Months Of INH Research Articles

Safety and Tolerability of Six Months of Isoniazid Plus Pyridoxine or Three Months of Rifampicin for Tuberculosis among Subjects with Diabetes Mellitus: A Randomized Trial.

Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.

A pro-oxidant property of vitamin C to overcome the burden of latent Mycobacterium tuberculosis infection: A cross-talk review with Fenton reaction.

Tuberculosis (TB), caused by the bacillus M. tuberculosis, is one of the deadliest infectious illnesses of our day, along with HIV and malaria.Chemotherapy, the cornerstone of TB control efforts, is jeopardized by the advent of M. tuberculosis strains resistant to many, if not all, of the existing medications.Isoniazid (INH), rifampicin (RIF), pyrazinamide, and ethambutol are used to treat drug-susceptible TB for two months, followed by four months of INH and RIF, but chemotherapy with potentially harmful side effects is sometimes needed to treat multidrug-resistant (MDR) TB for up to two years. Chemotherapy might be greatly shortened by drugs that kill M. tuberculosis more quickly while simultaneously limiting the emergence of drug resistance.Regardless of their intended target, bactericidal medicines commonly kill pathogenic bacteria (gram-negative and gram-positive) by producing hydroxyl radicals via the Fenton reaction.Researchers have concentrated on vitamins with bactericidal properties to address the rising cases globally and have discovered that these vitamins are effective when given along with first-line drugs. The presence of elevated iron content, reactive oxygen species (ROS) generation, and DNA damage all contributed to VC's sterilizing action on M. tb in vitro. Moreover, it has a pleiotropic effect on a variety of biological processes such as detoxification, protein folding - chaperons, cell wall processes, information pathways, regulatory, virulence, metabolism etc.In this review report, the authors extensively discussed the effects of VC on M. tb., such as the generation of free radicals and bactericidal mechanisms with existing treatments, and their further drug development based on ROS production.

Factors associated with non-completion of TB preventive treatment in Brazil.

BACKGROUND: Among Brazilian initiatives to scale up TB preventive therapy (TPT) are the adoption of the 3HP regimen (12 weekly doses of rifapentine and isoniazid [INH]) in 2021 and the implementation in 2018 of the TPT surveillance information system. Since then, 63% of the 76,000 eligible individuals notified completed TPT. Recommended regimens in this period were 6H, 9H (6 or 9 months of INH) and 4R (4 months of rifampicin).OBJECTIVE: To analyse the factors associated with TPT non-completion.METHODS: We analysed the cohort of TPT notifications from 2018 to 2020. Robust variance Poisson regression model was used to verify the association of TPT non-completion with sociodemographic, clinical and epidemiological variables.RESULTS: Of the 39,973 TPT notified in the study period, 8,534 (21.5%) were non-completed, of which 7,858 (92.1%) were lost to follow-up. Age 15-60 years (relative risk [RR] 1.27, 95% confidence interval [95% CI] 1.20-1.35), TPT with isoniazid (RR 1.40, 95% CI 1.19-1.64) and Black/mixed race (RR 1.17, 95% CI 1.09-1.25) were associated with a higher risk of non-completion.CONCLUSION: Individuals in situations of social and financial vulnerability such as being Black/pardo race, younger and on longer TPT regimens were more likely to be associated with TPT incompletion.

The Drinkers\u2019 Intervention to Prevent Tuberculosis (DIPT) trial among heavy drinkers living with HIV in Uganda: study protocol of a 2\xd72 factorial trial

BackgroundThe risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda.MethodsThe Drinkers’ Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression.DiscussionThis study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence.Trial registrationClinicalTrials.gov NCT03492216. Registered on April 10, 2018

The IDEAL trial - a study protocol for a phase III randomized, double-blinded clinical trial assessing the ultra-short antibiotic prophylaxis of Isoniazid and Rifapentine in non-immunosuppressed patients with newly diagnosed latent tuberculosis

Introduction Tuberculosis (TB) is a global infectious disease that has plagued human beings for centuries. It currently ranks as one of the primary causes of death by a single agent. Treatment of latent TB (LTBI) is one of the cornerstones used to prevent the activation of TB. The current regimens are lengthy, associated with poor treatment adherence and several side effects. The need for shorter regimens is essential to control TB infection and accomplish the “End TB Strategy,” which has been proclaimed by the World Health Organization (WHO). Our study aims to provide a study design that assesses the efficacy of one month of Isoniazid (IHN) and Rifapentine (RFT) in non-immunosuppressed patients. Methods The proposed study will be a phase III, single-center, randomized, two-arms (1:1 ratio), double-blinded, placebo-controlled non-inferiority trial. We will include immunocompetent patients above the age of 18 with a new diagnosis of LTBI. Participants will be randomized, either receiving one month of INH with RFT or 6 months of INH alone with respective placebo to maintain blinding. The primary study outcome is the cumulative incidence of active TB in the studied treatment arms. The secondary outcome is the cumulative incidence and severity of adverse effects of the studied regimens. Discussion Given the scope and spread of LTBI around the globe, shorter and safer treatment options are of the utmost importance to eradicate TB. The proposed trial can contribute to this objective by improving the current standard of care. Potential disadvantages of the trial design include the need for many participants, trial duration, and costs.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

A shorter treatment regimen for latent tuberculosis infection holds promise for at-risk Canadians.

Despite recent success in reducing its incidence, tuberculosis remains a considerable challenge in Canada, particularly among foreign-born and Indigenous populations. A key component of the strategy for controlling the disease is the treatment of latent tuberculosis infection. The standard treatment consists of isoniazid (INH) daily for nine months. In recent years, shorter regimens have been developed in the hope of increasing rates of treatment acceptance and completion. Of these, the shortest and most recently developed is a combination of INH and rifapentine taken once weekly for 12 doses (3HP), typically using directly observed therapy (DOT). This regimen has been approved by the Food and Drug Administration in the United States but is not yet authorized in Canada. Based on a rapidly expanding number of observational studies and randomized controlled trials, 12 weeks of 3HP appears to have similar efficacy to nine months of INH, a favourable adverse event profile and potentially improved rates of treatment completion. Although rates of treatment acceptance, the role of self-administered therapy and the regimen's cost-effectiveness within the Canadian context remain uncertain, 3HP is a promising alternative to existing treatments for LTBI.

Recomendaciones en el tratamiento de la tuberculosis sensible (Según las Guías ATS/CDC/IDSA. 2016)

During 2016, American Thoracic Society: ATS, Centers for Disease Control and Prevention: CDC and Infectious Disease Society of America: IDSA jointly sponsored the development of Guidelines for the treatment of drug-susceptible tuberculosis using the P-I-C-O (Patient-Intervention-Comparison-Outcome) system to answer nine questions. The preferred regimen for treating adults with drug-susceptible tuberculosis, consider a 2 month intensive phase with isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) followed by a continuation phase of 4 months of INH and RIF For patients who have cavitation on the initial chest radiograph and have positive cultures at completion of 2 months therapy, it is recommended to extend the continuation phase to prevent relapse. EMB can be discontinued as soon as susceptibility to INH and RIF is demonstrated. The guidelines also makes recommendations for the management in different clinical situations as in patients co-infected with HIV and in extrapulmonary tuberculosis. In tuberculous pericarditis no longer is recommended the routinely use of corticosteroids together with the anti TB treatment. In the case of tuberculous meningitis it is recommended the addition of corticosteroids and to extend the continuation phase to 9-12 months.

Fighting tuberculosis by drugs targeting nonreplicating Mycobacterium tuberculosis bacilli.

Current tuberculosis (TB) treatment requires 6 months of combination therapy with isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol for active TB and 9 months of INH or 3 months of rifapentine (RFP) + INH for latent TB. The lungs of patients with active and latent TB contain heterogeneous mixtures of cellular and caseous granulomas harboring Mycobacterium tuberculosis bacilli ranging from actively replicating (AR) to nonreplicating (NR), phenotypically drug-resistant stages. Several in vitro models to obtain NR cells were reported, including exposure to hypoxia, nutrient starvation, acid + nitric oxide, and stationary phase. Overall, these models showed that RIF, RFP, PA-824 (PA), metronidazole (MZ), bedaquiline (BQ), and fluoroquinolones were the most active drugs against NR M. tuberculosis. In hypoxia at pH 5.8, some combinations killed AR plus NR cells, as shown by lack of regrowth in liquid media, whereas in hypoxia at pH 7.3 (the pH of the caseum), only RIF and RFP efficiently killed NR bacilli while several other drugs showed little effect. In conventional mouse models, combinations containing RFP, BQ, PA, PZA, moxifloxacin, sutezolid, linezolid, and clofazimine sterilized animals in ≤2 months, as shown by lack of viable bacilli in lung homogenates after 3 months without therapy. Drugs were less effective in C3HeB/FeJ mice forming caseous granulomas. Overall, in vitro observations and in vivo studies suggest that the search for new TB drugs could be addressed to low lipophilic molecules (e.g., new rpoB inhibitors with clogP < 3) killing NR M. tuberculosis in hypoxia at neutral pH and reaching high rates of unbound drug in the caseum.

Baseline abnormal liver function tests are more important than age in the development of isoniazid-induced hepatoxicity for patients receiving preventive therapy for latent tuberculosis infection.

One of the cornerstones of Australia's public health programmes to eliminate tuberculosis (TB) is the identification and treatment of latent tuberculosis infection (LTBI). The main aim of this study is to determine the demographics, compliance, completion rates and adverse events of patients on preventive therapy (PT) for LTBI at our institution. The secondary aim is to determine the rates of isoniazid (INH) hepatotoxicity and identify any contributory factors. The method used was an audit using medical records of 100 consecutive patients (2010-2014) treated with PT for LTBI. Seventy-two patients with confirmed LTBI started 9 months of INH and 22 started 4 months of rifampicin (RIF). The median age was 30 years. Half the patients were born in high TB-prevalence countries. Fifty-six per cent were contacts of index cases with confirmed TB, and 26% were pre-immunosuppression. Seventy-seven per cent completed PT with adequate compliance. Thirty-three per cent on INH and 23% on RIF experienced some liver function test (LFT) abnormality while on treatment. INH was ceased in 3% due to asymptomatic hepatic dysfunction (transaminases >5x upper limit of normal). No patients had permanent liver damage. Significant risk factors for liver dysfunction during PT were risk factors for liver disease (χ(3)(2) = 8.7; P = 0.03) or abnormal pre-therapy LFT (χ(3)(2)= 22.4; P < 0.001). No patients developed active TB. The completion rate of 77% and rate of INH-induced hepatic dysfunction of 3% is comparable with the literature. We found no age association with the risk of INH-induced hepatic dysfunction; however, there was a significant and linear association with the degree of liver function abnormality during INH therapy and the presence of abnormal baseline LFT. Routine LFT monitoring allowed early cessation of INH in those with significant but asymptomatic hepatitis who did not meet criteria for ATS/CDC LFT monitoring.

The Influence of Pyrazinamide Monoresistance on Treatment Outcomes in Tuberculosis Patients from Southern China

This study aimed to explore the influence of pyrazinamide (PZA) monoresistance on the treatment outcome of otherwise drug susceptible tuberculosis (TB). A cohort of 194 TB patients that were infected with strains susceptible to isoniazid (INH), rifampin (RIF) and ethambutol (EMB) were included in a retrospective study at the Guangzhou Chest Hospital. We reported 148 (76.3%) PZA- susceptible TB cases and 46 (23.7%) PZA-monoresistance TB cases identified by the BACTEC MGIT 960 system. All patients were treated with the standard 6 months WHO recommended regimen, which included 2 months of INH + RIF + EMB + PZA in the intensive-phase, and the subsequent 4 months of INH + RIF during continuation-phase. Bacterial burden in the lungs was estimated using sputum smear acid-fast bacillary count while the lung lesions and cavitations were examined by X-ray at the end of first 2 months of chemotherapy. After intensive-phase treatment, there were 164 (84.5%) cases of smear-negative conversion and 151 (77.9%) cases of total or partial lesion elimination. The rates of smear-negative conversion (78.3%) and lesion elimination (39.1%) of the PZA-monoresistant patients were similar with the PZA-sensitive group (P > 0.05). However, lung cavitation was more likely to be resolved in PZA-sensitive patients than in the PZA-patients (X2 = 9.623, P = 0.002). The smear-negative conversion rates were 95.9% for the PZA-sensitive patients and 87.0% for the PZA-monoresistant patients after 6 months of treatment (X2 = 3.461, P = 0.063). Together, our data suggest that PZA-monoresistance contributes to the delay of resolution of the lung cavitations in the Southern China population without affecting the sputum conversion and lesion elimination rates.

939Electronic Mail (email) Reminders as an Alternative to Directly Observed Therapy (DOT) for the Treatment of Latent Tuberculosis Infection (LTBI) using 12 weeks of Rifapentine and INH (R plus I) for Healthcare Workers (HCWs)

Figure 2. Background: HCWs with LTBI are encouraged to be treated. Obstacles to the initiation and completion of treatment include concerns about the duration (especially 9 months of INH) and about side effects. With the aim of reducing the impact of these issues, MSK introduced the newly endorsed 12-week regimen of once weekly R plus I in January 2013 for HCWs. Additionally, email reminders, urine color checks, and feedback about compliance from MSK’s pharmacy were utilized in lieu of DOT.

Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

RationaleGlobal tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown. ObjectivesEvaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI). MethodsEighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥15mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination. ResultsBaseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20±4mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment. ConclusionBCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).

Successful management of latent tuberculosis infection in an underserved community by a student-run free clinic.

The management of latent tuberculosis infection (LTBI) most commonly consists of a nine-month course of isoniazid (INH) therapy and is complicated by low adherence and completion rates. The Latent Tuberculosis Initiative at the HAVEN Free Clinic was developed to provide LTBI treatment to an underserved, high-risk, foreign-born population. We conducted a retrospective chart review to evaluate the program. Of 39 patients enrolled, 26 (67%) successfully completed nine months of INH, eight (21%) discontinued, and five (12%) were lost to follow-up. Patients had a median of nine encounters during the course of treatment and mean self-reported medication adherence was 29/30 pills/month (96%). Median days-of-treatment was 273, 95, and 63 among completion, discontinuation, and lost to follow-up groups, respectively (p &lt; .0001). There was one death in the program, related to a complication of a diagnostic procedure in a patient who had developed INH toxicity. These results are comparable to the most successful published programs (50-65% six-month completion rates), suggesting that student-run clinics serving high-risk populations may contribute to LTBI management and TB control efforts.

Prophylaxis for Latent Tuberculosis Infection Prior to Anti–Tumor Necrosis Factor Therapy in Low‐Risk Elderly Patients With Rheumatoid Arthritis: A Decision Analysis

To determine if low-risk elderly patients with rheumatoid arthritis (RA) who screen positive for latent tuberculosis (TB) infection prior to anti–tumor necrosis factor (anti-TNF) therapy should be given isoniazid (INH). A Markov model was developed. The base case was a patient age 65 years with RA starting anti-TNF therapy with a positive tuberculin skin test (TST) finding of 5–9 mm, who was born in a country with low TB prevalence and had no other TB risk factors. The decision was 9 months of INH or not. The primary outcome was quality-adjusted life expectancy. Multiple sensitivity analyses were performed. No prophylaxis was favored, with a gain of 1.1 quality-adjusted life days, but the decision was sensitive to several variables. Prophylaxis was favored for patients ages <61 years, if the relative risk (RR) of TB reactivation with RA alone was >2.5, if the RR with anti-TNF therapy was >5.8, or if the utility associated with INH therapy was >0.98. Prophylaxis was also preferred for patients with a TST result >10 mm and for patients from higher risk countries. If 6 months of INH or 4 months of rifampin were used, prophylaxis was preferred, providing that therapy reduced the risk of TB reactivation by >47% and >27%, respectively. Withholding prophylaxis prior to anti-TNF therapy may be reasonable for low-risk elderly RA patients with a TST finding of 5–9 mm, although the decision is sensitive to patient preferences. For patients age <61 years from a higher risk country, or with a TST finding >10 mm, prophylaxis is preferred.

Ethambutol and pyrazinamide-induced toxic epidermal necrolysis in an immunocompetent adult with tuberculosis

Ethambutol and pyrazinamide-induced toxic epidermal necrolysis in an immunocompetent adult with tuberculosis

Feasibility and Efficacy of Isoniazid Prophylaxis for Latent Tuberculosis in HIV-Infected Clients Patients in Thailand

A prospective study was conducted in 4339 HIV-positive clients at the Thai Red Cross AIDS Research Centre (TRC-ARC) Anonymous clinic, Bangkok, Thailand between January 2003 and April 2008. A tuberculin skin test (TST) was done for all patients without a previous history of tuberculosis (TB). Nine months of isoniazid (INH) was given for all positive TST/no active TB. TST-negative clients were asked to repeat the TST annually. The study aim was to evaluate the feasibility and efficacy of INH prophylaxis for preventing TB in HIV-positive Thai patients. Of those patients, 4111 (94.7%) had a TST done; 1157 (28.1%) were TST positive and 799 patients started INH prophylaxis. In all, 551 (69%) and 633 (79.2%) patients completed 9 months and 6 months of INH, respectively; 176 (20.2%) patients had a negative TST at baseline and subsequently converted to positive. Only patients with a baseline CD4 >200 cells/μL (p=0.000) and currently on antiretroviral (ARV) treatment (p=0.000) were related to having a positive TST. This baseline CD4 level was also significantly related to higher INH completion rates at 6 months (p=0.000). Interestingly, none of INH completion patients developed active TB. The feasibility of INH prophylaxis in TST-positive patients in this setting is possible. However, the long-term advantage of INH prophylaxis in terms of TB prevention, especially in HIV-1-infected patients on highly active antiretroviral therapy (HAART), is still an issue that needs more research.

Treatment of latent tuberculosis infection: An update

Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self-administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy-in experimental studies in mice and randomized trials, largely in HIV-infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV-infected persons and children, in non-HIV-infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH-possibly because two drugs are taken rather than one. The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono-rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.

The Vietnamese Khin Population Harbors Particular N-Acetyltransferase 2 Allele Frequencies

Vietnam ranks 13th among the 23 countries that must deal with 80% of global deaths from tuberculosis (1). The National Tuberculosis Control Program of Vietnam implemented the WHO DOTS (directly observed therapy, short course) strategy in 1989. The standard treatment regimen for previously untreated patients consists of 2 months of streptomycin, isoniazid (INH), rifampin, and pyrazinamide, followed by 6 months of INH and ethambutol (the 2SHRZ/6HE regimen). INH, a central component of this chemotherapy, is extensively metabolized by the polymorphic N -acetyltransferase 2 (NAT2) enzyme. N -acetyltransferase 2 (arylamine N -acetyltransferase) ( NAT2 ) gene polymorphisms are associated with individual phenotypes generally classified as INH rapid (homozygous or heterozygous) and slow acetylators. Among the described NAT2 alleles, NAT2*5 , * 6 , * 7 , 12 *, * 14 , * 17 , and * 19 have been associated with the slow acetylator phenotype, and NAT2*4 and * 13 are associated with fast acetylation. Under treatment with standard dosages, patients who are slow metabolizers …

Safety of Treatment of Latent Tuberculosis Infection in Compensated Cirrhotic Patients During Transplant Candidacy Period

Treatment of latent tuberculosis infection with isoniazid (INH) or rifampin (RIF) is controversial in liver transplant candidates due to potential hepatotoxicity. In this study, treatment of latent tuberculosis during transplant candidacy period is explored, and relevant literature is reviewed. Liver transplant candidates with latent tuberculosis infection by positive tuberculin skin test (>5 mm) were prospectively enrolled and treated with 9 months of INH or 4 months of RIF, and were monitored monthly for their liver enzyme profiles, adverse effects, compliance, and completion rate. Four of nine patients with INH had asymptomatic, mild elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) versus none of five patients in the RIF group. Two cases of elevations were attributed to INH. Two other cases were attributed to alcoholism or active chronic hepatitis B virus infection. Only one patient in the INH group experienced symptoms possibly attributed to INH hepatotoxicity. Compliance was 100% per patient reporting. Completion rates were 79% for INH and 100% for RIF. No fulminant hepatic failure or death was observed. Treatment of latent tuberculosis in liver transplant patients during their candidacy with INH or RIF appears to be a safe, viable option, if carefully monitored for adverse effects and liver enzymes.