. tuberculosis. The bacterial phage assay has been reported as a rapid tool for rifampicin susceptibility testing of tubercle bacilli using the suspension of isolated cultures. The present study was aimed to set up a phage assay for testing drug susceptibility to isoniazid (INH), rifampicin, ethambutol, streptomycin and ciprofloxacin in M. tuberculosis isolates. METHODS: Mueller-Hinton broth instead of Middle Brook 7H9 broth was used to make it more economical. The phage assay was compared with the proportion method using 100 M. tuberculosis isolates from pulmonery TB cases. Phage assay results were available in 48 h for rifampicin and streptomycin while 72 h required for INH, ethambutol and ciprofloxacin. The assay was compared with gold standard proportion method. Interpretation of the results was easy and clear. RESULTS: In the present study, sensitivity and specificity of the phage assay when compared to proportion method were in the range of 97 to 100 per cent for all the drugs except for ciprofloxacin for which it was 93 and 96 per cent, respectively. INTERPRETATION & CONCLUSIONS: The phage assay was economic, easy to perform and rapid for the detection of drug resistance in M. tuberculosis isolates with no requirement of expensive equipment. It is within the reach of microbiology laboratories in developing countries having high loads of tuberculosis.

The cost-effectiveness of tuberculosis preventive therapy for HIV-infected individuals in southern India: a trial-based analysis.

BACKGROUND: Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India. METHODS: We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH). RESULTS: Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence. CONCLUSIONS: Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.

Strategies for treating latent multiple-drug resistant tuberculosis: a decision analysis.

BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice.

Assessment of protective role of polyherbal preparation, Livina, against anti-tubercular drug induced liver dysfunction.

The present study evaluated the possible protective role of Livina (a polyherbal preparation) against anti-tubercular therapy (ATT)-induced liver dysfunction in patients of pulmonary tuberculosis. Patients were given intensive phase treatment with 4-drugs (rifampicin, INH, pyrazinamide and ethambutol) used for anti-tubercular therapy for 2 months, followed by a 4-month continuous phase treatment with 2 drugs (rifampicin and INH) under clinical advice and supervision. Both qualitative and quantitative measures of liver function were assessed, at different time intervals, before and after ATT. Analysis of data showed that the incidence of qualitative manifestations of liver dysfunction were greater in the placebo treated group as compared to the test drug group. None of the patients of either group showed clinical jaundice. Most signific changes ant were observed in the SGOT and SGPT levels in the placebo group, wherein the levels of both enzymes were higher at 4 and 8 weeks post-ATT, as compared to the respective baseline (0 week) values. When Livina (2 capsules twice daily) was given with ATT drugs, incidence of qualitative manifestation of liver dysfunction was insignificant and SGOT and SGPT levels were also significantly lower than the placebo+AITT drugs treated group. These results indicate that the test drug (Livina) was efficacious, against ATT-induced hepatic dysfunction in patients of pulmonary tuberculosis.

Assessment of in vivo antimalarial activity of rifampicin, isoniazide, and ethambutol combination therapy.

The existing armament of drugs for the treatment and prevention of malaria is inadequate due to development of resistance. In addition to this due to lack of economic enticement the rate of new drug development and new drug discovery in the segment of parasitic diseases is very low as compared to the other segments. This has necessitated the better deployment and usage of existing antimalarial drugs as well as discovery of antimalarial activity of drugs which are well characterized for other diseases; these approaches help to reduce the time and cost required for new drug discovery. The present study evaluated the antimalarial activity of antituberculosis drugs rifampicin, isoniazide, and ethambutol in monotherapy and combination in Plasmodium berghei-infected mice. Animals were observed for mortality, parasite progression, and toxicity for a period of 1 month. Rifampicin + isoniazide and rifampicin + isoniazide + ethambutol treatment resulted in an overall survival rate of 60% compared to 0% in vehicle-fed animals by 4 weeks after post-infection without showing any toxicity.

Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy.

BACKGROUND: The mainstays of treatment for pulmonary disease caused by opportunist mycobacteria are rifampicin (R) and ethambutol (E). The role of macrolides, quinolones and immunotherapy with Mycobacterium vaccae is not clear. A trial was undertaken to compare clarithromycin (Clari) and ciprofloxacin (Cipro) as third drugs added to [corrected] 2 years of treatment with R and E for pulmonary disease caused by M avium-intracellulare (MAC), M malmoense and M xenopi (REClari and RECipro). An optional comparison of immunotherapy with M vaccae vs no immunotherapy was also performed. METHODS: Progress was monitored annually during the 2 years of treatment and for 3 years thereafter. If the patient was not improving at 1 year the regimen was supplemented by the addition of the drug not received in the original allocation of treatment. RESULTS: 371 patients (186 REClari, 185 RECipro) entered the study (170 MAC, 167 M malmoense, 34 M xenopi). All-cause mortality was high for both groups (44% REClari, 43% RECipro); for MAC it was higher with REClari than with RECipro (48% vs 29%) but for M malmoense (42% vs 56%) and M xenopi (29% vs 47%) it was higher with RECipro (p = 0.006). 3% died from their mycobacterial disease (REClari = RECipro). At the end of treatment, 4% of REClari and 10% of RECipro patients still had positive cultures. Among those with negative cultures at the end of treatment, 6% of the REClari group and 4% of the RECipro group had relapsed. At 5 years 30% of the REClari group were known to have completed treatment as allocated and to be alive and cured compared with 21% of the RECipro group (p = 0.04), but this difference was principally due to those with M malmoense (REClari 38%, RECipro 20%). Patients with MAC or M xenopi were more likely to have a poor outcome than those with M malmoense (p = 0.004), with no difference between REClari and RECipro. Overall, 20% in each group were unable to tolerate the regimen allocated, Cipro being associated with more unwanted effects than Clari (16% vs 9%, p = 0.05). No significant differences in outcomes were found between M vaccae-treated patients and those not treated with M vaccae immunotherapy. CONCLUSION: Considering all three species together, there were no differences in outcome between the REClari and RECipro groups. Immunotherapy did not improve outcome. New therapies, optimised management of co-morbid conditions and a more holistic approach must be explored in the hope of improving outcome.

Tuberculosis control and the private health sector in Bolivia: a survey of pharmacies.

BACKGROUND: Bolivia is a high tuberculosis (TB) incidence country with a large private for-profit health sector. TB drug sales in private pharmacies are not illegal. OBJECTIVES: To measure the availability of TB drugs in private pharmacies, study vendors' attitudes, and explore the potential for collaboration between the public health sector and pharmacies. METHODS: Simulated clients visited a random sample of 100 pharmacies in the city of Cochabamba, presenting with a prescription for four TB drugs. After the survey, contacts were made with the local Pharmacist's Association. RESULTS: Twenty-five pharmacies sold at least one drug, 23 sold rifampicin and 16 sold isoniazid. Of 99 pharmacies unable to fill the whole prescription, 59 referred the client to another pharmacy, and 22 to the public services. Pharmacists said that rifampicin was often prescribed for non-TB indications, and that TB drug sales were of minimal contribution to their income. They agreed to stop selling the drugs and to refer clients seeking them to the public sector. CONCLUSION: This study has documented a small market for TB drugs sales in private pharmacies and provided the opportunity to start collaboration with the pharmacists. Our results suggest that the private sector contributes little to managing TB in Bolivia.

[Assessment of the use of a multicomponent drug in the treatment of new cases of pulmonary tuberculosis]. / Otsenka primeneniia mnogokomponentnogo preparata v lechenii vpervye vyiavlennykh bol'nykh tuberkulezom legkikh.

The multicomponent drug Mairin-P that contains isoniazid, 60 mg, rifampicin, 120 mg, pyrazinamide, 300 mg, and ethambutol hydrochloride, 225 mg, has been pharmacokinetically and clinically studied. There was no significant difference in the pharmacokinetic parameters of rifampicin as a component of Mairin-P and in combination with antitubercuous agents as free dosage forms. Treatment of first detected patients with pulmonary tuberculosis who isolate drug-sensitive Mycobacterium tuberculosis with Mairin-P is as effective as conventional treatment regimens with antituberculous drugs. Adverse reactions, including non-correctable one, due to the use of Mairin-P occur less frequently than to that of antituberculous drugs.