rifampin and Latent-Tuberculosis

Abdominal pain represents a frequent symptom for referral to emergency departments and/or internal medicine outpatient setting. Similarly, fever, fatigue and weight loss are non-specific manifestations of disease. The present case describes the diagnostic process in a patient with abdominal pain and a palpable abdominal mass. Abdominal ultrasonography confirmed the presence of a mass in the mesogastrium. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans oriented toward calcific lymphadenopathies with increased metabolism in the positron emission tomography-computed tomography (PET-CT) scan. Laboratory examinations were inconclusive, although serology for Brucella and the Quantiferon test were positive. After multidisciplinary discussion, the patient underwent surgical excision of the abdominal mass. Histological examination excluded malignancies and oriented toward brucellosis in a patient with latent tuberculosis. The patient was treated with rifampin 600 mg qd and doxycycline 100 mg bid for 6 weeks with resolution of the symptoms. In addition, rifampin was continued for a total of 6 months in order to treat latent tuberculosis. This case underlines the need for a multidisciplinary approach in the diagnostic approach to abdominal lymphadenopathies.

Topics: Abdominal Pain; Brucellosis; Humans; Latent Tuberculosis; Lymphadenopathy; Lymphoma; Positron Emission Tomography Computed Tomography; Rifampin; Tuberculosis

3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R.. We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs.. We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found.. In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment.. None.. For the French and Spanish translations of the abstract see Supplementary Materials section.

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Network Meta-Analysis; Rifampin; Tuberculosis

Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality.. To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF).. PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023.. English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded.. Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available.. Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms.. A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339).. No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

Topics: Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Latent Tuberculosis; Mass Screening; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Rifampin; United States

Tuberculosis (TB), caused by the bacillus

Topics: Antitubercular Agents; Ascorbic Acid; Humans; Latent Tuberculosis; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Reactive Oxygen Species; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant; Vitamins

The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings, with advanced sensitivity and specificity. Early detection of TB can be challenging, but Xpert has improved the efficacy of the diagnostic process. Nevertheless, the accuracy of Xpert varies according to different diagnostic specimens and TB infection sites. Therefore, the selection of adequate specimens is critical when using Xpert to identify suspected TB. As such, we have conducted a meta-analysis to evaluate the effectiveness of Xpert for diagnosis of different TB types using several specimens.. We conducted a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization clinical trials registry center, covering studies published from Jan 2008 to July 2022. Data were extracted using an adapted version of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies. Where appropriate, meta-analysis was performed using random-effects models. The risk of bias and level of evidence was assessed using the Quality in Prognosis Studies tool and a modified version of the Grading of Recommendations Assessment, Development, and Evaluation. RStudio was utilized to analyze the results, employing the. After excluding duplicates, a total of 2163 studies were identified, and ultimately, 144 studies from 107 articles were included in the meta-analysis based on predetermined inclusion and exclusion criteria. Sensitivity, specificity and diagnostic accuracy were estimated for various specimens and TB types. In the case of pulmonary TB, Xpert using sputum (0.95 95%CI 0.91-0.98) and gastric juice (0.94 95%CI 0.84-0.99) demonstrated similarly high sensitivity, surpassing other specimen types. Additionally, Xpert exhibited high specificity for detecting TB across all specimen types. For bone and joint TB, Xpert, based on both biopsy and joint fluid specimens, demonstrated high accuracy in TB detection. Furthermore, Xpert effectively detected unclassified extrapulmonary TB and tuberculosis lymphadenitis. However, the Xpert accuracy was not satisfactory to distinguish TB meningitis, tuberculous pleuritis and unclassified TB.. Xpert has exhibited satisfactory diagnostic accuracy for most TB infections, but the efficacy of detection may vary depending on the specimens analyzed. Therefore, selecting appropriate specimens for Xpert analysis is essential, as using inadequate specimens can reduce the ability to distinguish TB.. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370111, identifier CRD42022370111.

Topics: Antibiotics, Antitubercular; Humans; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

We conducted an updated network meta-analysis to elucidate the best regimen for latent tuberculosis infection (LTBI).. We searched the PubMed, Embase, and Cochrane Library databases on 16 August 2021 to perform an updated network meta-analysis. Only randomised controlled trials on populations with LTBI that reported the efficacy for preventing incident tuberculosis or the completion rates of treatment regimens were included. The Cochrane Collaboration tool was used to assess the risk of bias. We tested for possible global inconsistency with a χ. We identified 27 studies that matched our inclusion criteria; the risk of bias was mostly low. Rifampicin for four months (RFMP-4) was the most likely to be effective (probability: 56.3%) and the second most likely treatment to be completed (probability: 22.4%). By applying a multidimensional scaling approach for ranking based on a scatterplot with the surface under the cumulative ranking values for efficacy and completion rates, RFMP-4 was deemed the best choice for treating LTBI. Similar results were demonstrated after sensitivity analysis.. This updated network meta-analysis revealed RFMP-4 to be the best choice for treating LTBI, per simultaneous consideration of efficacy and completion rates.

Topics: Humans; Latent Tuberculosis; Network Meta-Analysis; Rifampin

We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents.. A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty.. Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15-25 mg/kg/week) plus rifapentine (300-900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated to more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4-6 mg/kg/day vs. 10 mg/kg/3x per week).. Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.

Topics: Adolescent; Antitubercular Agents; Bayes Theorem; Child; Humans; Isoniazid; Latent Tuberculosis; Network Meta-Analysis; Rifampin

The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens.. We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis.. A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001).. The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.

Topics: Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Latent Tuberculosis; Medication Adherence; Middle Aged; Rifampin; Young Adult

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations-isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for

Topics: Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen's superior safety and adherence.. We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving the 3HP regimen via DOT between 2017 and 2019. Frequencies of selected outcomes were compared to previously published data collected in a literature review.. In this retrospective chart review, pediatric patients ages 2-20 years receiving 3HP with DOT for latent tuberculosis experienced frequent adverse events, more severe adverse events such as anaphylaxis, and higher treatment discontinuation than that which has been previously reported in the literature. Of note, our cohort's race/ethnicity differed from the cohorts described in the literature.. Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the 3HP regimen's safety and tolerability.

Topics: Adolescent; Adult; Antitubercular Agents; Child; Child, Preschool; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Retrospective Studies; Rifampin; Young Adult

Topics: Adolescent; Adult; Antitubercular Agents; Child; Developing Countries; Drug Therapy, Combination; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Young Adult

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Dose-Response Relationship, Drug; Female; Humans; Latent Tuberculosis; Male; Middle Aged; Rifampin; Young Adult

Tuberculosis (TB) remains a common cause of death globally. A regimen of 12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT-3) has recently been recommended by the World Health Organization for the treatment of latent TB infection (LTBI). We aimed to determine whether the INH/RPT-3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months.. We searched MEDLINE, Embase, CENTRAL, PubMed, ICTRP, clinicaltrials.gov, and Canadian Agency for Drugs and Technologies in Health's Gray Matters Light for randomized, postmarketing, and comparative nonrandomized studies of patients with confirmed LTBI that reported the frequency of at least 1 adverse event of relevance for a regimen of interest. The search included studies published until March 2017. The frequencies of adverse events were extracted and are presented descriptively.. Data from 23 randomized and 55 nonrandomized studies were included. Although inconsistent event reporting and high heterogeneity limited comparisons, the adverse event profile of INH/RPT-3 appeared generally favorable. Flu-like reactions were reported with an increased frequency and hepatotoxicity with a lower frequency than standard treatment.. While INH/RPT-3 had an overall low frequency of adverse events compared to INH monotherapy, reporting of adverse events for many regimens was limited meaning results should be interpreted cautiously. Future studies of LTBI treatment would benefit from more complete collection and reporting of adverse events and more consistent definitions of hepatotoxicity.

Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Incidence; Isoniazid; Latent Tuberculosis; Respiratory Tract Diseases; Rifampin

Topics: Adolescent; Antitubercular Agents; Child; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Latent tuberculosis infection diagnosis and treatment is a strategic priority for eliminating tuberculosis in the U.S. The Centers for Disease Control and Prevention has recommended the short-course regimen of 3-month isoniazid-rifapentine administered by directly observed therapy. However, longer-duration regimens remain the most widely prescribed latent tuberculosis infection treatments. Limitation on adoption of 3-month isoniazid-rifapentine in the U.S. might be because of patients' preference for self-administered therapy, providers' lack of familiarity with 3-month isoniazid-rifapentine, or lack of resources to support directly observed therapy. This review examines the most recent evidence regarding 3-month isoniazid-rifapentine's effectiveness, safety, and treatment completion when directly compared with other latent tuberculosis infection regimens primarily comprising 9-month isoniazid treatment.. Using Community Guide methodology, reviewers identified, evaluated, and summarized available evidence published during January 2006-June 2017. Analysis of the data was completed in 2017.. The analysis included 15 unique studies. Three-month isoniazid-rifapentine was determined to be equal to other latent tuberculosis infection regimens in effectiveness (OR=0.89, 95% CI=0.46, 1.70), and has higher treatment completion (87.5%, 95% CI=83.2%, 91.3%) compared with other latent tuberculosis infection regimens (65.9%, 95% CI=53.5%, 77.3%). Three-month isoniazid-rifapentine was associated with similar risk to other latent tuberculosis infection regimens for adverse events (relative risk=0.59, 95% CI=0.23, 1.52); discontinuing treatment because of adverse events (relative risk=0.48, 95% CI=0.17, 1.34); and death (relative risk=0.79, 95% CI=0.56, 1.11).. The 3-month isoniazid-rifapentine regimen is as safe and effective as other recommended latent tuberculosis infection regimens and achieves significantly higher treatment completion rates.

Topics: Directly Observed Therapy; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Time Factors; United States

First-line therapy for active tuberculosis (TB) has remained unchanged for nearly 40 years. Isoniazid, rifampin, pyrazinamide, and ethambutol for the initial two-month phase followed by isoniazid and rifampin for 4 to 7 months is standard treatment for people at low risk for drug-resistant disease. Directly-observed therapy (DOT) remains the standard of care for pulmonary TB. Virtual treatment monitoring using digital technologies is becoming more common as a way to provide a more patient-centered approach to care. Attempts to shorten treatment duration have been unsuccessful based on recent clinical trials evaluating the role of fluoroquinolones. Treatment-shortening trials using higher doses of rifamycins are currently underway. Recently approved medications for TB treatment are recommended only for drug-resistant disease, but novel agents in varying stages of development are being evaluated. Rifamycin-based regimens for latent TB infection (LTBI) have been successful in preventing progression to TB disease. Once-weekly isoniazid and rifapentine for 12 weeks by DOT was shown to be safe and effective compared with 9 months of isoniazid. The same regimen was shown to have acceptable treatment completion when given self-administered. Newer studies are investigating even shorter LTBI treatment with durations of less than 2 months. Treatment of LTBI in people likely infected with multidrug resistant TB is very limited, but one observational study found that fluoroquinolones appear to be effective. The first randomized trials for treating LTBI in contacts to MDR-TB are currently enrolling.

Topics: Antitubercular Agents; Directly Observed Therapy; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Randomized Controlled Trials as Topic; Rifampin

Uptake of preventive treatment for tuberculosis (TB) remains poor. A 3-month regimen of rifapentine (RPT) plus isoniazid (INH) (3HP) could facilitate its scale-up. We conducted a systematic review to assess the effects of 3HP compared with daily 6- or 9-month INH monotherapy.. We searched the following databases to identify randomised controlled trials: PubMed, Embase, the Web of Science, Cochrane Central Register of Controlled Trials, three ongoing trial registers and conference abstracts up to 24 January 2017. Where possible, we pooled data using a random-effects model.. Four studies were included. Of those, we included two studies that compared 3HP with daily 6- or 9-month INH (6/9H) among adults with human immunodeficiency virus (HIV) co-infection, one among HIV-negative adults and one among predominantly HIV-negative children and adolescents. Risk of active TB was not significantly different between 3HP and 6/9H (risk ratio [RR] 0.73, 95%CI 0.23-2.29, in adults with HIV; RR 0.44, 95%CI 0.18-1.07, in adults without HIV; RR 0.13, 95%CI 0.01-2.54, in children and adolescents). Risk of hepatotoxicity was significantly lower in the 3HP group among adults with HIV (RR 0.26, 95%CI 0.12-0.55) and those without HIV (RR 0.16, 95%CI 0.10-0.27). 3HP was also associated with a higher completion rate in all subgroups.. HP was shown to have a preventive effect similar to that of INH monotherapy, with fewer adverse events and higher completion rates. 3HP can contribute significantly to the scale-up of preventive treatment.

Topics: Adolescent; Adult; Antibiotics, Antitubercular; Child; Directly Observed Therapy; Drug Administration Schedule; Drug Therapy, Combination; HIV Seronegativity; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Tuberculosis, Pulmonary

We conducted a systematic review and network meta-analysis (NMA) to examine the efficacy and completion rates of treatments for latent tuberculosis infection (LTBI). While a previous review found newer, short-duration regimens to be effective, several included studies did not confirm LTBI, and analyses did not account for variable follow-up or assess completion.. We searched MEDLINE, Embase, CENTRAL, PubMed, and additional sources to identify RCTs in patients with confirmed LTBI that involved a regimen of interest and reported on efficacy or completion. Regimens of interest included isoniazid (INH) with rifapentine once weekly for 12 weeks (INH/RPT-3), 6 and 9 months of daily INH (INH-6; INH-9), 3-4 months daily INH plus rifampicin (INH/RFMP 3-4), and 4 months daily rifampicin alone (RFMP-4). NMAs were performed to compare regimens for both endpoints.. Sixteen RCTs (n = 44,149) and 14 RCTs (n = 44,128) were included in analyses of efficacy and completion. Studies were published between 1968 and 2015, and there was diversity in patient age and comorbidities. All regimens of interest except INH-9 showed significant benefits in preventing active TB compared to placebo. Comparisons between active regimens did not reveal significant differences. While definitions of regimen completion varied across studies, regimens of 3-4 months were associated with a greater likelihood of adequate completion.. Most of the active regimens showed an ability to reduce the risk of active TB relative to no treatment, however important differences between active regimens were not found. Shorter rifamycin-based regimens may offer comparable benefits to longer INH regimens. Regimens of 3-4 months duration are more likely to be completed than longer regimens.

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Male; Network Meta-Analysis; Rifampin; Time Factors

There are approximately 56 million people who harbor Mycobacterium tuberculosis that may progress to active tuberculosis (TB) at some point in their lives. Modeling studies suggest that if only 8% of these individuals with latent TB infection (LTBI) were treated annually, overall global incidence would be 14-fold lower by 2050 compared to incidence in 2013, even in the absence of additional TB control measures. This highlights the importance of identifying and treating latently infected individuals, and that this intervention must be scaled up to achieve the goals of the Global End TB Strategy. The efficacy of LTBI treatment is well established, and the most commonly used regimen is 9 months of daily self-administered isoniazid. However, its use has been hindered by limited provider awareness of the benefits, concern about potential side effects such as hepatotoxicity, and low rates of treatment completion. There is increasing evidence that shorter rifamycin-based regimens are as effective, better tolerated, and more likely to be completed compared to isoniazid. Such regimens include four months of daily self-administered rifampin monotherapy, three months of once weekly directly observed isoniazid-rifapentine, and three months of daily self-administered isoniazid-rifampin. The success of LTBI treatment to prevent additional TB disease relies upon choosing an appropriate regimen individualized to the patient, monitoring for potential adverse clinical events, and utilizing strategies to promote adherence. Safer, more cost-effective, and more easily completed regimens are needed and should be combined with interventions to better identify, engage, and retain high-risk individuals across the cascade from diagnosis through treatment completion of LTBI.

Topics: Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Medication Adherence; Mycobacterium tuberculosis; Rifampin; Treatment Outcome

Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI.. To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children.. PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied.. Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB).. 2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol.. The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy.. Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies.. Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin.. U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).

Topics: Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Child; Drug Combinations; Humans; Isoniazid; Latent Tuberculosis; Network Meta-Analysis; Pyrazinamide; Rifampin

One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them. Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.

Topics: Animals; Antibiotics, Antitubercular; Dose-Response Relationship, Drug; Half-Life; Humans; Latent Tuberculosis; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Tuberculosis

Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain.. To estimate health outcomes, costs, and cost-effectiveness of LTBI testing and treatment among non-US born residents with and without medical comorbidities.. Decision analytic tree and Markov cohort simulation model among non-US born residents with no comorbidities, with diabetes, with HIV infection, or with end-stage renal disease (ESRD) using a health care sector perspective with 3% annual discounting. Strategies compared included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). All strategies were coupled to treatment with 3 months of self-administered rifapentine and isoniazid.. Number needed to test and treat to prevent 1 case of TB reactivation, discounted quality-adjusted life-years (QALYs), discounted lifetime medical costs, and incremental cost-effectiveness ratios (ICERs).. Improving health outcomes increased costs, with choice of test dependent on willingness to pay. Strategies ranked by ascending costs and benefits: no testing, confirm positive, TST, IGRA, and confirm negative. The ICERs varied by non-US born patient risk group: patients with no comorbidities, IGRA was likely cost-effective at $83 000/QALY; patients with diabetes, both confirm positive ($53 000/QALY) and IGRA ($120 000/QALY) were likely cost-effective; patients with HIV, confirm negative was clearly preferred ($63 000/QALY); and patients with ESRD, no testing was cost-effective. Increased LTBI prevalence and reduced return for TST reading improved IGRA's relative performance. In 10 000 probabilistic simulations among non-US born patients with no comorbidities, with diabetes, and with HIV, some form of testing was virtually always cost-effective. These simulations highlight the uncertainty of test choice for non-US born patients with no comorbidities and non-US born patients with diabetes, but strategies including IGRA were preferred in over 60% of simulations for all non-US born populations except those with ESRD.. Testing for and treating LTBI among non-US born residents with and without selected comorbidities is likely cost-effective except among those with ESRD in whom competing risks of death limit benefits. Strategies including IGRA fell below a $100 000/QALY willingness-to-pay threshold for non-US born patients with no comorbidities, patients with diabetes, and patients with HIV.

Topics: Antitubercular Agents; Bayes Theorem; Comorbidity; Cost-Benefit Analysis; Decision Trees; Emigrants and Immigrants; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Markov Chains; Quality-Adjusted Life Years; Rifampin; Tuberculin Test; United States

Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug-drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored.

Topics: Antibiotics, Antitubercular; Diabetes Mellitus; Drug Interactions; Humans; Hypoglycemic Agents; Latent Tuberculosis; Rifampin; Tuberculosis

The management of latent tuberculosis (LTBI) in children represents an important issue for paediatricians because of the disease burden, the lack of a gold standard for the diagnosis and the high annual risk of progression to active disease. Areas covered: A review of English language articles on LTBI in children, published between the 1st of January 2010 and the 1st of July 2016, was conducted using multiple keywords and standardized terminology in PubMed database. This review provides an updated overview of the available tests for LTBI diagnosis in children, management strategies and treatment options. Expert commentary: Two tests are available for LTBI diagnosis: tuberculin skin test and interferon-gamma release assays, both with a suboptimal specificity and sensitivity, and both with the lack of capability in distinguishing between infection and disease. Several new markers have been identified but further studies are needed. Among all treatment regimes, because of the high safety and efficacy profile showed and to avoid the poor completion rate, the treatment with a three-month course of isoniazid and rifampicin is currently recommended. New vaccines are needed because of the spread of the disease despite BCG vaccination in high risk countries. Currently, 15 new vaccines are in the pipeline.

Topics: Antitubercular Agents; Biomarkers; Chemokine CXCL10; Child; Disease Management; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunospot Assay; Humans; Interferon-gamma; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; Tuberculin Test; Tuberculosis Vaccines; Tuberculosis, Pulmonary

The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV-infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present.

Topics: Antitubercular Agents; Disease Management; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin; Risk Factors; Transplant Recipients; World Health Organization

Treatment for latent tuberculous infection (LTBI) reduces the risk of tuberculosis (TB) disease. Shorter, rifamycin-containing regimens have been shown to be as effective as 6 months of isoniazid and superior with regard to safety and completion rate. It is unknown whether preventive therapy with rifamycins increases resistance to the drugs used.. To determine whether treatment for LTBI with rifamycin-containing regimens leads to significant development of resistance against rifamycins.. Systematic review and meta-analysis.. We included six randomised-controlled trials of rifamycin-containing regimens for LTBI treatment that reported drug resistance. There was no statistically significant increased risk of rifamycin resistance after LTBI treatment with rifamycin-containing regimens compared to non-rifamycin-containing regimens (RR 3.45, 95%CI 0.72-16.56; P = 0.12) or placebo (RR 0.20, 95%CI 0.02-1.66; P = 0.13).. Preventive treatment with rifamycin-containing regimens does not significantly increase rifamycin resistance. Programmatic management of LTBI requires the creation of sound surveillance systems to monitor drug resistance.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Child; Drug Resistance, Bacterial; Female; Humans; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Odds Ratio; Randomized Controlled Trials as Topic; Rifampin; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Young Adult

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Practice Guidelines as Topic; Rifampin; Risk Factors

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

Topics: Antirheumatic Agents; Antitubercular Agents; Coinfection; Comorbidity; Disease Management; Drug Users; Emigrants and Immigrants; Evidence-Based Medicine; Health Personnel; HIV Infections; Humans; Ill-Housed Persons; Interferon-gamma Release Tests; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Mass Screening; Practice Guidelines as Topic; Prisoners; Public Health; Radiography, Thoracic; Renal Dialysis; Rifampin; Risk Assessment; Silicosis; Substance-Related Disorders; Transplant Recipients; Tuberculin Test; Tumor Necrosis Factor-alpha; World Health Organization

Prophylactic treatment of latent tuberculosis infection (LTBI) is necessary for controlling TB in low-incidence settings. However, treatment is often limited by poor completion rates.. At a community health center serving low-income Hispanics, treatment completion among patients accepting 12 weekly doses of isoniazid (INH) plus rifapentine (RPT) administered as directly observed therapy (DOT) was compared with that among patients accepting nine months of daily self-administered INH during 2012 and 2013 (n=139).. Among patients who agreed to treatment, INH-RPT combination therapy was associated with higher completion rates (OR 3.06; 95% CI, 1.23-7.62; p=.016) when compared to INH only. Overall completion rates were 77.8% (35/45) for INH-RPT combination therapy and 52.1% (49/94) for INH monotherapy.. High completion rates for LTBI treatment can be achieved at a community health center using INH-RPT administered via DOT. Greater success treating with INH-RPT may be attributed to DOT strategy and a shorter treatment regimen.

Topics: Community Health Centers; Directly Observed Therapy; Drug Therapy, Combination; Hispanic or Latino; Humans; Isoniazid; Latent Tuberculosis; Medication Adherence; Poverty; Rifampin; Wisconsin

The treatment of latent tuberculosis infection (LTBI) has been established as valid for patients at high risk for developing active tuberculosis. Treatment of LTBI is also considered an important strategy for eliminating tuberculosis (TB) in Japan. In recent years, interferon-gamma release assays have come into widespread use; isoniazid (INH) preventive therapy for HIV patients has come to be recommended worldwide; and there have been increases in both types of biologics used in the treatment of immune diseases as well as the diseases susceptible to treatment. In light of the above facts, the Prevention Committee and the Treatment Committee of the Japanese Society for Tuberculosis have jointly drafted these guidelines. In determining subjects for LTBI treatment, the following must be considered: 1) risk of TB infection/ development; 2) infection diagnosis; 3) chest image diagnosis; 4) the impact of TB development; 5) the possible manifestation of side effects; and 6) the prospects of treatment completion. LTBI treatment is actively considered when relative risk is deemed 4 or higher, including risk factors such as the following: HIV/AIDS, organ transplants (immunosuppressant use), silicosis, dialysis due to chronic renal failure, recent TB infection (within 2 years), fibronodular shadows in chest radiographs (untreated old TB), the use of biologics, and large doses of corticosteroids. Although the risk is lower, the following risk factors require consideration of LTBI treatment when 2 or more of them are present: use of oral or inhaled corticosteroids, use of other immunosuppressants, diabetes, being underweight, smoking, gastrectomy, and so on. In principle, INH is administered for a period of 6 or 9 months. When INH cannot be used, rifampicin is administered for a period of 4 or 6 months. It is believed that there are no reasons to support long-term LTBI treatment for immunosuppressed patients in Japan, where the risk of infection is not considered markedly high. For pregnant women, HIV-positive individuals, heavy drinkers, and individuals with a history of liver injury, regular liver function tests are necessary when treatment is initiated and when symptoms are present. There have been reports of TB developing during LTBI treatment; therefore, attention should be paid to TB development symptoms. When administering LTBI treatment, patients must be educated about side effects, the risk of developing TB onset, and the risks associated with discontinuing m

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; HIV Infections; Humans; Immunosuppressive Agents; Isoniazid; Japan; Latent Tuberculosis; Patient Education as Topic; Practice Guidelines as Topic; Rifampin; Risk Factors; Tuberculosis Societies

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

Topics: Antitubercular Agents; Ethambutol; Humans; Immune System Diseases; Isoniazid; Latent Tuberculosis; Liver; Liver Cirrhosis; Liver Diseases; Liver Failure; Liver Function Tests; Liver Transplantation; Prevalence; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant

Effective treatment of latent tuberculosis infection (LTBI) is an important component of TB elimination programs. Promising new regimens that may be more effective are being introduced. Because few regimens can be directly compared, network meta-analyses, which allow indirect comparisons to be made, strengthen conclusions.. To determine the most efficacious regimen for preventing active TB with the lowest likelihood of adverse events to inform LTBI treatment policies.. PubMed, EMBASE, and Web of Science up to 29 January 2014; clinical trial registries; and conference abstracts.. Randomized, controlled trials that evaluated LTBI treatment in humans and recorded at least 1 of 2 prespecified end points (preventing active TB or hepatotoxicity), without language or date restrictions.. Data from eligible studies were independently extracted by 2 investigators according to a standard protocol.. Of the 1516 articles identified, 53 studies met the inclusion criteria. Data on 15 regimens were available; of 105 possible comparisons, 42 (40%) were compared directly. Compared with placebo, isoniazid for 6 months (odds ratio [OR], 0.64 [95% credible interval {CrI}, 0.48 to 0.83]) or 12 months or longer (OR, 0.52 [CrI, 0.41 to 0.66]), rifampicin for 3 to 4 months (OR, 0.41 [CrI, 0.18 to 0.86]), and rifampicin-isoniazid regimens for 3 to 4 months (OR, 0.52 [CrI, 0.34 to 0.79]) were efficacious within the network.. The risk of bias was unclear for many studies across various domains. Evidence was sparse for some comparisons, particularly hepatotoxicity.. Comparison of different LTBI treatment regimens showed that various therapies containing rifamycins for 3 months or more were efficacious at preventing active TB, potentially more so than isoniazid alone. Regimens containing rifamycins may be effective alternatives to isoniazid monotherapy.. None.

Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Pyrazinamide; Rifampin

Latent tuberculosis infection (LTBI) refers to a circumstance in which viable Mycobacterium tuberculosis (MTB) bacilli are present in an individual but symptoms and signs of active disease are lacking, and the bacilli are relatively inactive metabolically. In favorable circumstances, some of these inactive bacilli resume greater metabolic activity and replication, leading to the development of active tuberculosis disease. Treatment of this condition (TLTBI) is designed to prevent (soon, or in the distant future) this progression from asymptomatic infection to symptomatic, potentially lethal, active disease. This narrative review draws upon recent reviews of LTBI and seeks particularly to include recently published or presented data that are not included in those prior reviews. Adverse effects of treatment are considered, as are the special circumstances of human immunodeficiency virus-related LTBI, drug resistance, and use of TLTBI in the context of tumor necrosis factor alpha (TNF-α) inhibition. The review describes the main studies underpinning Centers for Disease Control and Prevention recommendations on use of the new 3-month isoniazid-rifapentine regimen and points to evolving data that may support future modification of those recommendations.

Topics: Antitubercular Agents; Disease Progression; Drug Resistance, Bacterial; Drug Therapy, Combination; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; Tumor Necrosis Factor-alpha

Topics: Antitubercular Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifampin

Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to nine months has 60% to 90% protective efficacy, but the treatment period is long, liver toxicity is a problem, and completion rates outside trials are only around 50%. Rifampicin or rifamycin-combination treatments are shorter and may result in higher completion rates.. To compare the effects of rifampicin monotherapy or rifamycin-combination therapy versus INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB.. We searched the Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; clinical trials registries; regional databases; conference proceedings; and references, without language restrictions to December 2012; and contacted experts for relevant published, unpublished and ongoing trials.. Randomized controlled trials (RCTs) of HIV-negative adults and children at risk of active TB treated with rifampicin, or rifamycin-combination therapy with or without INH (any dose or duration), compared with INH for six to nine months.. At least two authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks (RRs) with their 95% confidence intervals (CIs), using a random-effects model if heterogeneity was significant. We assessed overall evidence quality using the GRADE approach.. Ten trials are included, enrolling 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years. Rifampicin (three/four months) vs. INH (six months)Five trials published between 1992 to 2012 compared these regimens, and one small 1992 trial in adults with silicosis did not detect a difference in the occurrence of TB over five years of follow up (one trial, 312 participants; very low quality evidence). However, more people in these trials completed the shorter course (RR 1.19, 95% CI 1.01 to 1.30; five trials, 1768 participants; moderate quality evidence). Treatment-limiting adverse events were not significantly different (four trials, 1674 participants; very low quality evidence), but rifampicin caused less hepatotoxicity (RR 0.12, 95% CI 0.05 to 0.30; four trials, 1674 participants; moderate quality evidence). Rifampicin plus INH (three months) vs. INH (six months)The 1992 silicosis trial did not detect a difference between people receiving rifampicin plus INH compared to INH alone for occurrence of active TB (one trial, 328 participants; very low quality evidence). Adherence was similar in this and a 1998 trial in people without silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence). Rifampicin plus pyrazinamide (two months) vs. INH (six months)Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving rifampicin plus pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed rifapentine plus INH (three months) vs. daily, self-administered INH (nine months)A large trial conducted from 2001 to 2008 am. Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens. Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens. Rifampicin combined with pyrazinamide is associated with more adverse events. A weekly regimen of rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.

Topics: Adult; Antibiotics, Antitubercular; Child; Directly Observed Therapy; Drug Administration Schedule; HIV Seronegativity; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifabutin; Rifampin; Tuberculosis, Pulmonary

Treatment of latent tuberculosis (TB) infection is an important component of TB control programs in both high- and low-prevalence countries. Clinical trials of treatment of latent TB conducted over several decades have demonstrated that preventive treatment can reduce the risk of developing active TB up to 90%. Although 9 months of daily, self-administered isoniazid has been the most widely used and recommended regimen for the treatment of latent infection, other regimens such as 3 months of daily isoniazid and rifampin, or 4 months of daily rifampin alone have also been recommended and used. Most recently, a 12-dose regimen of once-weekly isoniazid and rifapentine has been shown to be noninferior to 9 months of daily isoniazid in a large and well conducted clinical trial. Adoption of such a regimen on a large scale could have significant implications for TB elimination efforts.

Topics: Animals; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Time Factors; Tuberculosis

Latent tuberculosis infection is a key stage in the natural history of tuberculosis, and provides an important period where strategies to prevent the development of disease may be implemented. The treatment of latent tuberculosis infection is well described in many national guidelines. In this review, we attempt to help pneumonologists to implement these guidelines accurately and appropriately, prescribing preventive treatment when the benefit-risk ratio is optimal, providing treatment most safely, performing therapeutic education and incorporating preventive treatment into the full array of measures against tuberculosis.

Topics: Antitubercular Agents; Cost of Illness; Drug Combinations; Humans; Incidence; Isoniazid; Latent Tuberculosis; Medication Adherence; Rifampin; Treatment Outcome

Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin; Time Factors; Treatment Outcome; Tuberculin Test; Tuberculosis, Multidrug-Resistant

Much remains unknown about latent infection with Mycobacterium tuberculosis. Existing immunodiagnostic tools for this condition have various limitations, most importantly in their ability to predict disease. Randomised controlled trials have established protective efficacy of isoniazid therapy for 6-12 months among non-HIV-infected and HIV-infected subjects. While efficacy may reach 90%, acceptance and adherence to prolonged therapy are less than desired. Rifampicin plus pyrazinamide for 2 months, though efficacious, has been associated with excess hepatotoxicity in non-HIV-infected persons. Isoniazid plus rifampicin for 3 months has proven efficacy, but adverse effects may be more frequent than isoniazid or rifampicin monotherapy. Rifampicin monotherapy for 3-4 months is well tolerated, but efficacy data are currently limited, and concerns remain over possible selection of rifampicin-resistant mutants. For contacts of patients with multidrug-resistant tuberculosis, expert opinions differ on whether to treat with at least two drugs or just a fluoroquinolone, and for how long. With the existing diagnostic and treatment tools, efficacy of preventive therapy does not necessarily translate into field effectiveness. A targeted approach is required to maximise cost-effectiveness. Each geographic region needs to set its own priority after taking into account available scientific data and local circumstances.

Topics: Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Communicable Disease Control; Drug Design; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Mycobacterium tuberculosis; Patient Compliance; Pyrazinamide; Rifampin; Treatment Outcome

To determine the age-related risk of hepatotoxicity under currently recommended treatment regimens for latent tuberculosis (TB) infection (LTBI).. A systematic review of the MEDLINE and EMBASE databases (from database inception to 2008) was performed to determine the risk of isoniazid (INH) and/or rifampicin hepatotoxicity in LTBI treatment stratified by patient age. Study selection, study quality assessment and data extraction were performed using piloted proformas. Rate data were meta-analysed to generate summary rates with 95%CI within age-related subgroups using a random effects model.. Seven relevant studies (18,610 participants, including 115 cases of hepatotoxicity) met the selection criteria. The median rate of hepatotoxicity was 1.8% (range 0.07-11.9). On average, rates were higher among those aged ≥ 35 years (1.7%, 95%CI 1.4-2.2) than those aged <35 years (0.2%, 95%CI 0.1-0.3).. The rates of hepatotoxicity were low. Summary estimates of risks generated in this review can be used for counselling individuals for whom chemoprophylaxis is recommended. The use of INH for the treatment of LTBI is safe in older patients with clinical or biochemical monitoring.

Topics: Age Factors; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Risk Factors

About a third of the world's population has latent tuberculosis. In 2004, over 14 million people had active tuberculosis. Approximately 1.7 million people died from the infection. Over 80% of new cases diagnosed in 2004 were in people in Africa, South-East Asia, and Western Pacific regions.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent tuberculosis in people without HIV infection at high risk of developing tuberculosis? What are the effects of interventions to prevent tuberculosis in people without HIV infection at high risk of developing multidrug-resistant tuberculosis? What are the effects of different drug regimens in people with newly diagnosed pulmonary tuberculosis without HIV infection? What are the effects of different drug regimens in people with multidrug-resistant tuberculosis without HIV infection? What are the effects of low-level laser therapy in people with tuberculosis without HIV infection? Which interventions improve adherence to treatment in people with tuberculosis without HIV infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 31 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding pyrazinamide in chemotherapy regimens lasting up to 6 months; adding rifampicin to isoniazid regimens; benefits of different regimens; chemotherapy for less than 6 months; daily chemotherapy; direct observation treatment; intermittent chemotherapy for 6 months or longer; isoniazid; low-level laser therapy for pulmonary tuberculosis; regimens containing quinolones; rifampicin plus isoniazid; substituting rifampicin with ethambutol in the continuous phase; and support mechanisms for directly observed treatment.

Topics: Antitubercular Agents; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Low-Level Light Therapy; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).. The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.. PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.. ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020.

Topics: Adult; Antitubercular Agents; Cohort Studies; Diabetes Mellitus, Type 2; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifampin; Tanzania

Tuberculosis preventive therapy (TPT) is recommended for people with HIV infection, including during pregnancy. The effect of TPT exposure at conception and during pregnancy is poorly documented.. We report pregnancy outcomes among South African women with HIV enrolled in a randomized trial of 4 TPT regimens (two 3-month regimens, rifapentine/isoniazid [3HP] or rifampin/isoniazid [3HR], isoniazid for 6 months, or isoniazid continuously). Descriptive statistics and risk ratios were assessed to examine relationships between study regimens and outcomes.. 216/896 women (24%) conceived during the study. Women who conceived were younger (27.9 vs 31.3 years) and had higher mean CD4 counts (589.1 vs 536.7). The odds of pregnancy were higher in women in the rifamycin-isoniazid arms than those in the isoniazid arms (3HP: relative risk [RR] 1.73, P = 0.001; 3HR:RR 1.55, P = 0.017) despite increased contraceptive use compared with the standard 6H therapy. Thirty-four women became pregnant while taking preventive treatment (8 rifamycin and 26 isoniazid monotherapy). Pregnancy outcomes in these women were as follows: 17 (50%) mother/baby healthy, 3 (9%) spontaneous abortions, 6 (18%) elective abortions, 1 (3%) premature delivery, 2 (6%) neonatal deaths [1 rifamycin-isoniazid and 1 isoniazid], and 5 (15%) unknown.. Pregnancy was common in women who had received TPT and more frequent in women who had received rifamycin-isoniazid-based regimens.

Topics: Antitubercular Agents; Contraceptive Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant, Newborn; Isoniazid; Latent Tuberculosis; Pregnancy; Rifampin; Rifamycins; Tuberculosis

Screening for and treatment of latent tuberculosis (TB) in patients with end-stage kidney disease (ESKD) are recommended. However, there is limited evidence on safety and treatment completion in this population. The objective of the study is to evaluate three short-course rifamycin-based regimens for the treatment of latent TB in ESKD patients.. Study design and setting. This is a prospective, open label, randomized clinical trial, that will be conducted at seven teaching hospitals in Spain. Study population, randomization, and interventions. Consecutive adult patients with ESKD requiring treatment for a latent TB infection will be randomly allocated (1:1:1) to receive one of the three treatment regimens of the study: three months of daily isoniazid plus rifampicin (3HR); three months of once-weekly isoniazid plus rifapentine (3HP); or four months of daily rifampicin (4R). Participants will be followed regularly through pre-established visits and a blood test schedule from enrolment to a month after finishing the assigned treatment. Outcomes. The primary outcome will be treatment completion, while the secondary outcomes will be discontinuation of the assigned treatment due to adverse events, related or unrelated to the study treatment; definitive discontinuation of the assigned treatment because of adverse events related to the treatment of the study, and death. Sample size. Two hundred and twenty-five subjects (75 per arm) will be enrolled, which will enable the demonstration, if it exists, of an increase of 0.16 in treatment completion rates either in the 3HP or 4R arm with respect to the 3HR arm.. Results of this clinical trial will contribute to evidence-based recommendations on the management of latent TB infection in ESKD patients.. ClinicalTrials.gov identifier: NCT05021731.

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Prospective Studies; Randomized Controlled Trials as Topic; Rifampin

The successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion.. A pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial.. Ethics approval has been obtained from The National Health Service Health Research Authority (20/LO/1097). All participants will be required to provide written informed consent. We will share the results in peer-reviewed journals.. EudraCT 2020-004444-29.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rifampin; State Medicine; United Kingdom; Young Adult

Pregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy.. IMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics.. Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P < .001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg × hour/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (P < .001), resulting in lower AUCss (522 mg × hour/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or infants.. 3HP does not require dose adjustment in pregnancy. Rifapentine clearance is higher among women with HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tuberculosis prevention. The data support proceeding with larger safety-focused studies of 3HP in pregnancy.. ClinicalTrials.gov, NCT02651259.

Topics: Adult; Antitubercular Agents; Child; Drug Therapy, Combination; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Pregnancy; Pregnant Women; Rifampin; Tuberculosis

Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks.. An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded.. Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms.. In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment.. The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).

Topics: Adolescent; Adult; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; London; Male; Middle Aged; Pilot Projects; Rifampin; Self Administration; Treatment Outcome; Young Adult

Using QuantiFERON-TB Gold In-Tube (QFT-GIT) for monitoring tuberculosis (TB) and latent TB infection treatment effect is controversial. The present study aimed to evaluate the dynamic changes of interferon gamma (IFN-γ) levels along with latent TB infection treatment via a randomized controlled study.. A total of 910 participants treated with 8 weeks of once-weekly rifapentine plus isoniazid (group A), 890 treated with 6 weeks of twice-weekly rifapentine plus isoniazid (group B) and 818 untreated controls (group C) were followed for 2 years to track active TB development. QFT-GIT tests were repeated three times for all groups: before treatment (T0), at completion of treatment (T1) and 3 months after completion of treatment (T2).. Similar rates of persistent QFT-GIT reversion were observed in groups A (19.0%, 173/910), B (18.5%, 165/890) and C (20.7%, 169/818) (p 0.512). The dynamic changes of IFN-γ levels were not statistically significant among the three groups. In treated participants, individuals with higher baseline IFN-γ levels showed increased TB occurrence (1.0%, 9/896) compared to those with lower baseline levels (0.2%, 2/904) (p 0.037). A similar but statistically insignificant trend was also observed in untreated controls (1.8% (7/400) vs. 0.5% (2/418), p 0.100). When TB cases were matched with non-TB cases on baseline IFN-γ levels, no significant differences were found with respect to the dynamic changes in IFN-γ levels with time, regardless of whether they received treatment.. QFT-GIT reversion or decreased IFN-γ levels should not be used for monitoring host response to latent TB infection treatment.

Topics: Antitubercular Agents; Biomarkers; China; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Interferon-gamma; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Rifampin; Treatment Outcome

Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen.. To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid.. Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209).. High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea).. Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection.. Health system costs per participant.. A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population.. Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines.. A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection.. Canadian Institutes of Health Research.

Topics: Adult; Antitubercular Agents; Child; Costs and Cost Analysis; Developed Countries; Developing Countries; Drug Administration Schedule; Female; Health Care Costs; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin

To investigate treatment outcomes and associated characteristics of persons experiencing homelessness who received 12-weekly doses of directly observed isoniazid and rifapentine (3HP/DOT) treatment for latent TB infection (LTBI).. Among homeless persons treated with 3HP/DOT during July 2011 -June 2015 in 11 U.S. TB programs, we conducted descriptive analyses of observational data, and identified associations between sociodemographic factors and treatment outcomes. Qualitative interviews were conducted to understand programmatic experiences.. Of 393 persons experiencing homelessness (median age: 50 years; range: 13-74 years), 301 (76.6%) completed treatment, 55 (14.0%) were lost to follow-up, 18 (4.6%) stopped because of an adverse event (AE), and 19 (4.8%) stopped after relocations or refusing treatment. Eighty-one (20.6%) had at least one AE. Persons aged ≥65 were more likely to discontinue treatment than persons aged 31-44 years. Programs reported difficulty in following up with persons experiencing homelessness because of relocations, mistrust, and alcohol or drug use.. This study demonstrates the feasibility of administering the 3HP/DOT LTBI regimen to persons experiencing homelessness, a high-risk population.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Ill-Housed Persons; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Rifampin; United States

Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.. We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.. A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).. A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).

Topics: Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Rifampin; Tuberculosis

Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy.. To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H).. Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date.. Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively.. Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).

Topics: Adolescent; Adult; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Isoniazid; Latent Tuberculosis; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Rifampin; Young Adult

Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection. This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication.. This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once daily alone (days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (days 5-19). Dolutegravir concentrations were measured on days 4, 14, and 19, and rifapentine, 25-desacetyl-rifapentine, and isoniazid concentrations were measured on day 19. Cytokines and antidrug antibodies to isoniazid and rifapentine were examined at select time points.. The study was terminated following the development of flu-like syndrome and elevated aminotransferase levels in 2 of 4 subjects after the third isoniazid-rifapentine dose. Markedly elevated levels of interferon-γ, CXCL10, C-reactive protein, and other cytokines were temporally associated with symptoms. Antidrug antibodies were infrequently detected. Dolutegravir area under the curve (AUC) was decreased by 46% (90% confidence interval, 27-110%; P = .13) on day 14. Rifapentine and 25-desacetyl rifapentine levels on day 19 were comparable to reference data, whereas isoniazid AUCs were approximately 67%-92% higher in the subjects who developed toxicities.. The combined use of dolutegravir with once-weekly isoniazid-rifapentine resulted in unexpected and serious toxicities that were mediated by endogenous cytokine release. Additional investigations are necessary to examine the safety and efficacy of coadministering these medications.. NCT02771249.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Cytokines; Drug Administration Schedule; Drug Interactions; Female; Healthy Volunteers; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Rifampin; Young Adult

There is limited high-quality evidence available to inform the use of text messaging to improve latent tuberculosis infection (LTBI) treatment adherence.We performed a parallel, randomised controlled trial at two sites to assess the effect of a two-way short message service on LTBI adherence. We enrolled adults initiating LTBI therapy from June 2012 to September 2015 in British Columbia, Canada. Participants were randomised in a 1:1 ratio to standard LTBI treatment (control) or standard LTBI treatment plus two-way weekly text messaging (intervention). The primary outcome was treatment completion, defined as taking ≥80% prescribed doses within 12 months (isoniazid) or 6 months (rifampin) of enrolment. The trial was unblinded except for the data analyst.A total of 358 participants were assigned to the intervention (n=170) and control (n=188) arms. In intention-to-treat analysis, the proportion of participants completing LTBI therapy in the intervention and control arms was 79.4% and 81.9%, respectively (RR 0.97, 95% CI 0.88-1.07; p=0.550). Results were similar for pre-specified secondary end-points, including time-to-completion of LTBI therapy, completion of >90% of prescribed LTBI doses and health-related quality of life.Weekly two-way text messaging did not improve LTBI completion rates compared to standard LTBI care; however, completion rates were high in both treatment arms.

Topics: Adult; Antitubercular Agents; British Columbia; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Quality of Life; Rifampin; Text Messaging; Treatment Adherence and Compliance

Treatment of latent tuberculosis (TB) infection (LTBI) effectively prevents its progression to active TB. However, long treatment duration and drug-related hepatotoxicity limit the effectiveness of the 9-month daily isoniazid (9H). Data on the 3-month weekly rifapentine plus isoniazid (3 HP) in Asian populations are currently unavailable. We prospectively randomised the LTBI contacts aged ≥12 years with positive tuberculin skin test into 9H and 3 HP groups in four hospitals between January 2014 and May 2016 in Taiwan. The primary and secondary outcomes were treatment completion rate and adverse drug reactions (ADRs), respectively. Overall, 263 participants with LTBI were randomised into the 3 HP (n = 132) and 9H groups (n = 131); 14 (10.6%) and 29 (22.1%) participants in the 3 HP and 9H groups, respectively, discontinued therapy (p = 0.011). Discontinuation rates owing to ADRs were 9.1% (3 HP) and 5.3% (9H) (p = 0.241). Clinically relevant hepatotoxicity was more common in the 9H than in the 3 HP group (5.3% vs. 1.5%; p = 0.103), whereas systemic drug reaction was more common in the 3 HP than in the 9H group (3.8% vs. 0%; p = 0.060). Women had a significantly higher rate of Grade II fever than men (13.7% vs. 1.2%; p = 0.003). Compared with the 9H regimen, the 3 HP regimen had a higher completion rate with lower hepatotoxicity and well-tolerated ADR.. number NCT02208427.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Child; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Prospective Studies; Rifampin; Taiwan; Time Factors; Treatment Outcome; Young Adult

The treatment of latent infection with Mycobacterium tuberculosis is important in children because of their vulnerability to life-threatening forms of tuberculosis disease. The current standard treatment - 9 months of isoniazid - has been associated with poor adherence and toxic effects, which have hampered the effectiveness of the drug. In adults, treatment with 4 months of rifampin has been shown to be safer and to have higher completion rates than 9 months of isoniazid.. In this multicenter, open-label trial, we randomly assigned 844 children (<18 years of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that resulted in the permanent discontinuation of a trial drug. Secondary outcomes were treatment adherence, side-effect profile, and efficacy. Independent review panels whose members were unaware of trial-group assignments adjudicated all adverse events and progression to active tuberculosis.. Of the children who underwent randomization, 829 were eligible for inclusion in the modified intention-to-treat analysis. A total of 360 of 422 children (85.3%) in the rifampin group completed per-protocol therapy, as compared with 311 of 407 (76.4%) in the isoniazid group (adjusted difference in the rates of treatment completion, 13.4 percentage points; 95% confidence interval [CI], 7.5 to 19.3). There were no significant between-group differences in the rates of adverse events, with fewer than 5% of the children in the combined groups with grade 1 or 2 adverse events that were deemed to be possibly related to a trial drug. Active tuberculosis, including 1 case with resistance to isoniazid, was diagnosed in 2 children in the isoniazid group during 542 person-years of follow-up, as compared with no cases in the rifampin group during 562 person-years (rate difference, -0.37 cases per 100 person-years; 95% CI, -0.88 to 0.14).. Among children under the age of 18 years, treatment with 4 months of rifampin had similar rates of safety and efficacy but a better rate of adherence than 9 months of treatment with isoniazid. (Funded by the Canadian Institutes of Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number, NCT00170209 .).

Topics: Adolescent; Antibiotics, Antitubercular; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Intention to Treat Analysis; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Patient Safety; Rifampin; Treatment Outcome

A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects.. In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels.. Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events.. The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Rifampin

Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organization's End TB Strategy.In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50-69 years with LTBI in China.Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). In the modified intention-to-treat analysis on the completed doses, the cumulative rate of active disease during 2 years of follow-up was 1.21% (14 out of 1155) in the untreated controls, 0.78% (10 out of 1284) in the group that received the 8-week once-weekly regimen and 0.46% (six out of 1299) in the group that received the 6-week twice-weekly regimen. The risk of active disease was decreased, with an adjusted hazard ratio of 0.63 (95% CI 0.27-1.43) and 0.41 (95% CI 0.15-1.09) for the treatments, respectively. No significant difference was found in the occurrence of hepatotoxicity (1.02% (13 out of 1279)

Topics: Aged; Antibiotics, Antitubercular; China; Communicable Disease Control; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Proportional Hazards Models; Rifampin; Risk Factors; Rural Population; Treatment Outcome

Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation.. To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation.. An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711).. Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa.. 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection.. Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring.. The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event-monitoring devices for self-administration. The main secondary outcome was adverse events.. Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups.. Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically.. These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible.. Centers for Disease Control and Prevention.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Directly Observed Therapy; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Reminder Systems; Rifampin; Self Administration; Text Messaging

Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain.. Cost-analysis of standard and short-course therapy for LTBI in an Australian context.. Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine.. Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01).. This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Australia; Cost-Benefit Analysis; Disease Eradication; Drug Administration Schedule; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; New Zealand; Prospective Studies; Rifampin; Self Administration; Young Adult

The objective of this prospective study was to evaluate the diagnosis and treatment of latent tuberculosis infection (LTBI) in adult close contacts of active pulmonary tuberculosis (TB) patients in Korea.. Adult close contacts of active pulmonary TB patients were recruited at a regional tertiary hospital in Korea. The participants were tested for LTBI using the tuberculin skin test (TST) and/or QuantiFERON-TB Gold (QFT-G) test. LTBI patients, who consented to treatment, were randomly assigned to receive isoniazid for 9 months (9INH) or rifampin for 4 months (4RIF).. We examined 189 adult close contacts (> 18 years) of 107 active pulmonary TB patients. The TST and QFT-G were positive (≥ 10 mm) in 75/183 (39.7%) and 45/118 (38.1%) tested participants, respectively. Among 88 TST or QFT-G positive LTBI participants, 45 participants were randomly assigned to receive 4RIF (n = 21) or 9INH (n = 24), respectively. The average treatment duration for the 4RIF and 9INH groups was 3.3 ± 1.3 and 6.1 ± 2.7 months, respectively. Treatment was completed in 25 participants (4RIF, n = 16; 9INH, n = 9). LTBI participants who accepted treatment were more likely to be women and have more cavitary lesions on the chest radiographs of index cases and positive TST and QFT-G results compared to those who refused treatment.. About 40% of adult close contacts of active pulmonary TB patients had LTBI; about 50% of these LTBI participants agreed to treatment.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Contact Tracing; Drug Administration Schedule; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Predictive Value of Tests; Prospective Studies; Republic of Korea; Rifampin; Tertiary Care Centers; Time Factors; Treatment Outcome; Tuberculin Test; Tuberculosis, Pulmonary; Young Adult

Tuberculosis reactivation is a serious threat in patients treated with anti-tumour necrosis factor therapy. A 6-month regimen with isoniazid is considered as the standard of care, but patient adherence is a major shortcoming. We carried out an open-label, single-arm intervention study to assess the efficacy, the completion rate and the tolerability of a 3-month regimen with isoniazid plus rifampin. Seventy-eight patients with rheumatic conditions proposed for anti-tumour necrosis factor (TNF) therapy and at risk of tuberculosis reactivation were offered to participate in the study. Nine patients were excluded due to deficit of glucose-6-phosphate dehydrogenase (n = 1), salicylate hypersensitivity (n = 1), declining to participate (n = 5) or preferring a 6-month isoniazid regimen (n = 6). Sixty-nine patients were treated with a 3-month regimen with isoniazid and rifampin. No cases of tuberculosis were observed after a mean follow-up of 90 months (range from 66 to 121 months). Sixty (87 %) patients completed the therapy. Nine (13 %) patients discontinued the therapy due to rifampin hypersensitivity (n = 1), symptomatic grade 3-4 hepatotoxicity (n = 2), abdominal discomfort (n = 2), pruritus (n = 1), arthritis (n = 1) and personal concerns (n = 2). A short course treatment with isoniazid and rifampin provided efficacy, good tolerability and good completion rate in patients with rheumatic conditions proposed for anti-TNF therapy.

Topics: Adult; Aged; Antirheumatic Agents; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Rheumatic Diseases; Rifampin; Treatment Outcome; Tumor Necrosis Factor-alpha

Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited.. To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children.. A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection.. Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months.. We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%.. Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of -0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion.. Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe.. clinicaltrials.gov Identifier: NCT00023452.

Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin; Treatment Outcome

Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome.. We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study.. Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1).. SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.. NCT00023452.

Topics: Adolescent; Adult; Antitubercular Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Prospective Studies; Respiratory Tract Diseases; Rifampin

Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear.. To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity.. Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV.. Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors.. The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

Topics: Adult; Antitubercular Agents; Aspartate Aminotransferases; Brazil; Canada; Case-Control Studies; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Therapy, Combination; Female; Hepatitis C; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Multivariate Analysis; Rifampin; Risk Factors; Spain; United States

To compare the tolerance, adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection (LTBI): 6 months of isoniazid (6H) vs. 3 months of isoniazid plus rifampicin (3RH).. Immigrants with LTBI.. Participants were enrolled in a controlled, randomised clinical trial in Barcelona, Spain, from April 2001 to April 2005. Monthly follow-up was done to assess tolerance, side effects and adherence. Effectiveness was evaluated at 5 years.. In the 590 subjects enrolled, the rate of adherence was greater in the 3RH than in the 6H arm (72% vs. 52.4%, P = 0.001). No differences between study arms were observed with respect to hepatotoxicity or side effects. Variables associated with non-adherence were diagnosis by screening (OR 1.88, 95%CI 1.26-2.82, P = 0.001), illegal immigration status (OR 1.48, 95%CI 1.01-2.15, P = 0.03), unemployment (OR 1.91, 95%CI 1.28-2.85, P = 0.0008), illiteracy (OR 1.73, 95%CI 1.04-2.88, P = 0.02), lack of family support (OR 3.7, 95%CI 2.54-5.4, P = 0.001) and the 6-month treatment regimen (OR 2.45, 95%CI 1.68-3.57, P = 0.0001). None of the patients who completed either treatment developed tuberculosis.. The 3RH regimen facilitates adherence to LTBI treatment and offers a safe, well-tolerated and effective alternative.

Topics: Adolescent; Adult; Antitubercular Agents; Chi-Square Distribution; Child; Drug Administration Schedule; Emigrants and Immigrants; Female; Humans; Isoniazid; Latent Tuberculosis; Logistic Models; Male; Medication Adherence; Multivariate Analysis; Odds Ratio; Prevalence; Prospective Studies; Rifampin; Risk Assessment; Risk Factors; Socioeconomic Factors; Spain; Time Factors; Treatment Outcome; Young Adult

Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil.. To compare QuantiFERON®-TB Gold In-Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens.. Participants in the trial were invited to undergo serial QFT-GIT. Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points.. Of 215 participants, 118 completed treatment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant difference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non-adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment.. Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions.

Topics: Adult; Antitubercular Agents; Brazil; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Rifampin; Time Factors; Treatment Outcome; Tuberculin Test; Young Adult

Topics: Adolescent; Adult; Antibiotics, Antitubercular; Antitubercular Agents; Apolipoproteins A; Apolipoproteins B; Biomarkers; Female; Humans; Isoniazid; Latent Tuberculosis; Lipid Metabolism; Lipids; Male; Middle Aged; Rifampin; Young Adult

A prison in northern Taiwan.. To compare safety and the completion rate of the 4-month daily rifampicin regimen (4R) vs. the standard 6-month daily isoniazid regimen (6H) for latent tuberculosis infection (LTBI) in prison inmates.. This was an open-label randomised trial among human immunodeficiency virus negative male inmates. Inmates without active tuberculosis (TB) who tested positive for both the tuberculin skin test and QuantiFERON®-TB Gold In-Tube were eligible, but those with baseline glutamic pyruvic transaminase (GPT) levels ≥ 120 U/l, bilirubin levels ≥ 2.4 U/l or a platelet count < 150 k/mm(3) were excluded. The primary endpoint was any adverse event that resulted in discontinuation of LTBI treatment.. Participants (n = 373; 14% hepatitis B surface antigen positive, 21% anti-hepatitis C virus [HCV] positive) were randomised (stratified by hepatitis B virus, HCV status and 2-year prison term) to receive either 4R or 6H under directly observed treatment. The 4R group (n = 190) was less likely to experience an adverse event leading to discontinuation of treatment (2% vs. 12%, P < 0.001 for all adverse events; 0% vs. 8%, P < 0.001 for hepatotoxicity), and more likely to complete LTBI treatment (86% vs. 78%, P = 0.041), compared with the 6H group (n = 183).. 4R is safer and has a higher completion rate than 6H as treatment for LTBI among male prison inmates.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Follow-Up Studies; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Prisoners; Rifampin; Taiwan; Treatment Outcome; Tuberculin Test; Young Adult

This open-label randomized trial compared isoniazid (9 months) to rifampin (4 months) on toxicity and completion in a jailed population with latent tuberculosis infection. Rifampin resulted in fewer elevated liver function tests (risk ratio [RR] 0.39, 95% confidence interval [CI] [0.18, 0.86]) and less toxicity requiring medication withdrawal (RR 0.51, 95% CI [0.13, 2.01]), although one participant receiving rifampin experienced an allergic reaction. Completion was achieved for 33% receiving rifampin compared to 26% receiving isoniazid (p = .10). With careful monitoring rifampin is a safe and less toxic regimen and appears to be a reasonable alternative because of its shorter duration, allowing more people to complete treatment behind bars. Therapy completion in released inmates is unacceptably low and ensuring follow-up after discharge must be part of a decision to treat.

Topics: Adult; Antitubercular Agents; Directly Observed Therapy; Female; Humans; Isoniazid; Latent Tuberculosis; Liver Function Tests; Male; Medication Adherence; Prisons; Rifampin; Socioeconomic Factors

Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain.. To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP.. A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada.. With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is ≥75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost.. 4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings.

Topics: Adult; Antitubercular Agents; Brazil; Canada; Cost-Benefit Analysis; Decision Support Techniques; Drug Administration Schedule; Drug Costs; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Models, Economic; Research Design; Rifampin; Saudi Arabia; Time Factors; Treatment Outcome; Young Adult

Randomised controlled trial of latent tuberculosis infection (LTBI) treatment in 10 clinics in Canada, Saudi Arabia and Brazil.. To identify early predictors of LTBI treatment adherence, including pre-treatment characteristics.. Patients randomised to 4 months of rifampicin (RMP; n = 420) or 9 months of isoniazid (n = 427) were monitored for adherence using an electronic device. Outcomes were 1) treatment completion, defined as intake of >or=80% of the prescribed doses, and further categorised as completed within the allotted time or not; and 2) treatment regularity, measured by the time interval between doses. Relative risk (RR) and adjusted odds ratios (aOR) of patients' pre-treatment characteristics and adherence at first follow-up visit were calculated.. Completion of treatment was higher with RMP (aOR 4.3, 95%CI 2.7-6.8). Early predictors (first follow-up visit) of non-adherence were late first visit attendance (RR for completion in time 0.9, 95%CI 0.8-0.98), >20% of missed doses (RR 0.4, 95%CI 0.3-0.6) and greater variation of hours between doses (0.209 vs. 0.131, P < 0.001). Serious adverse events were not associated with irregularity of treatment.. The shorter RMP regimen was associated with better adherence. Patients with poor adherence could be identified at the first follow-up visit from their punctuality in follow-up, missed doses and variability of pill-taking.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Brazil; Canada; Female; Follow-Up Studies; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Prospective Studies; Rifampin; Risk; Saudi Arabia; Time Factors; Young Adult

Treatment for latent tuberculosis infection with isoniazid for 9 months (9INH) has poor completion and serious adverse events, while treatment for 4 months with daily rifampin (4RIF) has significantly higher completion and fewer adverse events.. To compare the health system costs of 4RIF and 9INH.. In a randomised trial conducted in five Canadian centres, one Brazilian and one Saudi Arabian centre, consenting subjects were randomised to receive 4RIF or 9INH. Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits, investigations and drugs. All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute. Costs were expressed in Canadian dollars.. Total health system cost per patient allocated to 4RIF was $854 compared with $970 for 9INH (p<0.0001). The average cost per patient for the 328 of 420 (78%) who completed 4RIF therapy was $1094 compared with $1625 for the 254 of 427 (60%) completing 9INH (p<0.0001). Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events. Total costs related to management of adverse events with 9INH were $48 142 compared with $25 684 for 4RIF (p=0.008). Using these data, incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74%, and cost saving if efficacy exceeded 65%.. The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.

Topics: Adult; Antibiotics, Antitubercular; Brazil; Canada; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Health Care Costs; Health Services; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Saudi Arabia

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.. 对结核潜伏感染者开展预防性治疗可减少感染人群发生结核病的机会，是控制结核病的一项重要措施。我国推荐对部分重点人群的结核潜伏感染者开展预防性治疗，从而减少结核病发病的风险。耐多药/利福平耐药结核病患者接触者感染耐药病原体的风险高，但是目前对于接触耐多药/利福平耐药结核病患者的感染者还没有推荐的预防性治疗方案，本文检索文献、指南、专家共识和技术规范，对目前耐多药/利福平耐药结核病患者接触者预防性治疗方案和保护效果进行综述，为结核潜伏感染防控提供参考依据。.

Topics: Antitubercular Agents; China; Humans; Latent Tuberculosis; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

To evaluate implementation of rifamycin-based regimens (RBR) for pediatric tuberculosis infection (TBI) treatment among 3 provider settings in a high-incidence county.. A multicenter, retrospective observational study was performed across 3 sites in Los Angeles County: an academic center (AC), a general pediatrics federally qualified health center (FQHC), and department of public health (DPH) tuberculosis clinics. Patients initiated on TBI treatment age 1 months to 17 years between 2018 and 2020 were included. RBRs were defined as regimens: 3 months of weekly rifapentine and isoniazid, 4 months of daily rifampin, and 3 months of daily isoniazid and rifampin.. We included 424 patients: 51 from AC, 327 from DPH, and 46 from FQHC. RBR use nearly doubled during the study period (from 43% in 2018 to 82% in 2020; P < .001). FQHC had the shortest time to chest radiograph and treatment initiation; however, AC and DPH were 4 times as likely to prescribe an RBR compared to FQHC (95% CI, 2.1-7.8). AC and DPH had similar completion rates (74%) and were 2.6 times as likely to complete treatment compared to FQHC (95% CI, 1.4-4.9).. The use of RBRs for pediatric TBI varies significantly by clinical setting but is improving over time. Strategies are needed to improve RBR uptake, standardize care, and increase treatment completion, particularly among general pediatricians.

Topics: Antitubercular Agents; Child; Drug Therapy, Combination; Humans; Infant; Isoniazid; Latent Tuberculosis; Pediatrics; Rifampin; Tuberculosis

Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups.. We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations.. Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT.. TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Topics: Cross-Sectional Studies; HIV Infections; Humans; Incidence; Latent Tuberculosis; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have antituberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI formulations for TPT. We used a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations. This work identified several LAI-like exposure profiles of rifapentine and rifabutin that, if achieved by LAI formulations, could be efficacious as TPT regimens and thus can serve as experimentally determined targets for novel LAI formulations of these drugs. We present novel methodology to understand the exposure-response relationship and inform the value proposition for investment in development of LAI formulations that have utility beyond latent tuberculosis infection.

Topics: Animals; Antitubercular Agents; Latent Tuberculosis; Mice; Rifabutin; Rifampin

Topics: Humans; Latent Tuberculosis; Rifampin; Risk Factors

Topics: Humans; Latent Tuberculosis; Patients; Rifampin; Shock; Tuberculosis

We present a case of a 53-year-old person living with human immunodeficiency virus and a new diagnosis of latent tuberculosis. The patient had baseline suppressed HIV viral load on fixed dose combination dolutegravir/abacavir/lamivudine when once-weekly rifapentine 900 mg/isoniazid 900 mg/pyridoxine 25 mg was initiated for 12 weeks. An additional 50 mg dolutegravir dose, administered in the evenings, was added to the daily antiretroviral regimen for treatment duration secondary to rifapentine uridine diphosphate glucuronsyl transferase induction. Dolutegravir trough concentrations decreased during concurrent therapy with noted slight HIV viral load rebound. Upon completion of rifapentine use, and a return to dolutegravir 50 mg daily dose, the trough concentrations increased with a return to an undetectable viral load. We provide suggested dolutegravir dosing considerations with concomitant rifapentine use, not currently addressed in recommended guidelines.

Topics: Anti-HIV Agents; Drug Therapy, Combination; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Rifampin

Topics: Humans; Latent Tuberculosis; Patients; Rifampin; Shock; Tuberculosis

Screening and treatment of latent tuberculosis infections (LTBI) are required before starting biologics in patients with immune-mediated inflammatory diseases (IMIDs). This study aimed to assess the safety of LTBI treatment in older patients with IMIDs.. The medical records of 916 patients treated for LTBI before the start of biologics for IMIDs between January 2004 and December 2018 were reviewed. The safety profiles of LTBI treatment were retrospectively compared according to age.. Among the 916 patients, 201 were aged > 60 years (older age group). The older age group showed female predominance, more frequent history of previous tuberculosis, and more comorbidities, and received biologics mainly for rheumatoid arthritis. Most patients (74.0%) took isoniazid and rifampicin daily for 3 months. The treatment completion rate was 90.4% in the overall population and was lower in the older age group (91.9% vs. 85.1%, P = 0.005). Adverse drug events were more frequent in the older age group (22.9% vs. 9.8%, P < 0.001); however, differences were mainly observed for nausea (5.5% vs. 2.1%, P = 0.016) and flu-like syndrome (6.5% vs. 1.7%, P = 0.001), but not hepatotoxicity.. LTBI treatment is generally safe in older patients with IMIDs, especially with respect to hepatotoxicity. Key points • The older age group had significantly more nausea and flu-like syndrome but not hepatotoxicity, compared to the younger age group. • LTBI treatment was acceptable and generally safe in the older age group.

Topics: Aged; Antitubercular Agents; Female; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Retrospective Studies; Rifampin; Tuberculosis

Topics: Antitubercular Agents; Drug Interactions; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Systemic drug reaction (SDR) is a major safety concern with weekly rifapentine plus isoniazid for 12 doses (3HP) for latent tuberculosis infection (LTBI). Identifying SDR predictors and at-risk participants before treatment can improve cost-effectiveness of the LTBI program.. We prospectively recruited 187 cases receiving 3HP (44 SDRs and 143 non-SDRs). A pilot cohort (8 SDRs and 12 non-SDRs) was selected for generating whole-blood transcriptomic data. By incorporating the hierarchical system biology model and therapy-biomarker pathway approach, candidate genes were selected and evaluated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Then, interpretable machine learning models presenting as SHapley Additive exPlanations (SHAP) values were applied for SDR risk prediction. Finally, an independent cohort was used to evaluate the performance of these predictive models.. Based on the whole-blood transcriptomic profile of the pilot cohort and the RT-qPCR results of 2 SDR and 3 non-SDR samples in the training cohort, 6 genes were selected. According to SHAP values for model construction and validation, a 3-gene model for SDR risk prediction achieved a sensitivity and specificity of 0.972 and 0.947, respectively, under a universal cutoff value for the joint of the training (28 SDRs and 104 non-SDRs) and testing (8 SDRs and 27 non-SDRs) cohorts. It also worked well across different subgroups.. The prediction model for 3HP-related SDRs serves as a guide for establishing a safe and personalized regimen to foster the implementation of an LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.

Topics: Antitubercular Agents; Decision Support Techniques; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Isoniazid; Latent Tuberculosis; Rifampin

We aimed to determine if offering a 12-dose once-weekly treatment (3HP) as an additional treatment option would result in an increase in the overall proportion of patients completing TB preventive treatment (TPT) above the baseline rate.. We analyzed outcomes in consecutive adults referred to a TB clinic from January 2010 to May 2019. Starting December 2016, 3HP was offered as an alternative to standard clinic regimens which included 9 months of daily isoniazid or 4 months of daily rifampin. The primary outcome was the proportion of patients who completed TPT among all patients who started treatment. Using segmented autoregression analysis, we compared completion at the end of the study with projected completion had the intervention not been introduced.. A total of 2803 adults were referred for assessment over the study period. There was an absolute increase in completions among those who started a treatment of 19.0% at the end of the study between the observed intervention completion rate and the projected completion rate from the baseline study period (the completion rate had the 3HP intervention not been introduced) (76% observed vs 57% projected; 95% CI 6.6 to 31.4%; p = 0.004) and an absolute increase among those who were offered treatment (17.3%; 95% CI, 2.3 to 32.3%; p = 0.025).. The introduction of 3HP for TPT as an alternative to the regular regimens offered resulted in a significant increase in the proportion of patients completing treatment. Our study provides evidence to support accelerated use of 3HP in Canada.

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Humans; Interrupted Time Series Analysis; Isoniazid; Latent Tuberculosis; Rifampin

Household contact (HHC) investigation is an important strategy to identify individuals with tuberculosis (TB) exposure, infection and disease, including those who may benefit from tuberculosis preventive therapy (TPT). Data in children exposed to rifampin-resistant TB are limited.. In preparation for and to inform the feasibility of an interventional trial, HHC of adults with pulmonary rifampin-resistant TB from high TB-burden countries were evaluated in a cross-sectional study. Using interferon-gamma release assay and study-specific and 2015 international consensus definitions of intrathoracic TB in children, we evaluated the prevalence and predictors of TB infection and disease in child (<15 years) HHCs.. Of 303 child HHCs, median age (range) 7 years (0-14), 57% [95% confidence interval (CI): 50%-64%] had a positive interferon-gamma release assay result (TB infected). TB infection was associated with the index case smoking (P = 0.034), being the parent or sleeping in the same room (P = 0.002) and the child HHC being age ≥5 years and having attended school (P = 0.013). Four had study-defined confirmed TB and 9 had probable TB, a prevalence of 4.3% (95% CI: 2.6%-7.1%). Using the international consensus definitions, 4 had confirmed TB and 49 had unconfirmed TB, a prevalence of 17.2% (95% CI: 12.9%-22.4%). Twenty (7%) children had received TPT.. The prevalence of TB infection and disease was high in child HHC exposed to rifampin-resistant TB. Few children had routinely received TPT. High-quality evidence is needed to inform strong recommendations for and access to TPT in children exposed to TB resistant to rifampin.

Topics: Adult; Child; Child, Preschool; Cross-Sectional Studies; Humans; Latent Tuberculosis; Prevalence; Rifampin; Tuberculosis; Tuberculosis, Pulmonary

Some biologics for psoriasis, especially anti-tumor necrosis factor (TNF)-α therapies, may re-activate latent tuberculosis (TBC) infection with consequent morbidity and mortality. However, there is a low reported incidence of conversion to positive TBC status among patients with psoriasis treated with second-generation biologic therapies, particularly anti-interleukin (IL)-17 therapies such as secukinumab.. To evaluate the safety profile of secukinumab in psoriasis patients with latent TBC infection.. Real-life data were collected by retrospective chart review on patients with moderate-to-severe psoriasis who showed positivity for TBC screening at baseline and underwent secukinumab treatment for psoriasis at six Italian centers. Patients received secukinumab 300 mg at week 0/1/2/3/4, then every 4 weeks.. Fifty-nine patients were enrolled; 30.5% also had psoriatic arthritis and other comorbidities were common. At baseline, the mean psoriasis duration was 14.5 years. Ten (17%) patients did not undergo prophylaxis before starting secukinumab. Conversely, isoniazid ± rifampicin or rifampicin alone prophylaxis was administered in 49/59 (83.1%) patients. After a mean treatment duration of 84 weeks, there were no cases of TBC reactivation and no unexpected safety signals.. Secukinumab use over an extended period was safe in psoriasis patients with latent TBC, even in patients who did not receive chemoprophylaxis.

Topics: Antibodies, Monoclonal, Humanized; Humans; Isoniazid; Latent Tuberculosis; Psoriasis; Retrospective Studies; Rifampin; Severity of Illness Index; Treatment Outcome; Tuberculosis

A significant drop in tuberculosis (TB) case-finding has been widely reported during the period of the COVID-19 pandemic. To address a decrease in TB notification, Belarus introduced laboratory TB testing in patients with the laboratory-confirmed coronavirus disease 2019 (COVID-19). We conducted a secondary analysis of health records among 844 patients with laboratory-confirmed COVID-19 diagnosis who were admitted to repurposed departments at TB hospitals and who were tested by Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) in five Belarus regions between April and October 2021. Quantitative analysis followed by 13 individual interviews with health managers, physicians, and nurses participating in the intervention. Most patients were male (64%) and mean age was 43.5 ± 16 years. One in twenty (n = 47, 5.6%) patients were co-infected with active pulmonary TB, and over one-third of them (n = 18) had rifampicin resistance. In-hospital mortality was comparable in patients with and without TB co-infection (2.1% and 2.3% respectively, p > 0.99). Laboratory TB testing among patients with COVID-19 at repurposed departments of TB hospitals is feasible in Belarus and may improve TB case-finding.

Topics: Adult; Antibiotics, Antitubercular; Coinfection; COVID-19; COVID-19 Testing; Hospitalization; Humans; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Pandemics; Republic of Belarus; Rifampin; Sensitivity and Specificity; Tuberculosis

In 2017, Korea implemented nationwide latent tuberculosis infection (LTBI) project targeting healthcare workers (HCWs). We aimed to assess its performance using the cascade of care model.. We included 45,503 employees of medical institutions with positive interferon-gamma release assay result who participated between March 2017 and December 2018. We described percentages of LTBI participants completing each step in the cascade of care. Poisson regression model was conducted to assess individual characteristics and factors associated with not-visiting clinics for further care, not-initiating LTBI treatment, and not-completing treatment.. Proportions of visiting clinics and initiating and completing treatment in HCWs were 54.9%, 38.5%, and 32.0%, respectively. Despite of less likelihood of visiting clinics and initiating LTBI treatment, older age ≥ 65 years were more likely to complete treatment (adjusted relative risk [aRR], 0.80; 95% confidence interval [CI], 0.64-0.99), compared to young age < 35 years. Compared to nurses, doctors were less likely to visit clinic; however, were more likely to initiate treatment (aRR, 0.88; 95% CI, 0.81-0.96). Those who visited public health centers were associated with not-initiating treatment (aRR, 1.34; 95% CI, 1.29-1.40). When treated at private hospitals, 9-month isoniazid monotherapy was less likely to complete treatment, compared to 3-month isoniazid and rifampicin combination therapy (aRR, 1.33; 95% CI, 1.16-1.53).. Among employees of medical institutions with LTBI, only one third completed treatment. Age, occupation, treatment center, and initial regimen were significantly related to LTBI treatment performance indicators. Rifampicin-based short treatment regimens were effective under standard of care.

Topics: Adult; Antitubercular Agents; Cohort Studies; Health Personnel; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Physiologically based pharmacokinetic (PBPK) models have gained in popularity in the last decade in both drug development and regulatory science. PBPK models differ from classical pharmacokinetic models in that they include specific compartments for tissues involved in exposure, toxicity, biotransformation, and clearance processes connected by blood flow. This study aimed to address the gaps between the mathematics and pharmacology framework observed in the literature. These gaps included nonconserved systems of equations and compartment concentration that were not biologically relatable to the tissues of interest. The resulting system of nonlinear differential equations is solved numerically with various methods for benchmarking and comparison. Furthermore, a sensitivity analysis of all parameters were conducted to elucidate the critical parameters of the model. The resulting model was fit to clinical data as a performance benchmark. The clinical data captured the second line of antiretroviral treatment, lopinavir and ritonavir. The model and clinical data correlate well for coadministration of lopinavir/ritonavir with rifampin. Drug-drug interaction was captured between lopinavir and rifampin. This article provides conclusions about the suitability of physiologically based pharmacokinetic models for the prediction of drug-drug interaction and antiretroviral and anti-TB pharmacokinetics.

Topics: Anti-Retroviral Agents; HIV; HIV Infections; Humans; Latent Tuberculosis; Lopinavir; Models, Biological; Rifampin; Ritonavir; Tuberculosis

A once-weekly oral dose of isoniazid and rifapentine for 3 months (3HP) is recommended by the CDC for treatment of latent tuberculosis infection (LTBI). The aim of this study is to assess 3HP-mediated clearance of M. tuberculosis bacteria in macaques with asymptomatic LTBI. Twelve Indian-origin rhesus macaques were infected with a low dose (~10 CFU) of M. tuberculosis CDC1551 via aerosol. Six animals were treated with 3HP and 6 were left untreated. The animals were imaged via PET/CT at frequent intervals. Upon treatment completion, all animals except 1 were coinfected with SIV to assess reactivation of LTBI to active tuberculosis (ATB). Four of 6 treated macaques showed no evidence of persistent bacilli or extrapulmonary spread until the study end point. PET/CT demonstrated the presence of significantly more granulomas in untreated animals relative to the treated group. The untreated animals harbored persistent bacilli and demonstrated tuberculosis (TB) reactivation following SIV coinfection, while none of the treated animals reactivated to ATB. 3HP treatment effectively reduced persistent infection with M. tuberculosis and prevented reactivation of TB in latently infected macaques.

Topics: Animals; Antitubercular Agents; Isoniazid; Latent Tuberculosis; Lung; Macaca mulatta; Mycobacterium tuberculosis; Positron Emission Tomography Computed Tomography; Rifampin; Tuberculosis

Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.

Topics: Antitubercular Agents; Ethambutol; Humans; Isoniazid; Latent Tuberculosis; Pyrazinamide; Rifampin; Tuberculin; Tuberculosis; United States

Topics: Algorithms; Humans; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; Rural Population; Sensitivity and Specificity; Tuberculosis

One fourth of the global population has been infected with

Topics: Antitubercular Agents; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Topics: Animals; Antitubercular Agents; Drug Therapy, Combination; Isoniazid; Latent Tuberculosis; Mice; Rifampin

Topics: Abattoirs; Anti-Inflammatory Agents; Antitubercular Agents; Clofazimine; Dapsone; Diagnosis, Differential; Humans; Isoniazid; Latent Tuberculosis; Leprostatic Agents; Leprosy, Borderline; Leprosy, Multibacillary; Male; Middle Aged; Prednisolone; Rifampin; Thrombophlebitis

Short-course preventive therapy with 1-month course of daily administration of isoniazid (300-mg) plus rifapentine (600-mg) (1HP) and 3-month course of weekly administration of isoniazid (900-mg) plus rifapentine (900-mg) (3HP) has higher completion rates than 9-month course of daily isoniazid (9H) for individuals with latent tuberculosis infection (LTBI). We aimed to evaluate the effect, safety and tolerability of 1HP in people living with HIV (PLWH) and LTBI who received coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).. PLWH testing positive by interferon-gamma release assay and having received BIC/FTC/TAF for >2 weeks with plasma HIV RNA load (PVL) <200 copies/ml were enrolled. BIC trough plasma concentrations and cytokine profiles were determined before the first dose (day 1/baseline), 24 h after the 14th (day 15) and 28th (day 29) doses of 1HP. PVL were determined on days 15 and 29 of 1HP and every 3 months subsequently after discontinuation of 1HP.. BIC/FTC/TAF in combination with 1HP was well tolerated with a high completion rate. BIC trough plasma concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI. While transient viral blips were observed during 1HP without causing subsequent treatment failure, such combination should be applied with caution.

Topics: Adenine; Alanine; Amides; Anti-HIV Agents; Emtricitabine; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Piperazines; Pyridones; Rifampin; Tenofovir

Tuberculosis (TB) remains an important problem among children in the United States and throughout the world. There is no diagnostic reference standard for latent tuberculosis infection (also referred to as tuberculosis infection [TBI]). The tuberculin skin test (TST) has many limitations, including difficulty in administration and interpretation, the need for a return visit by the patient, and false-positive results caused by cross-reaction with Mycobacterium bovis-bacille Calmette-Guerin vaccines and many nontuberculous mycobacteria. Interferon-gamma release assays (IGRAs) are blood tests that use antigens specific for M tuberculosis; as a result, IGRAs yield fewer false-positive results than the TST. Both IGRAs and the TST have reduced sensitivity in immunocompromised children, including children with severe TB disease. Both methods have high positive predictive value when applied to children with risk factors for TBI, especially recent contact with a person who has TB disease. The advantages of using IGRAs and diminished experience with the placement and interpretation of the TST favor expanded use of IGRAs in children in the United States. There are now several effective and safe regimens for the treatment of TBI in children. For improved adherence to therapy, the 3 rifamycin-based regimens are preferred because of their short duration. Daily isoniazid can be used if there is intolerance or drug interactions with rifamycins. A TB specialist should be involved when there are questions regarding testing interpretation, selection of an appropriate treatment regimen, or management of adverse effects.

Topics: Adolescent; Age Factors; Antitubercular Agents; BCG Vaccine; Child; Child, Preschool; Cross Reactions; False Positive Reactions; Humans; Immunocompromised Host; Infant; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Mycobacterium bovis; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Rifampin; Sensitivity and Specificity; Tuberculin Test

HIV-1 mediated dysregulation of the immune response to tuberculosis and its effect on the response to antitubercular therapy (ATT) is incompletely understood. We aimed to analyse the inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection undergoing ATT, with specific focus on the effect of ART and HIV-1 viraemia in those co-infected with HIV-1.. In this prospective cohort study and immunological network analysis, a panel of 38 inflammatory markers were measured in the plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B clinic, Cape Town, South Africa. We recruited patients with sputum Xpert MTB/RIF-positive rifampicin-susceptible pulmonary tuberculosis. Patients were excluded from the primary discovery cohort if they were younger than 18 years, unable to commence ATT for any reason, pregnant, had unknown HIV-1 status, were unable to consent to study participation, were unable to provide baseline sputum samples, had more than three doses of ATT, or were being re-treated for tuberculosis within 6 months of their previous ATT regimen. Plasma samples were collected at baseline (1-5 days after commencing ATT), week 8, and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. In addition to the discovery cohort, a validation cohort of patients with HIV-1 admitted to hospital with CD4 counts less than 350 cells per μL and a high clinical suspicion of new tuberculosis were recruited.. Between March 1, 2013, and July 31, 2014, we assessed a cohort of 129 participants (55 [43%] female and 74 [57%] male, median age 35·1 years [IQR 30·1-43·7]) and 76 were co-infected with HIV-1. HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and having a strong effect on correlation profiles observed in the HIV-1 co-infected group. Interleukin (IL)-17A emerged as a key correlate of HIV-1-induced inflammation during HIV-tuberculosis co-infection.. Our findings show the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in patients with tuberculosis. Through network analysis we identified IL-17A as an important node in HIV-tuberculosis co-infection, thus implicating this cytokine's capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are required to identify specific IL-17A-related inflammatory pathways mediating immunopathology in HIV-tuberculosis co-infection, which could illuminate targets for future host-directed therapies.. National Institutes of Health, The Wellcome Trust, UK Research and Innovation, Cancer Research UK, European and Developing Countries Clinical Trials Partnership, and South African Medical Research Council.

Topics: Adult; Antitubercular Agents; Biomarkers; Cohort Studies; Coinfection; Female; HIV Infections; HIV Seropositivity; HIV-1; Humans; Interleukin-17; Latent Tuberculosis; Male; Prospective Studies; Rifampin; South Africa; Tuberculosis

Topics: Antibiotics, Antitubercular; Antitubercular Agents; Child; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program.. Retrospective cohort study.. The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort.. Systematic LTBI screening and therapy.. Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes.. Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ. 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy.. Retrospective data and generalizability outside low-TB-burden settings.. Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Topics: Aged; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Cohort Studies; Exanthema; Female; Gastrointestinal Diseases; Humans; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Male; Mass Screening; Middle Aged; Pruritus; Renal Dialysis; Retrospective Studies; Rifabutin; Rifampin; Treatment Outcome; Vitamin B 6

Treatment of latent tuberculosis (LTBI) is important for tuberculosis (TB) prevention, and short course rifamycin-based therapies are preferred. Once-weekly isoniazid-rifapentine by self-administered therapy (3HP-SAT) has never been compared with 4 months of daily rifampin (4R).. Retrospective cohort study of adults ≥18 years of age initiating LTBI treatment with either 3HP-SAT or 4R in a United States (US)-based TB clinic between 11 April 2016 and 31 December 2018. We evaluated treatment completion through pharmacy fills and reviewed charts for reasons of noncompletion, including adverse events (AEs). The χ 2 test and a log-binomial multivariable model were used to compare treatment completion and AEs.. Five hundred sixty individuals (42%) initiated 3HP-SAT and 773 (58%) initiated 4R. Median age was 38, 55% were female, and 89% were born outside of the US. Among those aged 18-49 years, treatment completion with 3HP-SAT was 79% compared to 68% with 4R (adjusted risk ratio [aRR], 1.17 [95% CI, 1.17-1.27]; P < .0001). Among individuals aged ≥50 years, treatment completion with 3HP-SAT was 87% compared to 64% with 4R (aRR, 1.35 [95% CI, 1.19-1.52]; P < .0001). Compared to 4R, there was no difference in risk of AEs in the 18-49 age group (aRR, 0.93 [95% CI, .58-1.48]; P = .75). Reduced risk of AEs was noted among patients aged ≥50 years who received 3HP-SAT (aRR, 0.37 [95% CI, .16-.85]; P = .02).. 3HP-SAT was associated with higher LTBI treatment completion and lower rates of AEs compared to 4R in individuals aged 50 and older. Expanding 3HP-SAT as an option for patients with LTBI may enhance TB prevention strategies in the US.

Topics: Adult; Aged; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Retrospective Studies; Rifampin; United States

Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR-DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.

Topics: Antitubercular Agents; Humans; Latent Tuberculosis; Metformin; Microbial Sensitivity Tests; Molecular Docking Simulation; Mycobacterium tuberculosis; Rifampin

Weekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential.. Participants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation.. Overall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs.. With proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively. Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.

Topics: Aged; Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Rifampin

The lengthy TB chemotherapeutic regimen, resulting in the emergence of drug resistance strains, poses a serious problem in the cure of the disease. Further, one-quarter of the world's population is infected with dormant M.tb, which creates a lifetime risk of reactivation. M.tb has a remarkable tendency to escape the host immune responses by hiding in unconventional niches. Recent studies have shown that bone-marrow mesenchymal stem cells (BM-MSCs) can serve as a reservoir of the pathogen and have been suggested to keep them beyond the reach of anti-TB drugs. In this study, we have shown that M.tb infects and grows inside BM-MSCs and were unresponsive to the anti-TB drugs rifampicin and isoniazid when compared to the pathogen residing inside THP-1 macrophages. It was further shown that the ABCG2 efflux pumps of the BM-MSCs were upregulated upon exposure to rifampicin, which may be the contributing factor for the antibiotic unresponsiveness of the bacteria inside these cells. Subsequently, it was shown that inhibition of ABCG2 efflux pumps along with administration of anti-TB drugs led to an increased susceptibility and consequently an enhanced killing of the M.tb inside BM-MSCs. These findings for the first time show that the MIC

Topics: Antitubercular Agents; ATP Binding Cassette Transporter, Subfamily G, Member 2; Drug Resistance, Bacterial; Humans; Isoniazid; Latent Tuberculosis; Macrophages; Mesenchymal Stem Cells; Mycobacterium tuberculosis; Rifampin

Successful delivery and completion of tuberculosis preventive treatment are necessary for tuberculosis elimination. Shorter preventive treatment regimens currently have higher medication costs, but patients spend less time in care and are more likely to complete treatment. It is unknown how economic costs of successful delivery differ between longer and shorter regimens in high-tuberculosis-burden settings.. We developed survey instruments to collect costs from program and patient sources, considering costs incurred from when household contacts first entered the health system. We compared the cost per completed course of preventive treatment with either 6 months of daily isoniazid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network tuberculosis program in Karachi, Pakistan, between October 2016 and February 2018.. During this period, 459 individuals initiated 6H and 643 initiated 3HP; 39% and 61% completed treatment, respectively. Considering costs to both the program and care recipients, the cost per completed course was 394 US dollars (USD) for 6H and 333 USD for 3HP. Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP to 290 USD. Under varying assumptions about drug prices and costs incurred by care recipients, the cost per completed course was lower for 3HP in all scenarios, and the largest cost drivers were the salaries of clinical staff.. In a high-burden setting, the cost of successful delivery of 3HP was lower than that of 6H, driven by higher completion.

Topics: Antitubercular Agents; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Tuberculosis

A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of active tuberculosis (TB); however, it is unclear whether 3HP should be provided by directly observed therapy (DOT) or self-administered therapy (SAT). In addition, the introduction of patient informed choice between delivery modalities may have a positive impact on factors leading to treatment completion. The authors randomized 252 participants with HIV to a hypothetical scenario of providing preventive therapy by either DOT or an informed choice between DOT and SAT. Out of 104 participants who were randomized to a choice between DOT and SAT, 103 chose therapy by SAT. Participants rated their level of confidence and intention to complete therapy. Compared to those assigned to the DOT scenario, patients assigned to the choice scenario expressed greater confidence and intention to complete preventive therapy. Convenience and travel required to complete 3HP therapy were important factors in deciding between delivery modalities. Those assigned to DOT identified more barriers to completing therapy than those given a choice. Empowering patients to make informed decisions about how they receive TB preventive therapy may improve completion rates.

Topics: Adult; Decision Making; Directly Observed Therapy; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Patient Preference; Random Allocation; Rifampin; Self Administration; Self Efficacy; Uganda

Objective　This study aimed to evaluate the treatment outcome of latent tuberculosis infection (LTBI) in persons with fibrotic pulmonary lesions, treated with isoniazid (INH) or rifampicin (RFP) in Nishinari Ward, Osaka City.Methods　As part of a tuberculosis screening program by chest X-ray (CXR), we selected persons who met the following four criteria for initiation of LTBI treatment:①Anti-tuberculosis treatment has not been performed for more than one month in the past. ②CXR shows fibrotic pulmonary lesions.③Fibrotic pulmonary lesions with CXR have not changed for more than one year.④QuantiFERON TB Gold-in-tube (QFT) shows positive values (≥0.35 IU/mL).　Before treatment, the blood samples were within the standard values for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and serum creatinine. Treatment with INH was stopped when AST or ALT levels were elevated to more than 150 IU/L, or symptoms of liver dysfunction appeared even when AST or ALT levels were less than 150 IU/L. After liver dysfunction improved, treatment with RFP was started.　Treatment completion was defined as being dispensed with INH for ≥180 days or RFP for ≥120 days.Results　The 27 participants were all male and their age was 68.4±6.6 years. Of the 27 participants, 14 (51.9%) completed treatment with INH. Of the remaining 13 persons, nine (69.2%) stopped treatment with INH because of liver dysfunction. Nine restarted RFP treatment and all participants completed the treatment without interruption by liver dysfunction. In total, 23 (85.2%) completed the treatment.Conclusion　LTBI treatment with INH in persons with fibrotic pulmonary lesions in the area where people in financial need live was stopped because of liver dysfunction; however, changes from INH to RFP could improve treatment outcomes.

Topics: Aged; Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin; Treatment Outcome

Topics: Adult; Antibiotics, Antitubercular; Antibodies, Monoclonal; Female; Humans; Injections, Subcutaneous; Latent Tuberculosis; Pityriasis Rubra Pilaris; Rifampin

To assess the cost effectiveness of once weekly rifapentine and isoniazid for 12 weeks (3HP) to the current standard care for latent tuberculosis (TB) infection (LTBI) in Iqaluit, Nunavut.. A cost-effectiveness analysis using a Markov model reflecting local practices for LTBI treatment.. A remote Canadian arctic community with a high incidence of TB.. Hypothetical patients with LTBI.. The cost effectiveness of 3HP was compared with the existing standard of care in the study region which consists of 9 months of twice weekly isoniazid (9H) given by directly observed therapy.. Effectiveness was measured in quality-adjusted life years (QALYs) with model parameters were derived from historical programmatic data, a local implementation study of 3HP and published literature. Costs from the perspective of the Nunavut healthcare system were measured in 2019 US dollars and were obtained primarily from local, empirically collected data. Secondary health outcomes included estimated TB cases and TB deaths averted using 3HP versus 9H. One way and probabilistic sensitivity analyses were performed.. The 3HP regimen was dominant over 9H: costs were lower (US$628 vs US$924/person) and health outcomes slightly improved (20.14 vs 20.13 QALYs/person). In comparison to 9H, 3HP treatment resulted in fewer TB cases (27.89 vs 30.16/1000 persons) and TB deaths (2.29 vs 2.48/1000 persons). 3HP completion, initiation and risk of fatal adverse events were the primary drivers of cost effectiveness.. In a remote Canadian arctic setting, using 3HP instead of 9H for LTBI treatment may result in cost savings and similar or improved health outcomes.

Topics: Antitubercular Agents; Canada; Cost-Benefit Analysis; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Three months of weekly rifapentine plus isoniazid (3HP) is a short course regimen for latent tuberculosis infection treatment with satisfied safety and efficacy. However, research on its use in children is limited. In this study, we evaluated the completion rate and safety of the 3HP regimen among children in China. Participants aged 1-14 years receiving 3HP for TB prevention at Shanghai Public Health Clinical Center were followed from December 2019 to November 2020 to evaluate the safety and completion rate of the treatment. Thirty-one children were eligible for inclusion, but five were excluded from the analysis (three were treated with a lower than recommended dose, and two were lost to follow-up). Of the 26 children included in the analysis, the treatment completion rate was 100%. Adverse drug reactions (ADRs) were reported in 38.5% (10/26) of the patients. The most common ADRs were gastrointestinal symptoms (19.2%,5/26), and all ADRs were rated as Grade 1. The 3HP regimen has a high completion rate, and it seems well tolerated in our study population. However, further randomized controlled clinical trial with larger sample size are warranted.

Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; China; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Rifampin

HIV-1 mediated dysregulation of the immune response to tuberculosis and its effect on the response to antitubercular therapy (ATT) is incompletely understood. We aimed to analyse the inflammatory profile of patients with tuberculosis with or without HIV-1 co-infection undergoing ATT, with specific focus on the effect of ART and HIV-1 viraemia in those co-infected with HIV-1.. In this prospective cohort study and immunological network analysis, a panel of 38 inflammatory markers were measured in the plasma of a prospective patient cohort undergoing ATT at Khayelitsha Site B clinic, Cape Town, South Africa. We recruited patients with sputum Xpert MTB/RIF-positive rifampicin-susceptible pulmonary tuberculosis. Patients were excluded from the primary discovery cohort if they were younger than 18 years, unable to commence ATT for any reason, pregnant, had unknown HIV-1 status, were unable to consent to study participation, were unable to provide baseline sputum samples, had more than three doses of ATT, or were being re-treated for tuberculosis within 6 months of their previous ATT regimen. Plasma samples were collected at baseline (1-5 days after commencing ATT), week 8, and week 20 of ATT. We applied network and multivariate analysis to investigate the dynamic inflammatory profile of these patients in relation to ATT and by HIV status. In addition to the discovery cohort, a validation cohort of patients with HIV-1 admitted to hospital with CD4 counts less than 350 cells per μL and a high clinical suspicion of new tuberculosis were recruited.. Between March 1, 2013, and July 31, 2014, we assessed a cohort of 129 participants (55 [43%] female and 74 [57%] male, median age 35·1 years [IQR 30·1-43·7]) and 76 were co-infected with HIV-1. HIV-1 status markedly influenced the inflammatory profile regardless of ATT duration. HIV-1 viral load emerged as a major factor driving differential inflammatory marker expression and having a strong effect on correlation profiles observed in the HIV-1 co-infected group. Interleukin (IL)-17A emerged as a key correlate of HIV-1-induced inflammation during HIV-tuberculosis co-infection.. Our findings show the effect of HIV-1 co-infection on the complexity of plasma inflammatory profiles in patients with tuberculosis. Through network analysis we identified IL-17A as an important node in HIV-tuberculosis co-infection, thus implicating this cytokine's capacity to correlate with, and regulate, other inflammatory markers. Further mechanistic studies are required to identify specific IL-17A-related inflammatory pathways mediating immunopathology in HIV-tuberculosis co-infection, which could illuminate targets for future host-directed therapies.. National Institutes of Health, The Wellcome Trust, UK Research and Innovation, Cancer Research UK, European and Developing Countries Clinical Trials Partnership, and South African Medical Research Council.

Topics: Adult; Antitubercular Agents; Biomarkers; Cohort Studies; Coinfection; Female; HIV Infections; HIV Seropositivity; HIV-1; Humans; Interleukin-17; Latent Tuberculosis; Male; Prospective Studies; Rifampin; South Africa; Tuberculosis; United States

Topics: Animals; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Isoniazid; Latent Tuberculosis; Macaca; Models, Animal; Mycobacterium tuberculosis; Rifampin; Treatment Outcome; Tuberculosis

Efficient recruitment of eligible participants, optimizing time and sample size, is a crucial component in conducting a successful clinical trial. Inefficient participant recruitment can impede study progress, consume staff time and resources, and limit quality and generalizability or the power to assess outcomes. Recruitment for disease prevention trials poses additional challenges because patients are asymptomatic. We evaluated candidates for a disease prevention trial to determine reasons for nonparticipation and to identify factors that can be addressed to improve recruitment efficiency.. During 2001-2009, the Tuberculosis Trials Consortium conducted Study 26 (PREVENT TB), a randomized clinical trial at 26 sites in four countries, among persons with latent tuberculosis infection at high risk for tuberculosis disease progression, comparing 3 months of directly observed once-weekly rifapentine plus isoniazid with 9 months of self-administered daily isoniazid. During March 2005-February 2008, non-identifying demographic information, risk factors for experiencing active tuberculosis disease, and reasons for not enrolling were collected from screened patients to facilitate interpretation of trial data, to meet Consolidated Standards of Reporting Trials standards, and to evaluate reasons for nonparticipation.. Of the 7452 candidates screened in Brazil, Canada, Spain, and the United States, 3584 (48%) were not enrolled, because of ineligibility (41%), site decision (10%), or patient choice (49%). Among those who did not enroll by own choice, and for whom responses were recorded on whether they would accept treatment outside of the study (n = 1430), 68% reported that they planned to accept non-study latent tuberculosis infection treatment. Among 1305 patients with one or more reported reasons for nonparticipation, study staff recorded a total of 1886 individual reasons (reason count: median = 1/patient; range = 1-9) for why patients chose not to enroll, including grouped concerns about research (24% of 1886), work or school conflicts (20%), medication or health beliefs (16%), latent tuberculosis infection beliefs (11%), and patient lifestyle and family concerns (10%).. Educational efforts addressing clinical research concerns and beliefs about medication and health, as well as study protocols that accommodate patient-related concerns (e.g. work, school, and lifestyle) might increase willingness to enter clinical trials. Findings from this evaluation can support development of communication and education materials for clinical trial sites at the beginning of a trial to allow study staff to address potential participant concerns during study screening.

Topics: Adolescent; Adult; Antitubercular Agents; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Patient Selection; Randomized Controlled Trials as Topic; Refusal to Participate; Rifampin; Risk Factors; Young Adult

Topics: Animals; Isoniazid; Latent Tuberculosis; Macaca; Mycobacterium tuberculosis; Rifampin

Although rare, subclinical tuberculosis disease can be missed during evaluations for latent tuberculosis infection, and can manifest with symptoms during latent tuberculosis treatment. Among over 8000 patients treated for latent tuberculosis we found no evidence of acquired drug resistance, underscoring the safety of rifampin monotherapy for latent tuberculosis.

Topics: Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Tuberculosis

An important problem limiting treatment of latent tuberculosis infection is the occurrence of adverse events with isoniazid. We combined populations from phase 2 and phase 3 open-label, randomised controlled trials, to establish risk factors for adverse events during latent tuberculosis infection treatment.. We did a post-hoc safety analysis based on data from two open-label, randomised controlled trials done in health-care facilities in Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea. Participants were consenting adults (aged ≥18 years) with a positive latent tuberculosis infection diagnostic test, indication for treatment, and without contraindications to rifampicin or isoniazid. Patients were centrally randomly assigned 1:1 to 4 months of daily 10 mg/kg rifampicin or 9 months of daily 5 mg/kg isoniazid. The primary outcome evaluated was adverse events (including grade 1-2 rash and all events of grade 3-5) resulting in permanent discontinuation of study medication and judged possibly or probably related to study drug by a masked, independent, three-member adjudication panel (trial registration: NCT00170209; NCT00931736).. Participants were recruited from April 27, 2004, up until Jan 31, 2007 (phase 2), and Oct 1, 2009, up until Dec 31, 2014 (phase 3). The safety populations for each group comprised 3205 individuals receiving isoniazid and 3280 receiving rifampicin. Among those receiving isoniazid, 86 (2·7%) of 3205 had grade 1-2 rash or any grade 3-5 adverse events, more than the 50 (1·5%) of 3280 who had these events with rifampicin (risk difference -1·2%, 95% CI -1·9 to -0·5). Age was associated with adverse events in adults receiving isoniazid. Compared with individuals aged 18-34 years, the adjusted odds ratio (OR) for adverse events was 1·8 (95% CI 1·1-3·0) for individuals aged 35-64 years and 3·0 (1·2-6·8) for individuals aged 65-90 years. With rifampicin, adverse events were associated with inconsistent medication adherence (adjusted OR 2·0, 1·1-3·6) and concomitant medication use (2·8, 1·5-5·2), but not age, with an adjusted OR of 1·1 (0·6-2·1) for individuals aged 35-64 years and 1·7 (0·5-4·7) for individuals aged 65-90 years. One treatment-related death occurred in the isoniazid group.. In patients without a contraindication, rifampicin is likely to be the safest latent tuberculosis infection treatment option. With more widespread use of rifampicin, rare, but serious adverse events might be seen. However, within these randomised trials, rifampicin was safer than isoniazid and adverse events were not associated with older age. Therefore, rifampicin should become a primary treatment option for latent tuberculosis infection based on its safety.. Canadian Institutes of Health Research.

Topics: Adult; Africa; Americas; Antitubercular Agents; Asia; Australia; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifampin; Risk Factors

Topics: Adult; Antitubercular Agents; Drug Administration Schedule; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Treatment data for latent tuberculosis infection (LTBI) among potential living kidney donors are scarce.. This retrospective study was performed to evaluate the prevalence of positive QuantiFERON-TB Gold In-Tube (QFT-GIT) among potential living kidney donors that were screened from 2009 to 2017. We investigated if there was any difference in the time to donation between QFT-GIT-positive and QFT-GIT-negative donors. We assessed the regimens used to treat LTBI and whether the recipients of QFT-GIT-positive donors developed active tuberculosis (TB).. Forty out of 427 (9%) potential living kidney donors had a positive QFT-GIT. QFT-GIT-positive donors were as likely as negative donors to undergo donation (30 [75%] vs 315 [81%], P = .33). The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors (median 221 days [range: 4-1139] vs 86 days [range: 3-1887], P = .001). Twelve-week rifapentine (RPT)/Isoniazid (INH) was the most common treatment used and was not associated with significant adverse reactions. There was a trend toward longer time to donation among QFT-GIT-positive donors who were treated for LTBI compared with QFT-GIT-positive donors who were not (252 days [range: 88-1139] vs 95 days [range: 4-802], P = .05). Twenty-nine recipients of QFT-GIT-positive living kidney donors were evaluated. Eleven of these recipients received kidneys from donors that were not treated for LTBI. Two of these recipients were treated with INH post-transplantation.. The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors. The short-course regimens appear to be excellent options for LTBI treatment among living kidney donors and avoid delaying organ donation further.

Topics: Adult; Antibiotics, Antitubercular; Drug Administration Schedule; Humans; Interferon-gamma Release Tests; Kidney; Kidney Transplantation; Latent Tuberculosis; Living Donors; Male; Middle Aged; Mycobacterium tuberculosis; Prevalence; Retrospective Studies; Rifampin

Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R)

Topics: Antitubercular Agents; Canada; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Humans; Isoniazid; Latent Tuberculosis; Quebec; Retrospective Studies; Rifampin

We present a case of a young Asian female with rheumatoid arthritis who received latent tuberculosis infection (LTBI) treatment prior to treatment with a biologic agent, and developed shock with resistant hypotension on re-exposure to rifampicin. We discuss the epidemiology, pathophysiology and management of rifampicin induced shock, concluding that clinicians should be aware of this rare, but potential adverse effect, and be aware that adverse reactions to rifampicin are more frequent during re-exposure or longer dosing interval regimes. The evidence for desensitisation following such a reaction is lacking and this approach is not currently recommended. We would suggest close collaboration between specialties prescribing immunosuppression and the tuberculosis team when LTBI treatment is required after a reaction, with patient involvement to discuss the risks and benefits of treatment options.

Topics: Adult; Antitubercular Agents; Female; Fluid Therapy; Humans; Hypotension; Latent Tuberculosis; Retreatment; Rifampin; Shock, Septic

The objective of this study was to evaluate a novel collaborative care model using community pharmacies as additional access points for latent tuberculosis infection (LTBI) treatment for patients using combination weekly therapy with isoniazid and rifapentine (3HP) plus directly observed therapy for 12 weeks.. This prospective pilot study included adult patients diagnosed with LTBI. Patients were eligible for study participation if they spoke English or Spanish and were followed by the New Mexico Department of Health (NM DOH). Patients were excluded if they were pregnant, receiving concomitant HIV antiretroviral therapy, or had contraindications to 3HP due to allergy or drug interactions. Community pharmacy sites included chain, independent, and hospital outpatient pharmacies in Albuquerque and Santa Fe, New Mexico.. A total of 40 patients initiated treatment with 3HP and were included. Most were female (55%) and had a mean age of 46 years (standard deviation, 12.6 y). A total of 75.0% of patients completed LTBI treatment with 3HP in a community pharmacy site. Individuals of Hispanic ethnicity were more likely to complete treatment (76.7% vs 40.0%, P = .04). Most patients (60%; n = 24) reported experiencing an adverse drug event (ADE) with 3HP therapy. Patients who completed treatment were less likely to experience an ADE than patients who discontinued treatment (50.0% vs 90.0%, P = .03). Pharmacists performed 398 LTBI treatment visits (40 initial visits, 358 follow-up visits), saving the NM DOH approximately 143 hours in patient contact time.. High completion rates and safe administration of LTBI treatment can be achieved in the community pharmacy setting.

Topics: Adult; Antibiotics, Antitubercular; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; New Mexico; Pharmacies; Pilot Projects; Prospective Studies; Public Health; Rifampin

Screening for latent tuberculosis infection (LTBI) is indicated before immunosuppressive therapies but is complicated by lack of a gold standard and limited by, e.g., immunosuppression. This study aimed to investigate a series of patients diagnosed with LTBI during screening before immunosuppressive therapy, describing how the use of diagnostic tests and treatment evolved over time. This retrospective cohort study included all individuals diagnosed with LTBI during screening before intended immunosuppressive therapy in a tertiary care hospital between January 2000 and December 2017. Evidence for LTBI, including history, tuberculin skin test (TST), QuantiFERON (QFT) result and suggestive lesions on chest radiography (CXR), and CT scan if available, was analyzed. The study included 295 individuals with LTBI, with median follow-up of 3.8 years (IQR 1.7-7.4 years). During screening, TST, QFT, and CXR were positive in 80.8%, 53.4%, and 22.7%, respectively. Chest CT revealed lesions associated with past tuberculosis infection in around 70%, significantly more frequent than CXR. In patients diagnosed with LTBI, we observed that the use of TST declined over time whereas the use of QFT increased, and that isoniazid was replaced with rifampicin as preferential treatment. Preventive treatment was started in 82.3%, of whom 88.6% completed treatment. During follow-up, no individuals developed active tuberculosis. The diagnosis of LTBI was based on history, TST, QFT, and/or CXR in nearly every possible combination, but mostly on TST and QFT. The most striking trends were the decreased use of TST, increased use of QFT, and the replacement of isoniazid with rifampicin for treatment.

Topics: Adult; Aged; Antitubercular Agents; Female; Follow-Up Studies; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Radiography, Thoracic; Retrospective Studies; Rifampin; Tertiary Care Centers; Tuberculin Test

China is one of the countries with a high burden of tuberculosis (TB) and latent tuberculosis infection (LTBI). It was recently estimated that China had the highest LTBI burden in the world, with approximately 350 million persons living with the infection. The prevalence of LTBI in China is overestimated by tuberculin skin test (TST) as compared to interferon-gamma release assay (IGRA). A population-based study found that IGRA positivity rates ranged between 13.5% and 19.8%. The annual TB infection rate in the rural population was 1.5% based on persistent positive IGRA results in converters. The development of active TB from LTBI in the general rural population was 0.87 per 100 person-years in the first 2 years among individuals who newly converted to IGRA-positive. TB control in students has been paid more attention by the government, which also improved LTBI management among students in close contact with active TB patients. A 3-month regimen of twice-weekly rifapentine plus isoniazid (3H

Topics: Antitubercular Agents; China; Humans; Incidence; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Prevalence; Rifampin; Rural Population; Tuberculin Test; Tumor Necrosis Factor-alpha

To estimate the cost of a screening program for identifying latent tuberculosis (TB) infections in migrants to Oman.. A Markov model was used to estimate the cost of screening using an interferon-gamma release assay (IGRA) applied to all migrants from high TB endemic countries, followed by preventive TB treatment.. The model compared seven different scenarios, with a comparison of the direct cost and the quality-adjusted life-years (QALYs) saved.. IGRA testing followed by 3 months of preventive treatment with rifapentine/isoniazid (3HP) was the most cost-effective intervention.

Topics: Cost-Benefit Analysis; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Markov Chains; Mass Screening; Oman; Quality-Adjusted Life Years; Rifampin; Transients and Migrants; Tuberculosis

We analyzed data from 2012 to 2016 for patients who were hospitalized or who died after ≥1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension, and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment.

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; United States

Topics: Adult; Antibiotics, Antitubercular; Child; Clinical Trials as Topic; Drug Therapy, Combination; Guidelines as Topic; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Mass Screening; Mycobacterium tuberculosis; Rifampin; Time Factors

Rifampin is known to influence the pharmacokinetics of tofacitinib owing to drug interactions. The aim of this study was to determine the efficacy of tofacitinib on co-administration with rifampin in rheumatoid arthritis (RA) patients.. Biologic-naïve RA patients treated with tofacitinib were selected, and electronic medical reports were reviewed retrospectively. All patients underwent screening for latent tuberculosis infection (LTBI) before starting tofacitinib, and patients with positive results were treated to prevent progression to active tuberculosis. To evaluate the efficacy of tofacitinib with or without rifampin, the discontinuation rates of tofacitinib were examined during the first 6 months. Kaplan-Meier analysis was used to construct cumulative discontinuation curves, and comparisons were performed using the log-rank test.. Among 81 patients who starting tofacitinib, 21 were LTBI-positive and 18 were administered rifampin concomitantly with tofacitinib. Additionally, 14 of the 81 patients (17.3%) discontinued tofacitinib during the follow-up, and 7 patients discontinued tofacitinib because of uncontrolled RA activity. The discontinuation rates of tofacitinib within the first 6 months were significantly higher in patients treated with rifampin for LTBI than in those not treated with rifampin (lack of efficacy: 24.7% vs. 5.1%, P<0.01; all causes: 38.9% vs. 11.2%, P<0.01).. Discontinuation rates were higher in RA patients who started tofacitinib during chemoprophylaxis involving rifampin than in those who did not receive rifampin. Physicians should be aware that the efficacy of tofacitinib could be decreased by chemoprophylactic regimens for tuberculosis.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Latent Tuberculosis; Piperidines; Pyrimidines; Retrospective Studies; Rifampin; Treatment Outcome

The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited.. This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (<60 years old) were analyzed.. A total of 406 LTBI patients, comprising 167 elderly and 239 young patients, were included in the analyses. The incidence of SARs was similar in the elderly group (18%) and the young group (15.1%). Being middle-aged (35-59 years), body mass index <23 kg/m. The occurrence of SARs was similar in the elderly (≥60 years old) and young (<60 years old) LTBI patients receiving preventive therapy. Extremely old (≥80 years old) LTBI patients had a higher treatment interruption rate, especially when they had SARs.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Incidence; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Male; Middle Aged; Prospective Studies; Rifampin; Taiwan

Understanding the biology of the tuberculosis pathogen during dormant asymptomatic infection, called latent tuberculosis is crucial to decipher a resilient therapeutic strategy for the disease. Recent discoveries exhibiting presence of pathogen's DNA and bacilli in mesenchymal stem cells (MSCs) of human and mouse despite completion of antitubercular therapy, indicates that these specific cells could be one of the niches for dormant Mycobacterium tuberculosis in humans. To determine if in vitro infection of human MSCs could recapitulate the in vivo characteristics of dormant M. tuberculosis, we examined survival, phenotype, and drug susceptibility of the pathogen in MSCs. When a very low multiplicity of infection (1:1) was used, M. tuberculosis could survive in human bone marrow derived MSCs for more than 22 days without any growth. At this low level of infection, the pathogen did not cause any noticeable host cell death. During the later phase of infection, MSC-residing M. tuberculosis exhibited increased expression of HspX (a 16-kDa alpha-crystallin homolog) with a concurrent increase in tolerance to the frontline antitubercular drugs Rifampin and isoniazid. These results present a human MSC-based intracelllular model of M. tuberculosis infection to dissect the mechanisms through which the pathogen acquires and maintains dormancy in the host.

Topics: Animals; Anti-Infective Agents; Antigens, Bacterial; Antitubercular Agents; Bacterial Proteins; Bone Marrow; Cell Survival; Drug Tolerance; Host-Pathogen Interactions; Humans; Isoniazid; Latent Tuberculosis; Mesenchymal Stem Cells; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Phenotype; Rifampin; Tuberculosis

Topics: Humans; Isoniazid; Latent Tuberculosis; Rifampin

Objective Treating latent tuberculosis infection (LTBI) is essential for eliminating the serious endemicity of tuberculosis. A shorter regimen is preferred to longer regimens because the former has better adherence with a better safety profile. However, lengthy treatment with isoniazid is still recommended in Japan. Based on the latest evidence, we switched from a conventional nine-month isoniazid regimen to a shorter four-month rifampin regimen for the treatment of LTBI. Methods To evaluate the safety and efficacy of the shorter regimen, we conducted Bayesian analyses using a stochastic mathematical model to calculate the posterior probabilities of several parameters. Patients Clinical data of 13 patients in the isoniazid group and 5 in the rifampin group were used for the Bayesian analyses. The outcomes measured were completion of the treatment, adverse effects, number of clinic visits, and medical costs. Results The medial posterior probability of the isoniazid group completing the treatment was 66% [95% credible interval (CrI) 43-89%], whereas that of the rifampin group was 86% (95% CrI 60-100%). The probability that the completion rate in the rifampin group was better than that in the isoniazid group was as high as 88% (95% CrI 0-100%). Other parameters, such as the number of clinical visits and duration of treatment, were better with rifampin therapy than with isoniazid therapy, with comparable medical costs. Conclusion Four months of rifampin therapy might be preferred to isoniazid for treating LTBI in Japan.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Bayes Theorem; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoniazid; Japan; Latent Tuberculosis; Male; Markov Chains; Middle Aged; Monte Carlo Method; Rifampin

Topics: Bayes Theorem; Data Analysis; Humans; Isoniazid; Japan; Latent Tuberculosis; Markov Chains; Monte Carlo Method; Rifampin

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin; United States

Preventive therapy is essential for reducing tuberculosis (TB) burden among people living with HIV (PLWH) in high-burden settings. Short-course preventive therapy regimens, such as three-month weekly rifapentine and isoniazid (3HP) and one-month daily rifapentine and isoniazid (1HP), may help facilitate uptake of preventive therapy for latently infected patients, but the comparative cost-effectiveness of these regimens under different conditions is uncertain.. We used a Markov state-transition model to estimate the incremental costs and effectiveness of 1HP versus 3HP in a simulated cohort of patients attending an HIV clinic in Uganda, as an example of a low-income, high-burden setting in which TB preventive therapy might be prescribed to PLWH. Our primary outcome was the incremental cost-effectiveness ratio, expressed as 2019 US dollars per disability-adjusted life year (DALY) averted. We estimated cost-effectiveness under different conditions of treatment completion and efficacy of 1HP versus 3HP, latent TB prevalence and rifapentine price.. Assuming equivalent clinical outcomes using 1HP and 3HP and a rifapentine price of $0.21 per 150 mg, 1HP would cost an additional $4.66 per patient treated. Assuming equivalent efficacy but 20% higher completion with 1HP versus 3HP, 1HP would cost $1,221 per DALY averted relative to 3HP. This could be reduced to $18 per DALY averted if 1HP had 5% greater efficacy than 3HP and the price of rifapentine were 50% lower. At a rifapentine price of $0.06 per 150 mg, 1HP would become cost-neutral relative to 3HP.. 1HP has the potential to be cost-effective under many realistic circumstances. Cost-effectiveness depends on rifapentine price, relative completion and efficacy, prevalence of latent TB and local willingness-to-pay.

Topics: Anti-HIV Agents; Antitubercular Agents; Cost-Benefit Analysis; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; Humans; Isoniazid; Latent Tuberculosis; Male; Quality-Adjusted Life Years; Rifampin; Tuberculosis; Uganda

Topics: Aged; Antibodies, Monoclonal, Humanized; Antitubercular Agents; Contraindications, Drug; Dermatologic Agents; Female; Humans; Interleukin-17; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Psoriasis; Rifampin

There are insufficient data on the treatment of latent tuberculosis infection (LTBI) in elderly patients. We investigated the completion rate of treatment in elderly LTBI patients.. A retrospective multicentre study was conducted at five university hospitals in South Korea. We reviewed the electronic medical records of patients aged 65 years and older who were diagnosed with LTBI via positive interferon-gamma release assay results between January 2016 and December 2018. Treatment completion was defined as ingestion of more than 80% of all prescribed medications without loss to follow-up.. During the study period, 127 LTBI patients aged 65 years and older visited outpatient department. Among them, 77 patients aged 65-78 years (median age, 69 years [interquartile range, 66-71 years]) who received LTBI treatment were analysed. Common reasons for IGRA testing in elderly patients were health-care worker (n = 33, 42.9%) and household contact with infectious TB patients (n = 18, 23.4%). The overall completion rate of LTBI treatment was 83.1% (n = 64), and the completion rate of 3-month isoniazid plus rifampin regimen was 88.4%. Adverse effects were reported in 23 patients (29.9%), and an increase in aminotransferase level was the most common adverse effect (n = 11, 14.3%). Three patients (3.9%) with the adverse effect discontinued treatment and 10 (13.0%) patients were lost to follow-up.. LTBI treatment in patients aged 65-78 years was relatively well tolerated. In LTBI treatment in elderly patients, the majority of discontinuation of treatment was due to loss to follow-up rather than adverse effects of anti-TB medications.

Topics: Aged; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Lost to Follow-Up; Male; Republic of Korea; Retrospective Studies; Rifampin

Healthcare workers (HCWs) are one of the target groups for systematic testing and treatment of latent tuberculosis infection (LTBI) in a setting of low TB incidence. We performed this study to describe the testing of HCWs for LTBI and analyse the acceptance and completion of treatment of LTBI.. This retrospective cohort study was conducted in four university-affiliated hospitals between January 1 and December 31, 2018. HCWs with positive interferon-gamma release assay (IGRA) during LTBI screening were analysed. We assessed the acceptance and completion of LTBI treatment.. Overall, 893 HCWs were IGRA positive. Among them, 609 HCWs visited the clinic for evaluation of LTBI. Of 609 HCWs who were evaluated, 302 (49.6%) were offered treatment for LTBI. The proportion of acceptance for treatment was 64.5% (195 of 302 HCWs). The treatment course was completed by 143 of 195 HCWs (73.3%). Three months of isoniazid and rifampin (3HR) was used in 137 HCWs (70.3%) and 4 months of rifampin (4R) in 58 (29.7%). 72 HCWs (36.9%) experienced at least one adverse drug events, but there was no different characteristics between completer and non-completer.. The acceptance and completion of LTBI treatment were unsatisfactory. Subjective perspective regarding obstacles to treatment of LTBI needs to be explored to increase compliance to LTBI treatment.

Topics: Adult; Aged; Antitubercular Agents; Asian People; Female; Health Personnel; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Mass Screening; Medication Adherence; Middle Aged; Patient Acceptance of Health Care; Republic of Korea; Retrospective Studies; Rifampin; Young Adult

Topics: Canada; Humans; Latent Tuberculosis; Rifampin

Topics: Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Odds Ratio; Polymorphism, Single Nucleotide; Rifampin

The consequences of once-weekly rifapentine plus isoniazid for 3 months (3HP) against latent tuberculosis infections in hemodialysis patients have not been studied before. This is the first study to evaluate the safety and tolerability of 3HP in this population and revealed a completion rate of 65.4%. The therapy was not associated with hepatotoxicity, but with high rates of adverse events (69.2%).

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Male; Middle Aged; Renal Dialysis; Rifampin; Safety

Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen.. To evaluate the cost-effectiveness of all regimens for treating LTBI.. We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon.. Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained.. Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Cost-Benefit Analysis; Decision Support Techniques; Drug Therapy, Combination; Female; Health Care Costs; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin; Young Adult

Topics: Adolescent; Adult; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Retrospective Studies; Rifampin; Risk; Treatment Outcome; Young Adult

To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure.. The study included 213 consecutive, naïve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks.. Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure.. The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Ascariasis; Brucellosis; Doxycycline; Drug Therapy, Combination; Egypt; Female; Humans; Latent Tuberculosis; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies; Rifampin; Treatment Failure; Young Adult

Topics: Aged; Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Rifampin

In 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees.. IGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0-17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up.. Screening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence.

Topics: Adolescent; Berlin; Chemoprevention; Female; Germany; Hepatitis B; Humans; Isoniazid; Latent Tuberculosis; Male; Mass Screening; Minors; Refugees; Rifampin; Tuberculosis

Latent tuberculosis infection (LTBI) treatment in persons at increased risk of disease progression is a key strategy with the strong potential to increase rate of tuberculosis (TB) decline in the United States. However, LTBI treatment in homeless persons, a population at high-risk of active TB disease, is usually associated with poor adherence. We describe the impact of using directly observed treatment (DOT) versus self-administered treatments (SAT) as an adherence-improving intervention to administer four months of daily rifampin regimen for LTBI treatment among homeless adults in Atlanta. Retrospective analysis of clinical care data on 274 homeless persons who initiated daily rifampin treatment for LTBI treatment at a county health department between January 2014 and December 2016 was performed. To reduce bias from non-random assignment of treatment, an inverse probability of treatment weighted (IPTW) logistic regression model was used to assess the effect of treatment type on treatment completion. Subgroup analyses were performed to assess heterogeneity of treatment effect on LTBI completion. Of 274 LTBI treatment initiators, 177 (65%) completed treatment [DOT 118/181 (65%), SAT 59/93 (63%)]. In the fully adjusted and weighted analysis, the odds of completing LTBI treatment on DOT was 40% higher than the odds of completing treatment by SAT [adjusted odds ratio (95% CI), aOR: 1.40 (1.07, 1.82), p = 0.014]. The unstable nature of homeless persons' lifestyle makes LTBI treatment difficult for many reasons. Our study lends support to the use of DOT to improve LTBI treatment completion among subgroups of homeless persons on treatment with daily rifampin.

Topics: Adult; Aged; Antibiotics, Antitubercular; Directly Observed Therapy; Female; Georgia; Humans; Ill-Housed Persons; Latent Tuberculosis; Male; Middle Aged; Propensity Score; Rifampin

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Resistance, Bacterial; Humans; Latent Tuberculosis; Rifampin; Treatment Outcome

In the province of Manitoba, Canada, given that latent tuberculosis infection (LTBI) treatment is provided at no cost to the patient, treatment completion rates should be optimal. The objective of this study was to estimate LTBI treatment completion using prescription drug administrative data and identify patient characteristics associated with completion.. Prescription drug data (1999-2014) were used to identify individuals dispensed isoniazid (INH) or rifampin (RIF) monotherapy. Treatment completion was defined as being dispensed INH for ≥ 180 days (INH180) or ≥ 270 days (INH270) or RIF for ≥ 120 days (RIF120). Logistic regression models tested socio-demographic and comorbidity characteristics associated with treatment completion.. The study cohort comprised 4985 (90.4%) persons dispensed INH and 529 (9.6%) RIF. Overall treatment completion was 60.2% and improved from 43.1% in 1999-2003 to 67.3% in 2009-2014. INH180 showed the highest completion (63.8%) versus INH270 (40.4%) and RIF120 (27.0%). INH180 completion was higher among those aged 0-18 years (68.5%) compared with those aged 19+ (61.0%). Sex, geography, First Nations status, income quintile, and comorbidities were not associated with completion.. Benchmark 80% treatment completion rates were not achieved in Manitoba. Factors associated with non-completion were older age, INH270, and RIF120. Access to shorter LTBI treatments, such as rifapentine/INH, may improve treatment completion.

Topics: Adolescent; Adult; Age Factors; Aged; Antitubercular Agents; Child; Child, Preschool; Databases, Factual; Female; Humans; Infant; Infant, Newborn; Isoniazid; Latent Tuberculosis; Male; Manitoba; Middle Aged; Prescription Drugs; Rifampin; Treatment Adherence and Compliance; Young Adult

Children less than 5 years of age have the highest age-specific rate of progression from latent tuberculosis infection (LTBI) to active disease. Therefore, regimens for treatment of pediatric LTBI must be not only efficacious but practical enough to overcome the unique childhood barriers to regimen adherence. Since 2012, a 4-month regimen of daily rifampin (4R) has been the standard recommendation for pediatric LTBI at the Denver Metro Tuberculosis Clinic.. Using univariate and multivariate analyses, we compared treatment completion rates between 4R and 9-month isoniazid (9H) regimens for all pediatric patients treated for LTBI at the Denver Metro Tuberculosis Clinic between January 1, 2006, and December 31, 2015, and assessed the influence of clinical and demographic characteristics on successful completion of the 2 regimens.. There were 395 children in the 4R cohort and 779 in the 9H cohort. Completion rates overall were significantly higher for 4R than 9H (83.5% vs. 68.8%, P < 0.001). Drug toxicity leading to treatment noncompletion was low in both groups (1.5% in 4R and 0.7% in 9H, P = 0.23), and no patient progressed to active tuberculosis in either cohort. The 9H cohort was more likely to fail treatment completion because of barriers potentially related to the longer duration of treatment such as relocation or loss to follow-up.. Pediatric patients were significantly more likely to complete LTBI treatment using a 4R than with a 9-month isoniazid regimen. Better completion rates of 4R may increase efficacy of tuberculosis prevention and decrease demand on public health resources.

Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Infant; Infant, Newborn; Latent Tuberculosis; Male; Odds Ratio; Population Surveillance; Rifampin; Treatment Failure; Treatment Outcome; United States

Isoniazid monotherapy for six or nine months and the combination of isoniazid and rifampicin for three or four months are the most used regimens for treating latent tuberculosis. The main aim of this retrospective study is to evaluate the safety of latent tuberculosis treatment by analysing side effects in both regimens.. Children with latent tuberculosis and treated with isoniazid or isoniazid and rifampicin were included. Periodic evaluations with clinical assessment and blood exams were carried out to detect any adverse reaction, including elevated serum transaminases.. 441 children were included, 14.5% treated with isoniazid and 85.5% with isoniazid and rifampicin. Five patients under combined treatment developed hepatotoxicity within the first month. None of the patients under isoniazid monotherapy presented hepatotoxicity. A slight increase of transaminases level was found in both groups (18.7% in isoniazid and 10.3% in isoniazid/rifampicin groups, respectively) without causing discontinuation of treatment, with values normalization at the subsequent checks.. Both regimens resulted safe. Hepatotoxicity occurred rarely and within the first month. For this reason, it may be appropriate to perform liver function tests after about one month from the beginning of therapy to avoid diagnostic delays.

Topics: Adolescent; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Isoniazid; Latent Tuberculosis; Liver Function Tests; Male; Retrospective Studies; Rifampin; Time Factors; Transaminases

To describe the clinical features of patients with uveitis associated with latent tuberculosis (TB) and examine the effect of anti-TB treatment (ATT) on uveitis outcome.. Retrospective cohort study.. One hundred ninety-nine eyes of 129 patients diagnosed with uveitis associated with latent TB were evaluated for recurrence of disease following treatment. Eighty-nine of the patients (69%) received ATT and information was gathered retrospectively regarding clinical outcome, vision, and treatment. Outcome measures included best-corrected visual acuity (BCVA) and rate of disease recurrence.. This study included 89 patients (69%) who received ATT and 40 patients who did not. The uveitis was treated with local and systemic anti-inflammatory and immunosuppressive therapy in all patients. The mean change in BCVA following treatment was 4.5 ± 1.4 letters over the follow-up period, with no difference between eyes of patients receiving ATT and those who did not. Sixty-eight eyes (34.9%) had a recurrence of uveitis (0.64 ± 0.08 recurrences per year), with eyes of patients receiving ATT less likely to develop a recurrence compared to those not receiving ATT (29.5% vs 48.2%, odds ratio 0.47, 95% confidence interval 0.29-0.77, P = .003). Eyes treated with ATT recurred at an estimated median of 120 months, compared with 51 months in eyes with no treatment (P = .005).. Treatment with ATT halved the risk of uveitis recurrence and delayed the onset of the first recurrence in eyes with uveitis associated with latent TB.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Child; Child, Preschool; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Pyrazinamide; Recurrence; Retrospective Studies; Rifampin; Treatment Outcome; Tuberculosis, Ocular; Uveitis; Visual Acuity

Topics: Aged; Antitubercular Agents; Arthritis, Rheumatoid; Drug Administration Schedule; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin

The standard drugs used to treat tuberculosis are rifampicin and isoniazid. These agents are usually safe and inexpensive for short-term use in treatment of latent tuberculosis infection, but sometimes cause adverse renal effects, including minimal change disease (MCD).. Here, we report a 51-year-old woman with latent tuberculosis infection who developed nephrotic syndrome during treatment with rifampicin and isoniazid for 25 days.. Renal biopsy findings were compatible with MCD, and she had no relevant medical history and was not taking other medications. A diagnosis of anti-tuberculosis drug- induced MCD was made. This is the first report of acute renal failure due to rifampicin and/or isoniazid-induced MCD.. After cessation of rifampicin and isoniazid, however, acute renal failure progressed and she was treated with temporary dialysis and oral prednisolone.. The patient achieved complete remission after cessation of rifampicin and isoniazid with steroid therapy.. This case demonstrates that rifampicin and/or isoniazid can cause nephrotic syndrome with acute renal failure during the first months of continuous latent tuberculosis therapy. Therefore, renal function and proteinuria should be monitored carefully in all patients taking rifampicin and isoniazid, especially during the first few months of therapy.

Topics: Acute Kidney Injury; Antitubercular Agents; Female; Glucocorticoids; Humans; Isoniazid; Latent Tuberculosis; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisolone; Proteinuria; Remission Induction; Renal Dialysis; Rifampin; Treatment Outcome

Treatment of latent tuberculosis infection (LTBI) is critical to the control and elimination of tuberculosis disease (TB) in the United States. In 2011, CDC recommended a short-course combination regimen of once-weekly isoniazid and rifapentine for 12 weeks (3HP) by directly observed therapy (DOT) for treatment of LTBI, with limitations for use in children aged <12 years and persons with human immunodeficiency virus (HIV) infection (1). CDC identified the use of 3HP in those populations, as well as self-administration of the 3HP regimen, as areas to address in updated recommendations. In 2017, a CDC Work Group conducted a systematic review and meta-analyses of the 3HP regimen using methods adapted from the Guide to Community Preventive Services. In total, 19 articles representing 15 unique studies were included in the meta-analysis, which determined that 3HP is as safe and effective as other recommended LTBI regimens and achieves substantially higher treatment completion rates. In July 2017, the Work Group presented the meta-analysis findings to a group of TB experts, and in December 2017, CDC solicited input from the Advisory Council for the Elimination of Tuberculosis (ACET) and members of the public for incorporation into the final recommendations. CDC continues to recommend 3HP for treatment of LTBI in adults and now recommends use of 3HP 1) in persons with LTBI aged 2-17 years; 2) in persons with LTBI who have HIV infection, including acquired immunodeficiency syndrome (AIDS), and are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine; and 3) by DOT or self-administered therapy (SAT) in persons aged ≥2 years.

Topics: Adolescent; Antibiotics, Antitubercular; Centers for Disease Control and Prevention, U.S.; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Rifampin; United States

Anti-tuberculosis formulations necessitate uninterrupted treatment to cure tuberculosis (TB), but are characterised by suboptimal adherence, which jeopardises therapeutic efficacy. Long-acting injectable (LAI) formulations or implants could address these associated issues.. niazid, rifapentine, bedaquiline and delamanid-in adults for treatment for latent tuberculous infection (LTBI).. PBPK models were developed and qualified against available clinical data by integrating drug physicochemical properties and in vitro and population pharmacokinetic data into a mechanistic description of drug distribution. Combinations of optimal dose and release rates were simulated such that plasma concentrations were maintained over the epidemiological cut-off or minimum inhibitory concentration for the dosing interval.. The PBPK model identified 1500 mg of delamanid and 250 mg of rifapentine as sufficient doses for monthly intramuscular administration, if a formulation or device can deliver the required release kinetics of 0.001-0.0025 h-1 and 0.0015-0.0025 h-1, respectively. Bedaquiline and isoniazid would require weekly to biweekly intramuscular dosing.. We identified the theoretical doses and release rates of LAI anti-tuberculosis formulations. Such a strategy could ease the problem of suboptimal adherence provided the associated technological complexities for LTBI treatment are addressed.

Topics: Adolescent; Adult; Antitubercular Agents; Diarylquinolines; Drug Administration Schedule; Drug Liberation; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Nitroimidazoles; Oxazoles; Proof of Concept Study; Rifampin; Treatment Outcome; Young Adult

Topics: Adult; Aged; Antitubercular Agents; Biological Products; Chemoprevention; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Prevalence; Psoriasis; Retrospective Studies; Rifampin; Tuberculin Test

To evaluate the acceptance of, adherence to, and outcomes of latent tuberculous infection (LTBI) treatment among health care workers (HCWs).. This was a retrospective study in a tertiary hospital in Korea. From May to August 2017, 2190 HCWs simultaneously underwent a tuberculin skin test (TST) and interferon-gamma release assay (IGRA). LTBI was diagnosed if the TST induration was 10 mm or IGRA results were positive.. Of 2190 HCWs tested, 1006 (45.9%) were diagnosed with LTBI. Of these, 655 (65.1%) HCWs visited out-patient clinics, 234 (35.7%) of whom were advised treatment by physicians. Among these, 120 (51.3%) accepted the physicians' recommendations. In general, HCWs who were older, male and smoked were less likely to visit out-patient clinics. Sixty (50%) HCWs received 3 months of isoniazid plus rifampicin (3HR) and 57 (47.5%) HCWs received 4 months of rifampicin (4R). The proportion of HCWs with 2 side effects (3HR 20% vs. 4R 7.0%,. Overall, the acceptance and completion rate for LTBI treatment was not adequate. For effective LTBI management in HCWs, further programmatic strategies are needed.

Topics: Adult; Antibiotics, Antitubercular; Drug Administration Schedule; Drug Therapy, Combination; Female; Health Personnel; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Republic of Korea; Retrospective Studies; Rifampin; Tertiary Care Centers; Tuberculin Test; Young Adult

Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016.. This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson's chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects.. We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals.. We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Child; Child, Preschool; Female; Humans; Incidence; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Norway; Prospective Studies; Rifampin; Young Adult

Since January 2013, the New York City (NYC) Health Department Tuberculosis (TB) Program has offered persons diagnosed with latent TB infection (LTBI) the 3-month, once-weekly isoniazid and rifapentine (3HP) treatment regimen. Patients on this treatment are monitored in-person under directly observed therapy (DOT). To address patient and provider barriers to in-person DOT, we piloted the use of a videoconferencing software app to remotely conduct synchronous DOT (video directly observed therapy; VDOT) for patients on 3HP.. The objective of our study was to evaluate the implementation of VDOT for patients on 3HP and to assess whether treatment completion for these patients increased when they were monitored using VDOT compared with that using the standard in-person DOT.. Between February and October 2015, patients diagnosed with LTBI at any of the four NYC Health Department TB clinics who met eligibility criteria for treatment with 3HP under VDOT (V3HP) were followed until 16 weeks after treatment initiation, with treatment completion defined as ingestion of 11 doses within 16 weeks. Treatment completion of patients on V3HP was compared with that of patients on 3HP under clinic-based, in-person DOT who were part of a prior study in 2013. Furthermore, outcomes of video sessions with V3HP patients were collected and analyzed.. During the study period, 70% (50/71) of eligible patients were placed on V3HP. Treatment completion among V3HP patients was 88% (44/50) compared with 64.9% (196/302) among 3HP patients on clinic DOT (P<.001). A total of 360 video sessions were conducted for V3HP patients with a median of 8 (range: 1-11) sessions per patient and a median time of 4 (range: 1-59) minutes per session. Adherence issues (eg, >15 minutes late) during video sessions occurred 104 times. No major side effects were reported by V3HP patients.. The NYC TB program observed higher treatment completion with VDOT than that previously seen with clinic DOT among patients on 3HP. Expanding the use of VDOT may improve treatment completion and corresponding outcomes for patients with LTBI.

Topics: Adult; Ambulatory Care Facilities; Antitubercular Agents; Data Collection; Directly Observed Therapy; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin; Telemedicine; Videoconferencing; Young Adult

Topics: Aged; Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Treatment for latent tuberculous infection (LTBI) is a key strategy for the elimination of tuberculosis. Rare adverse reactions associated with LTBI treatment have been reported. We report the only case of acute kidney injury reported to Centers for Disease Control and Prevention surveillance for LTBI treatment-related adverse events. The patient experienced rapid intravascular hemolysis, resulting in heme pigment nephropathy; he was hospitalized and received three hemodialysis treatments, but recovered without sequelae. While LTBI treatment-related adverse events are rare, health care providers should maintain clinical vigilance and regularly counsel patients to facilitate prompt diagnoses and effective clinical management of affected patients.

Topics: Acute Kidney Injury; Adult; Antibiotics, Antitubercular; Humans; Latent Tuberculosis; Male; Renal Dialysis; Rifampin

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Native Hawaiian or Other Pacific Islander; Northern Territory; Odds Ratio; Rifampin; White People; Young Adult

Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is spread from person to person through the air. TB can be spread in congregate settings, such as school environments, to varying degrees, based on factors including duration of contact and air ventilation (1); therefore, evaluating potential contacts and exposures can be challenging. In February 2015, a student at a Kansas high school received a diagnosis of active pulmonary TB disease. Screening of 385 (91%) school contacts, four (100%) household contacts, and 19 (90%) social contacts resulted in the identification of 50 persons with latent TB infection. Johnson County Department of Health and Environment (JCDHE) Public Health Emergency Preparedness personnel used their experience with points of distribution logistics to optimize testing clinic layouts and implement the incident command structure. Open communication with students, school staff members, the public, and the media about the investigation from the outset was imperative to reduce rumors and unease that can accompany a large communicable disease investigation. The large number of persons needing treatment for latent TB overwhelmed JCDHE's two TB nurses. As a result, JCDHE developed a policy and procedure to allow persons who met eligibility requirements to complete 12 weekly doses of isoniazid and rifapentine treatment using video directly observed therapy (VDOT) rather than traditional in-person directly observed therapy (DOT). This procedure facilitated treatment compliance and completion; among the eligible 15 persons who chose the 12-week VDOT option, 14 (93%) completed treatment. State and local health departments might consider use of VDOT to monitor treatment of persons with latent TB infection.

Topics: Antitubercular Agents; Contact Tracing; Directly Observed Therapy; Humans; Isoniazid; Kansas; Latent Tuberculosis; Mycobacterium tuberculosis; Patient Compliance; Rifampin; Schools; Telemedicine; Treatment Outcome; Videoconferencing

Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings.. Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation.. Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment.. Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Ill-Housed Persons; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Rifampin; Students; United States; Young Adult

There are 8.6 million cases of active tuberculosis (TB) worldwide, and an estimated one-third of the world population has latent tuberculosis infection (LTBI). In the United States, up to 80% of active cases may be caused by untreated reactivated latent infection. A case of TB can spread rapidly impacting the readiness of a unit. To prevent the development of TB, it is critical that active duty service members with LTBI complete treatment. The use of isoniazid (INH) and rifapentine (RPT) as a directly observed therapy (DOT) treatment option was recommended by the Centers for Disease Control and Prevention in late 2011. Since then, there have been limited studies on the use of this treatment regimen in a civilian clinic setting and to our knowledge no studies within a military setting.. This study compares the completion rate of LTBI treatment in 2 military public health clinics, using a retrospective chart review of 179 subjects who attempted treatment with INH/RPT DOT and 186 with the non-INH/RPT non-DOT regimen.. When compared to other LTBI regimens completed or attempted in this period, completion rates were higher in INH/RPT DOT regimens. The INH/RPT DOT treatment regimen allowed enough flexibility with completion between 11 and 16 weeks for active duty service members to increase completion to 94.6%, compared to 73% in the non-INH/RPT regimen.. This project demonstrated the feasibility of INH/RPT DOT treatment within the military population resulting in a higher completion rate than the non-INH/RPT non-DOT regimen. The use of the INH/RPT DOT regimen should be considered for use in all military or similar populations.

Topics: Adolescent; Adult; Ambulatory Care Facilities; Antitubercular Agents; Directly Observed Therapy; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Military Personnel; Retrospective Studies; Rifampin; United States

The risk of infection with Mycobacterium tuberculosis among healthcare workers (HCWs) is estimated to be higher than the general population. However, HCW acceptance and compliance with available latent tuberculosis infection (LTBI) treatment regimens has been problematic. Recently, regimens have become available that might improve HCW acceptance and compliance with LTBI treatment.. A retrospective single-center review of Employee Health and Wellness Services records of all HCWs diagnosed with LTBI was conducted. HCWs diagnosed with LTBI were offered 9-month isoniazid (INH), 4-month rifampin (RIF), weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no treatment. Acceptance, completion rates, and side effects were reported for each regimen. Comparisons of regimens were assessed using Fisher exact test.. Between 2005 and 2014, 363 of 927 (39%) HCWs diagnosed with LTBI accepted treatment. Of 363, 202 chose INH, 106 RIF, and 55 RPT/INH. Completion rates for each regimen were 58%, 80%, and 87%, respectively. HCWs were significantly more likely to have completed treatment with RIF (P < .0001) or RPT/INH (P < .0001) than INH. Rates of discontinuation owing to side effects were 35% for INH, 21% for RIF, and 10% for RPT/INH. Discontinuation of therapy due to side effects was significantly more frequent in the INH than the RPT/INH group (P = .0042).. Completion of RIF and RPT/INH for LTBI in an HCW population is more likely than INH. Rates of discontinuation due to side effects were lower among those taking RPT/INH. Shorter LTBI treatment regimens should be more widely considered for HCWs in the United States.

Topics: Adult; Antitubercular Agents; Disease Management; Drug Therapy, Combination; Female; Health Personnel; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Retrospective Studies; Rifampin

The primary role of any tuberculosis (TB) control program is to ensure the prompt identification and effective treatment of active disease. The host immune system often succeeds in containing the initial (or primary) infection with Mycobacterium tuberculosis (Mtb), but may fail to eliminate the pathogen. The persistence of viable organisms explains the potential for the development of active disease years or even decades after infection. This is known as latent tuberculosis infection (LTBI) although, rather than a distinct entity, this probably represents part of a dynamic spectrum. Individuals with LTBI are asymptomatic and it is therefore clinically undetectable. The World Health Organization (WHO) estimates that one-third of the global population has been infected with Mtb, with highest prevalence of LTBI in countries/regions with the highest prevalence of active disease. In 2013, 88% of 1322 notifications in Australia were in the overseas-born population (incidence 19.5 per 100,000 v. 1.0 per 100,000), with this proportion rising over the course of the last decade. Combined with epidemiological evidence of low local transmission, this strongly implies that the vast majority resulted from reactivation of latent infection acquired prior to immigration. Contrasting trends in TB incidence in other developed countries probably reflect differences in policy regarding LTBI.. The diagnosis and treatment of LTBI represents an important opportunity for intervention by jurisdictional TB control programs.

Topics: Antitubercular Agents; Australia; Chemoprevention; Communicable Disease Control; Disease Notification; Drug Combinations; Emigration and Immigration; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Prevalence; Rifampin; Transients and Migrants; Tuberculin Test; Tuberculosis, Pulmonary

Renal transplant candidates (RTC) with latent tuberculosis infection (LTBI) are at significant risk for tuberculosis reactivation. Twelve-week rifapentine (RPT)/isoniazid (INH) is effective for LTBI but clinical experience in RTC is scarce.. We conducted a retrospective study of RTC with LTBI treated with either 12-week RPT/INH or 9-month INH from March 1, 2012, through February 28, 2014. We evaluated both groups for differences in rates of treatment completion, monthly follow-up visit compliance, transaminase elevations, and adverse reactions leading to discontinuation of LTBI treatment. The utility of weekly reminders was also evaluated in the 12-week regimen. Direct observed therapy was not performed in our study.. Of 153 patients, 43 (28%) and 110 (72%) were started on 12-week RPT/INH and 9-month INH, respectively. The treatment completion and monthly follow-up visit compliance rates were higher in the 12-week RPT/INH group (40 [93%] vs 52 [47%], P < 0.001) and (11/40 [28%] vs 13/104 [13%], P = 0.03), respectively. Transaminase elevations were not observed in the RPT/INH group, but occurred in 6 (5%) of the INH group. There were no differences in adverse reactions leading to discontinuation of LTBI treatment.. Twelve-week RPT/INH appears to be an excellent choice for LTBI in RTC. It has a higher treatment completion rate and causes less transaminase elevations, and weekly reminders may be an alternative when direct observed therapy is not feasible.

Topics: Adult; Aged; Antitubercular Agents; Biomarkers; Chemical and Drug Induced Liver Injury; Choice Behavior; Drug Therapy, Combination; Female; Humans; Isoniazid; Kidney Diseases; Kidney Transplantation; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Reminder Systems; Retrospective Studies; Rifampin; Time Factors; Transaminases; Treatment Outcome; Treatment Refusal; Up-Regulation; Waiting Lists

The United States has a low burden of drug resistance among tuberculosis (TB) cases compared with other world regions. TB is increasingly concentrated among foreign-born individuals who have higher rates of drug resistance than U.S.-born individuals. While universal drug susceptibility testing is the standard for detecting active tuberculosis, there are limited guidelines for latent tuberculosis infection (LTBI) treatment based on risk factors for drug resistance. To quantify the variable risk of drug resistance among foreign-born individuals, all TB cases in Washington State between 1994 and 2014 with drug resistance data for isoniazid, rifampin, pyrazinamide, and ethambutol were divided into eight regions of birth. Logistic regression was used to characterize regional differences in resistance patterns. Genotypic cluster and lineage data were compared against drug resistance in a subanalysis. Among 4,298 cases, isoniazid resistance was more common in foreign-born individuals (12.6% versus 4.8%;

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Child; Child, Preschool; Drug Resistance, Bacterial; Ethambutol; Female; Humans; Infant; Infant, Newborn; Isoniazid; Latent Tuberculosis; Logistic Models; Male; Mexico; Middle Aged; Multivariate Analysis; Philippines; Pyrazinamide; Rifampin; Risk Factors; Vietnam; Washington; Young Adult

The current recommendation for the treatment of latent tuberculosis infection (LTBI) in solid organ transplant candidates is isoniazid for 9 months, but this treatment has the main problem of frequently reaching the posttransplant period.. This is the study of efficacy and safety of a 3-month regimen with isoniazid and rifampicin (3HR) in lung transplant candidates in the Reina Sofía Hospital in Córdoba.. Three hundred and ninety-eight lung transplant patients were evaluated. Ninety-two (24.9%) had LTBI and just 22 received the 3HR treatment. One additional patient was treated because he had a history of previous incomplete treatment for active TB. None of the treated patients developed posttransplant tuberculosis compared to three of the 62 patients with LTBI who were not treated (4.8%). Three patients could not conclude the 3HR treatment (13%), but only two had adverse effects (8.7%).. Treatment of LTBI in lung transplant candidates using a short course of 3HR appears to be effective and safe in preventing posttransplant TB in lung transplant recipients.

Topics: Antibiotics, Antitubercular; Antitubercular Agents; Female; Follow-Up Studies; Humans; Isoniazid; Latent Tuberculosis; Lung Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Retrospective Studies; Rifampin; Risk Factors

Topics: Adult; Aged; Antitubercular Agents; Blood Pressure; Cohort Studies; Drug Therapy, Combination; Humans; Hypertension; Isoniazid; Kidney Transplantation; Latent Tuberculosis; Middle Aged; Rifampin; Time Factors; Transplant Recipients

The U.S. Centers for Disease Control and Prevention (CDC) recommended a new regimen for treatment of latent tuberculosis (three months of weekly isoniazid and rifapentine) in late 2011. While completion rates of this regimen were reported to be higher than nine months of isoniazid, little is known about the completion rates of three months of isoniazid and rifapentine compared to nine months of isoniazid or four months of rifampin in actual use scenarios.. We conducted a retrospective cohort study comparing treatment completion for latent tuberculosis (TB) infection in patients treated with nine months of isoniazid, three months of isoniazid and rifapentine or four months of rifampin in outpatient clinics and a public health TB clinic in Seattle, Washington. The primary outcome of treatment completion was defined as 270 doses of isoniazid within 12 months, 120 doses of rifampin within six months and 12 doses of isoniazid and rifapentine within four months.. Three hundred ninety-three patients were included in the study. Patients were equally likely to complete three months of weekly isoniazid and rifapentine or four months of rifampin (85% completion rate of both regimens), as compared to 52% in the nine months of isoniazid group (p < 0.001). These associations remained statistically significant even after adjusting for clinic location and type of monitoring. Monitoring type (weekly versus monthly versus less often than monthly) had less impact on treatment completion than the type of treatment offered.. Patients were equally as likely to complete the three months of isoniazid and rifapentine as four months of rifampin. Four months of rifampin is similar in efficacy compared to placebo as isoniazid and rifapentine but does not require directly observed therapy (DOT), and is less expensive compared to combination therapy with isoniazid and rifapentine, and thus can be the optimal treatment regimen to achieve the maximal efficacy in a community setting.

Topics: Adult; Antitubercular Agents; Centers for Disease Control and Prevention, U.S.; Directly Observed Therapy; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Patient Compliance; Retrospective Studies; Rifampin; United States; Washington

The treatment of latent tuberculous infection (TBI) is a productive and meaningful approach to tuberculosis (TB) control, and an important component of the World Health Organization's (WHO's) new End TB Strategy, especially in high-risk contacts. Unfortunately, although recognized and recommended by the WHO, it continues to be underutilized, and has even been ignored for decades in some high-risk groups, as though it were a taboo. Historical approaches to treating TBI in contacts of drug-susceptible and drug-resistant TB are presented and discussed as compelling experiences. In the United States, the Centers for Disease Control and Prevention have recently shown that a directly observed or even self-administered 12-month regimen to treat TBI with once-weekly isoniazid (INH) and rifapentine is as effective as 9 months of daily INH. Treating TBI in drug-susceptible cases and their contacts should not still be considered taboo-such a short, effective regimen is more akin to the Holy Grail. While not yet confirmed in a clinical trial, treating contacts of drug-resistant TB with the same drugs that are effective in the source case would be expected intuitively and practically to prevent TB in contacts and should be introduced now instead of waiting until clinical trials are completed.

Topics: Antitubercular Agents; Contact Tracing; Drug Therapy, Combination; Global Health; Humans; Isoniazid; Latent Tuberculosis; Rifampin; Taboo; Time Factors; Tuberculosis; World Health Organization

Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited.. Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers.. Eleven patients were men, and the median age was 60 years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation.. Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

Topics: Adult; Aged; Antibiotics, Antitubercular; Directly Observed Therapy; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; New York; Rifampin

Herein, we report the discovery and structure-activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding in vitro activity against Mycobacterium tuberculosis CNCTC My 331/88 and six multidrug-resistant clinically isolated strains of M. tuberculosis, with minimum inhibitory concentration values as low as 0.03 μM (0.011-0.026 μg/mL). The investigated compounds had a highly selective antimycobacterial effect because they showed no activity against the other bacteria or fungi tested in this study. Furthermore, the investigated compounds exhibited low in vitro toxicities in four proliferating mammalian cell lines and in isolated primary human hepatocytes. Several in vitro genotoxicity assays indicated that the selected compounds have no mutagenic activity. The oxadiazole and thiadiazole derivatives with the most favorable activity/toxicity profiles also showed potency comparable to that of rifampicin against the nonreplicating streptomycin-starved M. tuberculosis 18b-Lux strain, and therefore, these derivatives, are of particular interest.

Topics: Animals; Antitubercular Agents; Bacteria; Cell Line; Cell Survival; Drug Design; Drug Resistance, Multiple, Bacterial; Fungi; Humans; Latent Tuberculosis; Microbial Sensitivity Tests; Microsomes; Mutagens; Mycobacterium tuberculosis; Oxazoles; Primary Cell Culture; Rifampin; Structure-Activity Relationship; Thiadiazoles

Twenty-four quinoxaline derivatives were evaluated for their antimycobacterial activity using BacTiter-Glo microbial cell viability assay. Five compounds showed MIC values <3.1 μM and IC50 values<1.5 μM in primary screening and therefore, they were moved on for further evaluation. Compounds 21 and 18 stand out, showing MIC values of 1.6 μM and IC50 values of 0.5 and 1.0 μM, respectively. Both compounds were the most potent against three evaluated drug-resistant strains. Moreover, they exhibited intracellular activity in infected macrophages, considering log-reduction and cellular viability. In addition, compounds 16 and 21 were potent against non-replicating Mycobacterium tuberculosis and compound 21 was bactericidal. Therefore, quinoxaline derivatives could be considered for making further advances in the future development of antimycobacterial agents.

Topics: Animals; Antitubercular Agents; Cell Line; Cyclic N-Oxides; Drug Resistance, Multiple, Bacterial; Latent Tuberculosis; Mice; Mycobacterium tuberculosis; Quinoxalines; Tuberculosis, Multidrug-Resistant

To investigate the outcome of rifam- picin (RFP) monotherapy for latent tuberculosis infection (LTBI) and the incidence of RFP-induced liver toxicity. [Method] We conducted a retrospective chart review of patients who received RFP monotherapy as LTBI treatment at the Daiichi Dispensary Clinic. [Result] Of 61 patients who received RFP monotherapy, the treatment completion rate was 88.5%, self-termination rate was 3.3%, abandonment rate due to adverse drug effects was 8.2% (5 cases: 3 cases of skin eruption and 2 cases of liver dysfunction). Among the 2 cases of liver dysfunction, I was not associated with abnormal alkaline phosphatase (ALP) or gamma-glutamyl transferase (y GTP) levels. Among patients with liver dysfunction who did not discontinue RFP mono- therapy, no cases-of severely abnormal ALP and/or y GTP levels were reported. [Conclusion] The incidence of liver toxicity due to RFP is lower than that observed with isoniazid, and liver dysfunction due to RFP was not always associated with abnormal of ALP and/or yGTP levels.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Latent Tuberculosis; Male; Middle Aged; Retrospective Studies; Rifampin; Young Adult

More than 25% of the world population has been infected with tuberculosis (TB), however only 10% of those infected will ever develop active disease. Clinically significant disease occurs through progression of primary infection or through later reactivation of latent TB infection (LTBI); this is most likely to occur in the first few years following infection, although late reactivation can occur several decades later, particularly in individuals who become immunosuppressed. Risk of TB acquisition is increased in people who have come to the UK from high incidence countries or who are born in the UK but come from high-risk ethnic minority groups. In 2015, 73% of those diagnosed with active TB were born outside the UK. Other risk groups include those who are homeless, in prison or who misuse drugs or alcohol. Once infected people who are immunosuppressed are at greater risk of progression to active disease. Infants below the age of 12 months can develop rapidly progressive and potentially fatal infection. Initial clinical assessment with chest radiography and the collection of three deep respiratory samples for smear microscopy and culture remain the standard of care. The management of active TB has not changed significantly over many years. The most significant changes in the 2016 NICE guidance relate to screening for LTBI in individuals who are contacts of a patient with active TB, or who are recent entrants to the UK from a high incidence country. NICE recommends that only contacts of patients with active pulmonary or laryngeal TB be screened.

Topics: Antitubercular Agents; Contact Tracing; Humans; Isoniazid; Latent Tuberculosis; Mass Screening; Practice Guidelines as Topic; Radiography, Thoracic; Rifampin; Tuberculosis, Pulmonary

[Purpose] To conduct a literature review on clin- ical studies and national guidelines in various countries, for the purposes of facilitating discussion regarding whether latent tuberculosis infection (LTBI) treatment regimens com- posed of isoniazid and rifampicin should be introduced in Japan. [Methods] For clinical studies, 23 non-randomized studies and 10 randomized studies in the literature were reviewed. [Results] In patients who had received treatments com- posed of isoniazid and rifampicin ([HR]; largely 3 months), compared with those who had received isoniazid monother- apy ([H]; largely 6 to 9 months), both frequency and sever- ity of liver dysfunction tended to be reduced, but adverse drug effects increased in general. Treatment completion rate tended to be higher in those who had received HR than in those who had received H. Preventive effects of HR seemed to be at least equivalent, or somewhat superior, to H. Many national guidelines of the European Union and other coun- tries reviewed in this study recommended HR as an LTBI treatment regimen, and generally provided a high level of evidence. [Conclusion] 3HR treatment has been well studied in many clinical and randomized studies, and seems to have garnered a high level of merit in order to be introduced as one of the LTBI treatment regimens in Japan.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Isoniazid; Latent Tuberculosis; Middle Aged; Rifampin; Treatment Outcome; Young Adult

Completion of treatment for tuberculosis infection (TBI) with 9 months of self-administered daily isoniazid (9H) has historically been low (<50%) among New York City (NYC) Health Department tuberculosis clinic patients. Treatment of TBI with 3 months of once-weekly isoniazid and rifapentine (3HP) administered under directly observed therapy (DOT) might increase treatment acceptance and completion.. The study population included patients diagnosed with TBI at 2 NYC Health Department tuberculosis clinics from January 2013 through November 2013. Treatment acceptance and completion with 3HP were compared with historical estimates. Treatment outcomes, side effects, and reasons for refusing 3HP were described.. Among 631 patients eligible for TBI treatment, 503 (80%) were offered 3HP; 302 (60%) accepted, 92 (18%) chose other treatment, and 109 (22%) refused treatment. The most common reason for refusing 3HP was the clinic-based DOT requirement. Forty (13%) patients treated with 3HP experienced side effects--9 were restarted on 3HP, 18 switched treatment regimens, and 13 discontinued. Although treatment acceptance did not differ from historical estimates (78% vs 79%, P = .75), treatment completion increased significantly (65% vs 34%, P < .01).. Implementation of 3HP in 2 NYC Health Department tuberculosis clinics increased TBI treatment completion by 31 percentage points compared with historical estimates. More flexible DOT options may improve acceptance of 3HP. Wider use of 3HP may substantially improve TBI treatment completion in NYC and advance progress toward tuberculosis elimination.

Topics: Adult; Ambulatory Care Facilities; Antitubercular Agents; Directly Observed Therapy; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; New York City; Patient Compliance; Public Health; Rifampin; Young Adult

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events.In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation.Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events.Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40-60%.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Child; Child, Preschool; Communicable Disease Control; Female; Health Policy; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Infant, Newborn; Infectious Disease Medicine; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Multivariate Analysis; Netherlands; Registries; Rifampin; Rural Population; Treatment Outcome; Tuberculosis; Young Adult

Objectives. Approximately 65 percent of tuberculosis (TB) cases in Canada each year occur from reactivation in foreign-born individuals. Refugees are at high risk after immigration. Routine screening of this population for latent TB infection (LTBI) is generally considered infeasible. We evaluated the outcome of LTBI screening and treatment amongst refugees. Methods. Government-sponsored refugees in Edmonton are seen at the New Canadians' Clinic and screened for TB and LTBI. We reviewed records of patients between 2009 and 2011. Completeness of initial assessment, diagnosis of latent infection, and completion of LTBI treatment were evaluated. Treatment for LTBI was offered when patients had a positive Tuberculin Skin Test (TST) and risk factors for progression to TB. An Interferon-Gamma Release Assay (IGRA) was performed on all other TST positives; treatment is only offered if it was positive. Results. 949 refugees were evaluated. 746 TSTs were read, with 265 positive individuals. IGRA testing was performed in 203 TST positive individuals without other TB risk factors; 110 were positive. LTBI treatment was offered to 147 of 151 eligible patients, 141 accepted, and 103 completed a treatment course. Conclusion. We observed high proportions of patient retention, completion of investigations, and treatment. This care model promises to be a component of effective TB prevention in this high-risk population.

Topics: Adolescent; Adult; Alberta; Ambulatory Care; Antitubercular Agents; Canada; Child; Disease Eradication; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Mass Screening; Middle Aged; Refugees; Rifampin; Tuberculin Test; Young Adult

Donor-derived tuberculosis (TB) is an increasingly recognized complication of solid organ transplantation. We report a case of isoniazid-resistant pulmonary TB in a lung transplant recipient. The patient acquired the infection from the lung donor who was previously empirically treated with isoniazid for latent TB. The case highlights the caveat that, while adequate treatment of latent TB with isoniazid is presumed, meticulous screening of donors is required.

Topics: Adult; Allografts; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antitubercular Agents; Bacteremia; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Fluoroquinolones; Humans; Immunosuppression Therapy; Isoniazid; Latent Tuberculosis; Lung Transplantation; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium tuberculosis; Pseudomonas aeruginosa; Rifampin; Tissue Donors; Tuberculosis, Pulmonary

Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P <0.001). The cost of 3HP and 9H was US$261.24 and US$717.3, respectively. The cost-effectiveness ratio with isoniazid for 9 months was US$ 15392/avoided 1 case of tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Cost-Benefit Analysis; Directly Observed Therapy; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Pilot Projects; Rifampin; Taiwan; Time Factors; Tuberculosis, Pulmonary; Young Adult

Topics: Antitubercular Agents; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin

A tertiary referral centre in South Korea.. To compare the completion rates and adverse drug reactions of three latent tuberculous infection (LTBI) treatment regimens for patients receiving anti-tumour necrosis factor (anti-TNF) therapy.. A total of 408 patients were diagnosed with LTBI before receiving anti-TNF therapy between December 2004 and December 2013. Nine months of isoniazid (9H), 4 months of rifampicin (4H) or 3 months of isoniazid/rifampicin (3HR) were prescribed. The results were analysed retrospectively.. The mean age of the 408 study subjects was 44 years; 258 (63.2%) were male. The 9H, 4R and 3HR treatment regimens were given to respectively 61 (15.0%), 139 (34.1%) and 208 (51.0%) patients. A total of 362 (88.7%) patients completed the treatment. The treatment completion rate was highest in patients receiving 3HR (94.2%). Of the 408 patients, 54 (13.2%) had one or more adverse drug reactions; their frequency was similar in the three groups.. In patients receiving anti-TNF therapy, 3HR seems to be the most acceptable treatment regimen for LTBI, given its high completion rate and acceptable rate of adverse drug reactions.

Topics: Adult; Antibiotics, Antitubercular; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Republic of Korea; Retrospective Studies; Rifampin; Tumor Necrosis Factor-alpha

Treating latent tuberculosis infection is a strategy for eliminating tuberculosis, and isoniazid is recommended as preventive therapy. However, concerns have been raised regarding the application of isoniazid due to its toxicity, particularly hepatotoxicity; however, biochemical monitoring is not routinely performed during treatment. We herein present a case of fatal isoniazid-induced acute liver failure. The patient's liver function was not periodically examined and isoniazid therapy was continued for 10 days despite the onset of symptoms associated with hepatitis. The patient died four months after hospitalization. It is essential to consider the potential toxicities of isoniazid and establish strategies to prevent acute liver failure.

Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Hospitalization; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin

Topics: Antitubercular Agents; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin

Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin

Short-course directly observed isoniazid plus rifapentine (INH/RPT) combination could have potential advantages over a standard 9-month INH regimen for the treatment of latent tuberculosis infection in solid-organ transplant (SOT) candidates.. We prospectively assessed the safety and tolerability of 12 weeks of INH/RPT given directly observed therapy in 17 consecutive SOT candidates with latent tuberculosis infection.. The median age was 57 years and 82% were men. Of the 17 patients, 13 (76%) successfully completed therapy and 4 (24%) eventually underwent SOT. Treatment was prematurely discontinued in four patients. One of these patients underwent a kidney transplant. The overall dose compliance was 83% (169/204 scheduled doses), and 12 (71%) of 17 patients received 100% of scheduled doses. No patient developed transaminase elevations greater than twice baseline or greater than four times the upper limit of normal or clinical hepatotoxicity. No cases of TB developed during 20.4 months after transplant among INH/RPT-treated recipients.. For carefully selected SOT candidates, combination INH/RPT weekly given as directly observed therapy seems to be reasonably well tolerated and is associated with a relatively high completion rate. Future larger prospective studies to confirm the safety and high completion rates reported here and to identify the most appropriate SOT candidates for this regimen are warranted.

Topics: Adult; Aged; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Directly Observed Therapy; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Organ Transplantation; Prospective Studies; Rifampin

Topics: Child; Clinical Protocols; Contraindications; Desensitization, Immunologic; Diphenhydramine; Drug Dosage Calculations; Drug Hypersensitivity; Exanthema; Glucosephosphate Dehydrogenase Deficiency; Humans; Immune Tolerance; Isoniazid; Latent Tuberculosis; Male; Rifabutin; Rifampin

Screening and therapy of latent tuberculosis infection (LTBI) is recommended in solid organ transplant (SOT). However, there are limited data on the tolerability of LTBI therapy pretransplant and posttransplant. We studied the tolerability of LTBI therapy and effectiveness of a centralized LTBI treatment program in a low-risk population.. Provincial TB and transplant databases were retrospectively reviewed for LTBI therapy referrals in SOT candidates and recipients over a 10-year period. Using univariate logistic regression, we examined factors associated with failure to complete therapy and followed patients for active TB.. From 2001 to 2010, 200/461 SOT candidates referred to the TB program (43.4%) were eligible for therapy for LTBI. Eleven patients refused therapy. The remaining patients (n=189) were initially prescribed isoniazid (73%), rifampin (12.7%), or another regimen (14.3%). Adequate LTBI therapy occurred in 122 (64.5%). Patients who were liver transplant candidates or recipients were less likely to complete therapy than nonliver transplant patients (OR, 0.20; P<0.001) as were patients treated in the posttransplant phase (OR, 0.47; P=0.034). Liver enzyme elevation led to discontinuation of therapy more often in liver transplant candidates and recipients (OR, 10.48; P<0.001) and posttransplant treatment (OR, 3.50; P=0.019). In 599.4 patient-years of follow-up posttransplant (mean, 4.9 year/patient), there were no cases of active TB.. A centralized referral program for LTBI therapy in transplant candidates is effective to prevent TB reactivation posttransplant. A significant proportion of liver transplant candidates and recipients do not tolerate standard LTBI therapy. Alternative therapies for these patients should be evaluated.

Topics: Adult; Aged; Antitubercular Agents; Cohort Studies; Female; Follow-Up Studies; Humans; Kidney Transplantation; Latent Tuberculosis; Liver; Liver Transplantation; Male; Middle Aged; Mycobacterium tuberculosis; Organ Transplantation; Postoperative Complications; Regression Analysis; Retrospective Studies; Rifampin; Risk Factors; Transplant Recipients; Treatment Outcome; Tuberculin Test

Topics: Antitubercular Agents; Drug Costs; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Topics: Administration, Oral; Anti-Bacterial Agents; Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Latent Tuberculosis; Rifampin; Treatment Outcome

This article examines costs to treat latent tuberculosis infection (LTBI) in an urban clinic population and highlights the potential effectiveness of an alternative transitional treatment regimen.. Patients who experienced side effects on the gold standard of 9 months of isoniazid (9INH) were either continued on isoniazid or transitioned to 4 months of rifampin (4RIF). I use multilevel Tobit models with selection to analyse whether transitioning to 4RIF is less costly than remaining on 9INH among patients experiencing side effects.. Results reveal that self-selection is present in this clinic data. Using an ordered probit parametric selection rule to account for selection, I find transitioning patients to 4RIF costs significantly less than continuing on 9INH. This result is especially sensitive to selection: not controlling for selection demonstrates that patients transitioning to 4RIF actually cost significantly more to treat. Post hoc analysis revealed that switching to 4RIF significantly reduced the dropout probability among these patients.. Future work should more carefully assess the clinical attributes, including effectiveness, of treatment with 9INH and transitional 4RIF as alternative treatment for LTBI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Drug Administration Schedule; Female; Health Expenditures; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Patient Dropouts; Retrospective Studies; Rifampin; Time Factors; Urban Population; Young Adult

Children's Tuberculosis Clinic, Houston, Texas.. To describe adherence to and tolerability of 4 months of rifampicin (4RMP) compared to 9 months of isoniazid (9INH) in children with latent tuberculous infection (LTBI).. Retrospective descriptive case series of children treated for LTBI from 2010 to 2013 by self-administered therapy or directly observed preventive therapy (DOPT) administered by the local health department.. Four hundred and four children were treated, 324 (80%) with 9INH and 80 with 4RMP: the mean age was 7.3 years, and 47% were girls. Of these, 37% were identified during contact investigations. DOPT was used in 51% and self-administered therapy in 49%; 81% completed therapy. Completion of self-administered 4RMP therapy was not significantly different from completion rates for children receiving 9INH administered as DOPT (93% vs. 88%, OR 0.6, 95%CI 0.2-1.7), but was significantly higher than in the 9INH self-administration group (OR 7.9, 95%CI 2.7-23.2). Adverse events were rare: 20 (6%) in the 9INH group and 2 (3%) in the 4RMP group, and none was serious.. Completion rates for 4RMP surpassed those of 9INH for all methods of delivery, except for DOPT, where completion rates were similar. 4RMP was well tolerated. The increased cost of 4RMP over 9INH may be offset by increased effectiveness, as gauged by completion rates.

Topics: Adolescent; Age Factors; Antibiotics, Antitubercular; Chi-Square Distribution; Child; Child, Preschool; Cost-Benefit Analysis; Directly Observed Therapy; Drug Administration Schedule; Drug Costs; Female; Humans; Infant; Latent Tuberculosis; Male; Medication Adherence; Odds Ratio; Retrospective Studies; Rifampin; Texas; Time Factors; Treatment Outcome

Reactivation of latent tuberculosis infection (LTBI) is an important complication in patients treated with tumor necrosis factor-alpha (TNF-α) blocking agents. However, the best method for LTBI detection before initiation of anti-TNF therapy remains to be determined.. From January 2010 to August 2013, anti-TNF therapy was initiated in 426 patients with immune-mediated inflammatory diseases (IMIDs). Tuberculin skin test (TST) and Quantiferon-TB Gold In Tube (QFT-GIT) assay were performed before starting anti-TNF treatment. LTBI was defined as a positive TST (induration ≥ 10 mm) or as a positive QFT-GIT result. Patients were followed up until December 2013.. The positive TST and QFT-GIT rates were 22.3% (95/426) and 16.0% (68/426), respectively, yielding a total of 27.0% (115/426) of positive LTBI results. LTBI treatment was initiated in 25.1% (107/426) and was completed in 100% (107/107) of patients. During a median 294 days of follow-up, active TB occurred in 1.4% (6/426) of the patients with negative TST and QFT-GIT results at baseline.. The either test positive strategy, using both TST and QFT-GIT assay, is acceptable for LTBI screening before commencing anti-TNF therapy in patients with IMIDs.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Autoimmune Diseases; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Retrospective Studies; Rifampin; Tuberculin Test; Tumor Necrosis Factor-alpha

The bicyclic nitroimidazole-like molecule PA-824 has activity both against replicating and hypoxic non-replicating Mycobacterium tuberculosis, raising the possibility that it may have a role in the treatment of latent tuberculosis infection (LTBI). This study aimed to examine the bactericidal and sterilising activities of PA-824 against LTBI in C3HeB/FeJ mice, which develop hypoxic, necrotic granulomas histologically resembling their human counterparts. Female 5-6-week-old C3HeB/FeJ mice were immunised via the aerosol route with a recombinant BCG strain overexpressing the 30-kDa major secretory protein (rBCG30) and were aerosol-infected 6 weeks later with virulent M. tuberculosis H37Rv. Six weeks after M. tuberculosis infection, separate groups of mice were left untreated (negative controls) or were treated with either rifampicin, isoniazid (INH) or PA-824. Culture-positive relapse was assessed in subgroups of mice after 2 months and 4 months of treatment. Human-equivalent doses of PA-824 given five times weekly showed similar bactericidal activity as INH at Months 1, 2 and 4 of treatment, and 15/15 mice treated with either PA-824 or INH showed lung-culture relapse 3 months after completion of treatment. To the best of our knowledge, this is the first report examining the sterilising activity of PA-824 in an animal model of LTBI. This model may be useful for screening the efficacy of novel drugs against LTBI, particularly those with specific activity against bacilli residing within necrotic lung granulomas.

Topics: Animals; Antitubercular Agents; Disease Models, Animal; Female; Isoniazid; Latent Tuberculosis; Lung; Mice; Mice, Inbred C3H; Mycobacterium tuberculosis; Nitroimidazoles; Rifampin

Topics: Antitubercular Agents; Drug Costs; Humans; Isoniazid; Latent Tuberculosis; Rifampin

Thioridazine, a potent phenothiazine compound was evaluated for its chemotherapeutic efficacy against experiment model of tuberculosis. Thioridazine potentiated the activities of both isoniazid and rifampicin (>1 log CFU reduction) against the in vitro latent Mycobacterium tuberculosis bacilli. Further, a murine model of latent tuberculosis was used and the standard 9-month isoniazid and 4-month rifampicin regimen along with thioridazine as an adjunct drug were evaluated. Thioridazine led to an accelerated clearance of bacilli with both the regimen, thereby leading to completion of therapy much earlier than the standard end-point. In the case of 9-month isoniazid regimen, when thioridazine was used along with isoniazid as an adjunct drug, complete clearance was observed as early as 24 weeks as compared to the 36 week standard isoniazid monotherapy regimen. Also, in the 4-month rifampicin regimen, it was observed that the bacillary clearance was more robust when rifampicin was used along with thioridazine (>3 log CFU reduction) than rifampicin alone (>2 log CFU reduction). Our findings implicate that thioridazine, when used as an adjunct drug along with isoniazid or rifampicin has the potential to augment their chemotherapeutic efficacy against experimental latency.

Topics: Animals; Antitubercular Agents; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Isoniazid; Latent Tuberculosis; Male; Mice; Microbial Sensitivity Tests; Microbial Viability; Mycobacterium tuberculosis; Rifampin; Thioridazine

Topics: Antibiotics, Antitubercular; HIV Seronegativity; Humans; Latent Tuberculosis; Rifabutin; Rifampin; Tuberculosis, Pulmonary

Patients undergoing renal replacement therapy have a higher risk of developing tuberculosis (TBC) in comparison with normal renal function population. The anergy to the tuberculin skin test, the lack of characteristic clinical symptoms of TBC and typical radiographic signs, and high prevalence of extrapulmonary TBC make the diagnosis in dialysis patients difficult and often delay the treatment. In contrast to the active TBC, latent TBC infection (LTBI) is asymptomatic and is not a direct epidemiological problem. However, in patients with end-stage renal disease prepared for renal transplantation, it is an obstacle to qualifying for immunosuppressive therapy. Treatment of LTBI patients with antimycobacterial medication decreases about 90% risk of developing active TB. Therefore, the possibility of a fast and easy identification of LTBI in this group of patients is extremely important. Test QuantiFERON-TB Gold In-Tube (QFT-G) is a new, simple and rapid diagnostic tool in LTBI and active tuberculosis infection (in conjunction with previously used clinical and microbiological methods). This test has been approved and is used in many European countries and in the USA. In a 65-year old patient, treated for 5 years with continuous ambulatory peritoneal dialysis, positive QFT-G results were shownin the course of diagnosis before reporting to the transplant program. After conducting an extensive diagnosis for tuberculosis infection (epidemiological interview, clinical examination, imaging studies, cultures by MB/BacT and the conventional method, consultations with a pulmonologist), latent form of tuberculosis was diagnosed with unspecified location. Due to the positive QFT-G and the need for future immunosuppressive treatment after kidney transplantation, a three-month prophylactic treatment with Rifamazyd 450 mg per day was included. After treatment, the patient entered the waiting list for a kidney transplant. Test QFT-G, in conjunction with other conventional methods is a good and rapid diagnostic tool in the identification of LTBI.

Topics: Aged; Antitubercular Agents; Drug Administration Schedule; Female; Humans; Isoniazid; Kidney Failure, Chronic; Kidney Transplantation; Latent Tuberculosis; Peritoneal Dialysis, Continuous Ambulatory; Rifampin; Tuberculin Test

Topics: Antitubercular Agents; Emigrants and Immigrants; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin

To assess the cost-effectiveness ratio of rifampin for 4 months and isoniazid for 6 months in contacts with latent tuberculosis infection.. The cost was the sum of the cost of treatment with isoniazid for 6 months or with rifampin for 4 months of all contacts plus the cost of treatment of cases of tuberculosis not avoided. The effectiveness was the number of cases of tuberculosis avoided with isoniazid for 6 months or with rifampin for 4 months. When the cost with one schedule was found to be cheaper than the other and a greater number of tuberculosis cases were avoided, this schedule was considered dominant. The efficacy adopted was 90% for rifampin for 4 months and 69% for isoniazid for 6 months. A sensitivity analysis was made for efficacies of rifampin for 4 months of 80%, 69%, 60% and 50%.. Of the 1002 patients studied, 863 were treated with isoniazid for 6 months and 139 with rifampin for 4 months The cost-effectiveness ratio with isoniazid for 6 month was € 19759.48/avoided case of tuberculosis and € 8736.86/avoided case of tuberculosis with rifampin for 4 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies from 60%.. Rifampin for 4 months was more cost-effective than isoniazid for 6 months.

Topics: Adolescent; Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Female; Health Care Costs; Humans; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Rifampin; Sensitivity and Specificity; Spain; Treatment Outcome; Tuberculin Test; Young Adult

Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment.

Topics: Adolescent; Antibiotics, Antitubercular; Drug Interactions; Drug Monitoring; Drug Substitution; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Ketoconazole; Kidney Transplantation; Latent Tuberculosis; Liver Transplantation; Long QT Syndrome; Male; Rifabutin; Rifampin; Tacrolimus; Treatment Outcome

Treatment of latent TB infection (LTBI) in high-risk populations has been identified as a priority activity for reducing TB incidence. Treatment completion rates are usually far from the 80% target. The objective of this study was to evaluate the proportion of individuals who obtained enough medication for standard LTBI treatment.. Using the Régie de l'assurance maladie du Québec database, we extracted data on all prescriptions filled as part of the free anti-tuberculosis medication program. We calculated the proportion of patients who had obtained at least 270 doses among patients who had started treatment with isoniazid (INH), and the proportion of patients who had obtained at least 120 doses among patients who had started treatment with rifampin (RMP).. Among the 2,895 patients who had started INH, 907 (31.3%) obtained at least 270 doses. Among the 373 patients who had started RMP, 242 (64.9%) obtained at least 120 doses. Women were more likely to stop INH treatment before acquiring 270 doses of the medication than men (hazard ratio [HR] = 1.08; 95% confidence interval [CI]: 1.01-1.17).. Only 31.3% of patients who started treatment with INH had procured at least 270 doses. Completion rates are far below target values.

Topics: Adult; Aged; Antitubercular Agents; Databases, Factual; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Quebec; Rifampin; Risk Factors; Sex Factors; Young Adult

Preventive treatment may avoid future cases of tuberculosis among asylum seekers. The effectiveness of preventive treatment depends in large part on treatment completion.. In a prospective cohort study, asylum seekers of two of the Swiss Canton Vaud migration centres were screened with the Interferon Gamma Release Assay (IGRA). Those with a positive IGRA were referred for medical examination. Individuals with active or past tuberculosis were excluded. Preventive treatment was offered to all participants with positive IGRA but without active tuberculosis. The adherence was assessed during monthly follow-up.. From a population of 393 adult migrants, 98 (24.9%) had a positive IGRA. Eleven did not attend the initial medical assessment. Of the 87 examined, eight presented with pulmonary disease (five of them received a full course of antituberculous therapy), two had a history of prior tuberculosis treatment and two had contraindications to treatment. Preventive treatment was offered to 75 individuals (4 months rifampicin in 74 and 9 months isoniazid in one), of whom 60 (80%) completed the treatment.. The vulnerability and the volatility of this population make screening and observance of treatment difficult. It seems possible to obtain a high rate of completion using a short course of treatment in a closely monitored population living in stable housing conditions.

Topics: Adult; Africa; Antitubercular Agents; Asia; Balkan Peninsula; Chemoprevention; Cohort Studies; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Mass Screening; Medication Adherence; Prospective Studies; Refugees; Rifampin; Switzerland

Phenothiazines are being repurposed for treatment of tuberculosis. We examined time-kill curves of thioridazine and first-line drugs against log-growth-phase and semidormant bacilli under acidic conditions and nonreplicating persistent Mycobacterium tuberculosis. While both the potency and the efficacy of first-line drugs declined dramatically as M. tuberculosis replication rates decreased, those of thioridazine improved. The mutation prevalence to 3 times the thioridazine MIC was <1 × 10(-11), better than for ≥2 first-line drugs combined. Hollow fiber system studies revealed that the relationship between sterilizing effect and pharmacodynamic indices (PDI) was characterized by an r(2) of 0.88 for peak/MIC, an r(2) of 0.47 for the area under the concentration-time curve (AUC) to MIC, and an r(2) of 0.14 for the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) at the end of the first week. However, the PDI linked to effect "wobbled" as the duration of therapy increased, so that by the fourth week the r(2) was 0.88 for AUC/MIC, 0.78 for %TMIC, and 0.72 for peak/MIC. This "wobble" has implications on general pharmacokinetic/pharmacodynamic theory, whereby efficacy is linked to only one of the three PDIs in deterministic models. The potency changed 8.9-fold from the first to the fourth weeks. The non-protein-bound AUC/MIC associated with maximal kill at the end of therapy was 50.53 (protein binding = 99.5%). This thioridazine exposure was calculated to extinguish all three M. tuberculosis metabolic populations in human lungs in only 42.9 days of monotherapy. However, this concentration exceeds the 2- to 8-mg/liter thioridazine concentration in serum known to be lethal to humans. Therefore, the way forward for phenothiazine monotherapy that also reduces therapy duration is via synthesis of less toxic congeners.

Topics: Antipsychotic Agents; Antitubercular Agents; Colony Count, Microbial; Computer Simulation; Drug Administration Schedule; Drug Design; Drug Repositioning; Drug Resistance, Bacterial; Humans; Infusions, Intravenous; Isoniazid; Latent Tuberculosis; Microbial Sensitivity Tests; Models, Statistical; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Thioridazine; Time Factors

The case is presented of a 29-year-old woman who complained of headache over a period of several days, with loss of visual acuity and pain in her left eye. She had a 3-year history of type 1 diabetes mellitus, and was an immigrant from Ecuador. The funduscopic examination revealed a papilledema. The polymerase chain reaction (PCR) study of the cerebrospinal fluid was positive for Mycobacterium tuberculosis (MTB). She showed a marked improvement after treatment with anti-TB drugs.. About a third of the world's population has a latent infection of MTB, comorbidity between diabetes mellitus and tuberculosis has been reported, particularly in undeveloped countries.

Topics: Adult; Antitubercular Agents; Atrophy; Cerebrospinal Fluid; Developing Countries; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Ecuador; False Negative Reactions; Female; Humans; Immunocompromised Host; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Ophthalmoscopy; Optic Nerve; Papilledema; Rifampin; Spinal Puncture; Tuberculin Test; Tuberculosis, Meningeal

Topics: Antitubercular Agents; Drug Costs; Humans; Isoniazid; Latent Tuberculosis; Rifampin

A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H).. To assess the cost-effectiveness of 3HP compared to 9H.. A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H.. Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21,525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained.. 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease.

Topics: Antitubercular Agents; Computer Simulation; Cost-Benefit Analysis; Directly Observed Therapy; Drug Administration Schedule; Drug Costs; Drug Therapy, Combination; Hospital Costs; Humans; Isoniazid; Latent Tuberculosis; Models, Economic; Quality-Adjusted Life Years; Rifampin; Time Factors; Treatment Outcome; United States

Suspected latent tuberculosis infection (LTBI) is a common reason for referral to TB clinics. Interferon-gamma release assays (IGRAs) are more specific than tuberculin skin tests (TSTs) for diagnosing LTBI. The aim of this study is to determine if IGRA changes practice in the management of cases referred to a TB clinic for possible LTBI.. A prospective study was performed over 29 months. All adult patients who had TST, CXR & IGRA were included. The original decision regarding TB chemoprophylaxis was made by TB team consensus, based on clinical history and TST. Cases were then analysed with the addition of IGRA to determine if this had altered management. An independent physician subsequently reviewed the cases.. Of 204 patients studied, 68 were immunocompromised. 120 patients had positive TSTs. Of these, 36 (30%) had a positive QFT and 84 (70%) had a negative QFT. Practice changed in 78 (65%) cases with positive TST, all avoiding TB chemoprophylaxis due to QFT. Of the immunocompromised patients, 17 (25%) underwent change of practice. No cases of active TB have developed.. This study demonstrates a significant change of clinical practice due to IGRA use. Our findings support the NICE 2011 recommendations.

Topics: Adult; Antitubercular Agents; Disease Progression; Drug Therapy, Combination; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Mycobacterium tuberculosis; Practice Guidelines as Topic; Predictive Value of Tests; Prospective Studies; Referral and Consultation; Reproducibility of Results; Rifampin; Risk Assessment; Scotland; Sensitivity and Specificity; Tuberculin Test

The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was 436,842.83/50 cases avoided with rifampin for 4 months and 692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater.

Topics: Adult; Antitubercular Agents; Contact Tracing; Cost-Benefit Analysis; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Retrospective Studies; Rifampin; Spain; Tuberculosis

Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis.

Topics: Antibiotics, Antitubercular; Antibodies, Neutralizing; Bacterial Proteins; Drug Resistance, Bacterial; Gene Deletion; Gene Expression; Granuloma; Host-Pathogen Interactions; Humans; Latent Tuberculosis; Lipase; Models, Biological; Mutation; Mycobacterium tuberculosis; Rifampin; Triglycerides; Tumor Necrosis Factor-alpha

The outlook of inflammatory joint diseases has changed significantly with the advent of TNF blockers. However, these advances come with a trade off-risk of infections, especially tuberculosis. The Irish society of rheumatology has proposed guidelines to investigate and treat latent TB infection (LTBI), which is in accordance with majority of international recommendations. This protocol requires that every patient with LTBI should have chemoprophylaxis. INH and different anti-rheumatic drugs are known to cause hepatic and gastrointestinal complications. We sought to investigate the toxicity of adding prophylactic anti-TB medications to different DMARDs and anti-TNF agents. We prospectively documented the course of all patients who were prescribed chemoprophylaxis for LTBI, from August 2007 to August 2008. Arrangements were made for central re-issuing of prescription of INH or rifampicin, after reviewing monthly liver function tests and following telephone interview seeking presence of adverse events. Out of 132 patients who were commenced on different TNF blockers, only 23 patients (17%) were diagnosed with LTBI and were given prophylaxis as per recommended guidelines. Thirty-nine percent (9 out of 23) of patients discontinued INH because of adverse events. Primary reason for discontinuation in these 9 patients was as follows: 3 patients got marked transaminitis (transaminases >5 times the normal limit), 5 patients had non-resolving gastrointestinal intolerance (mainly nausea), and one patient developed non-resolving rash. We have found a significant number of our patients (39%) who could not continue anti-TB prophylaxis due to either gastrointestinal intolerance or hypertransaminesemia.

Topics: Adult; Aged; Antirheumatic Agents; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Chemoprevention; Female; Gastrointestinal Diseases; Humans; Incidence; Isoniazid; Latent Tuberculosis; Liver Function Tests; Male; Middle Aged; Mycobacterium tuberculosis; Prospective Studies; Retrospective Studies; Rheumatic Diseases; Rifampin; Risk Factors; Tumor Necrosis Factor-alpha

We screened tuberculosis (TB) contacts as an outbreak investigation with tuberculin skin test (TST) and interferon-gamma release assay (IGRA). We evaluated adverse events and TB incidence in all persons screened after rifampicin (RFP) prophylaxis, and specifically assessed the new TB cases in relation to initial TST and IGRA results. The 180 contacts were divided into four groups: TST+/IGRA+ (n = 101), TST+/IGRA- (n = 22), TST-/IGRA+ (n = 16), and TST-/IGRA- (n = 41). RFP treatment (4 months) was prescribed only to the TST+/IGRA+ group. Of 87 contacts who initiated prophylaxis, adverse events occurred in 21 contacts (24.1%) including hepatotoxicity (11.5%), flu-like syndrome (5.7%), and thrombocytopenia (3.4%). TB developed in two TST+/IGRA+ subjects after completion of prophylaxis, including one multidrug-resistant (MDR)-TB case during 21.8 months of follow-up. Adverse events were frequent, and development of TB including MDR-TB occurred after RFP prophylaxis.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Disease Outbreaks; Female; Group Homes; Humans; Latent Tuberculosis; Male; Middle Aged; Republic of Korea; Rifampin; Tuberculosis, Pulmonary; Young Adult

Few data are available on the impact of a tuberculosis exposure on newborns in a maternity ward.. To describe the screening and clinical course of infants exposed during the neonatal period to a caregiver with bacillary tuberculosis.. Infants exposed during the postnatal period in a maternity unit in Paris, from March to August 2005, to a caregiver with bacillary tuberculosis were included in a standardized screening protocol. The screening performed at baseline (M0) and at 3 months (M3) included a clinical evaluation, a tuberculin skin test (TST), and a chest X-ray. A preventive treatment for tuberculosis with isoniazid and rifampicin for 3 months was systematically proposed.. At M0, 182 of the 217 infants (84%) with significant exposure were evaluated. Data were available for 172 infants. The median age at M0 was 4.9 months (IQR=3.8-6.2). At M0, 4 of 172 infants (2.3%) had latent TB infection. Between M0 and M3, 19 infants (11%) were lost to follow-up and 1 on 153 developed a latent TB infection. No cases of tuberculosis disease were diagnosed. The treatment was administered properly in 83% of cases and side effects were observed in 11% of infants without any serious adverse event. Four infants received no treatment and 11 stopped their treatment prematurely.. In the absence of neonatal massive exposure, although low (2.9%), the risk of latent TB infection requires close monitoring of the infants exposed. However, in the context of a mild exposure in the maternity unit, surveillance without systematic initiation of TB preventive treatment could be discussed.

Topics: Antitubercular Agents; Cohort Studies; Cross Infection; Female; Follow-Up Studies; Humans; Infant; Infectious Disease Transmission, Professional-to-Patient; Isoniazid; Latent Tuberculosis; Male; Mass Chest X-Ray; Mass Screening; Obstetrics and Gynecology Department, Hospital; Paris; Rifampin; Risk Factors; Tuberculin Test; Tuberculosis, Pulmonary

Tuberculosis contact investigation identifies individuals who may be recently infected with tuberculosis and are thus at increased risk for disease. Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis to prevent active disease; however, the effectiveness of this intervention is unclear as treatment completion is generally low.. A retrospective cohort study of 30 561 contacts identified during investigation of 5182 cases of tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched the NYC tuberculosis registry to identify contacts developing active tuberculosis within 4 years of follow-up. We estimated the following: number of contacts undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per prevalent case diagnosed; number of contacts with LTBI that need to be treated with standard chemoprophylaxis to prevent 1 active case.. Of 30 561 contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102 contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90-115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who did not complete treatment. During 4 years of follow-up, active tuberculosis was diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI, .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis case (95% CI, 53-164).. Contact investigation facilitates active case finding and tuberculosis prevention, even when completion rates of chemoprophylaxis are suboptimal.

Topics: Adolescent; Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Child; Child, Preschool; Cohort Studies; Contact Tracing; Female; Follow-Up Studies; Humans; Infant; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; New York City; Numbers Needed To Treat; Prevalence; Retrospective Studies; Rifampin; Tuberculin Test; Tuberculosis; Young Adult

Topics: Adult; Antitubercular Agents; Cohort Studies; Disease Progression; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Patient Compliance; Portugal; Pyrazinamide; Retrospective Studies; Rifampin

Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-starved 18b (SS18b) model both in vitro and in vivo by comparing the behavior of 22 approved and experimental tuberculosis drugs. Using the resazurin reduction microplate assay (REMA), rifampin (RIF), rifapentine (RPT), TMC207, clofazimine (CFM), and linezolid (LIN) were found to be active against SS18b in vitro, and their bactericidal activity was confirmed by determining the number of CFU. A latent 18b infection was established in mice, and some of the above-mentioned drugs were used for treatment, either alone or in combination with RIF. RIF, RPT, TMC207, CFM, and pyrazinamide (PZA) were all active in vivo, while cell wall inhibitors were not. A comparative kinetic study of rifamycin efficacy was then undertaken, and the results indicated that RPT clears latent 18b infection in mice faster than RIF. Intrigued by the opposing responses of live and dormant 18b cells to cell wall inhibitors, we conducted a systematic analysis of 14 such inhibitors using REMA. This uncovered an SS18b signature (CWPRED) that accurately predicted the activities of cell wall inhibitors and performed well in a blind study. CWPRED will be useful for establishing the mode of action of compounds with unknown targets, while the SS18b system should facilitate the discovery of drugs for treating latent tuberculosis.

Topics: Acetamides; Amino Acid Sequence; Animals; Antitubercular Agents; Clofazimine; Diarylquinolines; Disease Models, Animal; Drug Discovery; Drugs, Investigational; Female; Genetic Engineering; Latent Tuberculosis; Linezolid; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Sequence Data; Mycobacterium tuberculosis; Oxazines; Oxazolidinones; Quinolines; Rifampin; Streptomycin; Structure-Activity Relationship; Xanthenes

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.

Topics: Antitubercular Agents; Epidemiological Monitoring; Ethambutol; Greece; Humans; Isoniazid; Latent Tuberculosis; Prescription Drugs; Pyrazinamide; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

Guidelines recommend treatment of latent tuberculosis in patients at increased risk for active tuberculosis. Studies investigating the association of therapy with serious adverse events have not included the entire treated population nor accounted for comorbidities or occurrence of similar events in the untreated general population. Our objective was to estimate the risk of adverse events requiring hospital admission that were associated with therapy for latent tuberculosis infection in the general population.. Using administrative health data from the province of Quebec, we created a historical cohort of all residents dispensed therapy for latent tuberculosis between 1998 and 2003. Each patient was matched on age, sex and postal region with two untreated residents. The observation period was 18 months (from 6 months before to 12 months after initiation of therapy). The primary outcome was hospital admission for therapy-associated adverse events.. During the period of observation, therapy for latent tuberculosis was dispensed to 9145 residents, of whom 95% started isoniazid and 5% started rifampin. Pretreatment comorbid illness was significantly more common among patients receiving such therapy compared with the matched untreated cohort. Of all patients dispensed therapy, 45 (0.5%) were admitted to hospital for a hepatic event compared with 15 (0.1%) of the untreated patients. For people over age 65 years, the odds of hospital admission for a hepatic event among patients treated for latent tuberculosis infection was significantly greater than among matched untreated people after adjustment for comorbidities (odds ratio [OR] 6.4, 95% CI 2.2-18.3). Excluding patients with comorbid illness, there were two excess admissions to hospital for hepatic events per 100 patients initiating therapy compared with the rate among untreated people over 65 years (95% CI 0.1-3.87).. The risk of adverse events requiring hospital admission increased significantly among patients over 65 years receiving treatment for latent tuberculosis infection. The decision to treat latent tuberculosis infection in elderly patients should be made after careful consideration of risks and benefits.

Topics: Adult; Age Distribution; Aged; Antitubercular Agents; Case-Control Studies; Chemical and Drug Induced Liver Injury; Comorbidity; Female; Humans; Isoniazid; Latent Tuberculosis; Logistic Models; Male; Middle Aged; Patient Admission; Quebec; Retrospective Studies; Rifampin; Risk Assessment

Topics: Age Factors; Asymptomatic Infections; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Patient Compliance; Rifampin; Risk Factors; Self Administration

Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is an emerging global health threat. Proper management of close contacts of infectious patients is increasingly important. However, no evidence-based recommendations for treating latent TB infection (LTBI) after MDR/XDR-TB exposure (DR-LTBI) exist. An ultrashort regimen for LTBI caused by drug-susceptible strains (DS-LTBI) is also desirable. TMC207 has bactericidal and sterilizing activity in animal models of TB and improves the activity of current MDR-TB therapy in patients.. The objective of this study was to determine whether TMC207 might enable short-course treatment of DR-LTBI and ultrashort treatment of DS-LTBI.. Using an established experimental model of LTBI chemotherapy in which mice are aerosol-immunized with a recombinant bacillus Calmette-Guérin vaccine before low-dose aerosol infection with Mycobacterium tuberculosis, the efficacy of TMC207 alone and in combination with rifapentine was compared with currently recommended control regimens as well as once-weekly rifapentine + isoniazid and daily rifapentine ± isoniazid.. Outcomes included monthly lung colony-forming unit counts and relapse rates.. Lung colony-forming unit counts were stable at about 3.75 log(10) for up to 7.5 months postinfection in untreated mice. Rifamycin-containing regimens were superior to isoniazid monotherapy. TMC207 exhibited sterilizing activity at least as strong as that of rifampin alone and similar to that of rifampin + isoniazid, but daily rifapentine +/- isoniazid was superior to TMC207. Addition of TMC207 to rifapentine did not improve the sterilizing activity of rifapentine in this model.. TMC207 has substantial sterilizing activity and may enable treatment of DR-LTBI in 3-4 months.

Topics: Animals; Antibiotics, Antitubercular; Antitubercular Agents; Diarylquinolines; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Female; Latent Tuberculosis; Lung; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Quinolines; Rifampin; Stem Cells; Treatment Outcome

Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability.. To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI).. We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms.. Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen.. Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.

Topics: Antitubercular Agents; Cost-Benefit Analysis; Drug Administration Schedule; Humans; Isoniazid; Latent Tuberculosis; Models, Biological; Patient Compliance; Rifampin; Self Administration; United States

To compare rates of treatment interruption because of side effects and completion rates between subjects treated for latent tuberculosis infection (LTBI) by isoniazid (INH) for 6 months and subjects treated with rifampicin (RIF) for 4 months.. Retrospective analysis of all patients treated for LTBI by INH (1993-2002) or RIF (2004-2007) based on a database including age, gender, prior liver diseases, alcohol consumption, completion rates, time and cause of interruption and monthly analysis of ASAT and ALAT.. 624 subjects were included, 426 treated by INH and 198 by RIF. Gender, origin, history of prior hepatic disease and alcohol excess did not differ between groups. Treatment interruption because of hepatotoxicity was significantly higher in the INH group than in the RIF group (6.1% vs 2.0%; p = 0.03). Completion of treatment was significantly higher in the RIF group compared to the INH group (83% vs 74%; p = 0.02).. A 4-month RIF treatment was associated with significantly less interruption of treatment because of hepatotoxicity and higher completion rates compared to a 6-month INH regimen. These results support the RIF regimen as an alternative to the presently recommended 9 months of INH in clinical practice.

Topics: Adult; Alanine Transaminase; Antitubercular Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Middle Aged; Retrospective Studies; Rifampin; Young Adult

Topics: Adolescent; Antitubercular Agents; Child; Drug Administration Schedule; Drug Dosage Calculations; Humans; Isoniazid; Latent Tuberculosis; Mycobacterium tuberculosis; Patient Compliance; Rifampin; United States

A 75-year-female with a history of Isoniazid (INH) therapy for latent tuberculosis, was admitted with a 4-week duration of dyspnea, cough, and pleuritic chest pain. She was treated with intravenous antibiotics for a diagnosis of pneumonia. Her stay was complicated by development of recurrent, exudative eosinophilic pleural effusions (EPEs). When symptoms continued to worsen and she developed joint pain and anasarca and did not respond to the antibiotics, a rheumatologic work-up was performed. She was found to have positive anti-double stranded-DNA antibodies and anti-histone antibodies; thus, a diagnosis of drug-induced lupus, secondary to INH, was made. INH was discontinued, and the patient was started on prednisone; within weeks her symptoms resolved. This case illustrates a unique side effect of INH that caused exudative EPEs and drug-induced lupus with positive anti-dsDNA.

Topics: Aged; Antibodies, Antinuclear; Antitubercular Agents; DNA; Drug Substitution; Eosinophilia; Exudates and Transudates; Female; Glucocorticoids; Humans; Isoniazid; Latent Tuberculosis; Lupus Erythematosus, Systemic; Pleural Effusion; Prednisone; Rifampin; Treatment Outcome

Preventing tuberculosis (TB) by treating latent Mycobacterium tuberculosis infection (LTBI) is a cornerstone of the U.S. strategy for TB elimination. Three randomized controlled trials have shown that a new combination regimen of isoniazid (INH) and rifapentine (RPT) administered weekly for 12 weeks as directly observed therapy (DOT) is as effective for preventing TB as other regimens and is more likely to be completed than the U.S. standard regimen of 9 months of INH daily without DOT. This report provides CDC recommendations for using the INH-RPT regimen. The new regimen is recommended as an equal alternative to the 9-month INH regimen for otherwise healthy patients aged≥12 years who have LTBI and factors that are predictive of TB developing (e.g., recent exposure to contagious TB). The new regimen also can be considered for other categories of patients when it offers practical advantages. Although the INH-RPT regimen was well tolerated in treatment trials, monitoring for adverse effects is recommended. Severe adverse effects should be reported to the Food and Drug Administration (FDA) and CDC.

Topics: Adult; Antitubercular Agents; Child; Child, Preschool; Contraindications; Directly Observed Therapy; Drug Administration Schedule; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifampin

Low adherence to treatment of latent tuberculosis infection (TLTBI) diminishes TB prevention efforts. This study examined the treatment completion rate among those who started TLTBI and factors associated with adherence to TLTBI.. Patients who started TLTBI in New York City (NYC) Health Department chest clinics during January 2002-August 2004 were studied. TLTBI completion rate were described and compared according to patient demographic and clinical characteristics by regimen using univariate analysis and log-binomial regression.. A total of 15 035 patients started and 6788 (45.2%) completed TLTBI. Treatment completers were more likely than non-completers to be >or=35 years old (52.5%, adjusted relative risk (aRR)=1.2, 95% confidence interval (CI)=1.1, 1.2), contacts to pulmonary TB patients (57.4%, aRR=1.5, 95% CI=1.4, 1.7), treated by directly observed preventive therapy (DOPT) (71.4%, aRR=1.3, 95% CI=1.2, 1.3), and to have received the rifamycin-based regimen (60.0%, aRR=1.2, 95% CI=1.1, 1.3). The completion rate with an isoniazid regimen did not differ between HIV-infected and HIV-uninfected persons. Among those who failed to complete, 3748 (47.8%) failed to return for isoniazid and 59 (14.7%) for rifamycin after the first month of medication dispensing.. Shorter regimen and DOPT increased completion rates for LTBI. Though efforts to improve TLTBI completion need to address all groups, greater focus is needed for persons who are contacts and HIV-infected, as they have higher risk of developing TB.

Topics: Adolescent; Adult; Antitubercular Agents; Cohort Studies; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Mycobacterium tuberculosis; New York City; Regression Analysis; Retrospective Studies; Rifampin; Young Adult

Even though some studies have reported the results of serial interferon-gamma release assays (IGRAs) during isoniazid prophylactic treatment, serial results have not been reported after rifampicin prophylaxis. A contact investigation was conducted after a tuberculosis (TB) outbreak in an accommodation facility. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed in 214 contacts with normal chest radiographs. Rifampicin prophylaxis was initiated in TST+/QFT-GIT+ subjects, and the QFT-GIT test was repeated upon completion of 4 months of rifampicin treatment. Among the 214 contacts, the TST and QFT-GIT test results were positive in 67.7% and 56.7%, respectively, and the agreement between the two tests was fair-to-good (78.3%, kappa=0.55, p<0.001). The QFT-GIT test was positive in 77% (97/126) of contacts with positive TST results. Rifampicin prophylaxis was completed in 81 subjects with good compliance. Among 74 subjects with valid serial QFT-GIT test results, IFN-gamma levels decreased in 97.3% (72/74) of the subjects and QFT-GIT test reversion (positive to negative) was achieved in 31 subjects (41.9%). Subjects without QFT-GIT test reversion had a significantly higher baseline TST induration sizes (18.3+/-4.8 vs. 14.9+/-3.4mm, p<0.01) and IFN-gamma levels (18.6+/-17.9 vs. 3.2+/-7.5IU/mL, p<0.01) than the subjects with QFT-GIT test reversion. Thus, IGRAs may be useful in evaluating the therapeutic response to rifampicin prophylaxis in TB contacts. However, considering that this was not a controlled study, a prospective controlled study is needed to determine whether rifampicin prophylaxis truly affects QFT-GIT reversion.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Disease Outbreaks; Female; Humans; Interferon-gamma; Latent Tuberculosis; Male; Middle Aged; Republic of Korea; Rifampin; Tuberculin Test; Tuberculosis, Pulmonary; Young Adult

Interferon-gamma (IFN-gamma) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.. 481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.. The QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST > or = 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-gamma responses were comparable at start (mean 6.13 IU/ml +/- SD 3.99) and after three months (mean 5.65 IU/ml +/- SD 3.66) and 15 months (mean 5.65 IU/ml +/- SD 4.14), (p > 0.05).. Only one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Animals; Antitubercular Agents; Child; Clinical Laboratory Techniques; Drug Monitoring; Female; Follow-Up Studies; Humans; Immunoassay; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Mycobacterium tuberculosis; Radiography, Thoracic; Rifampin; Risk Factors; Sputum; Surveys and Questionnaires; Young Adult

Aerobic (5-day-old cultures) and nonreplicating (dormant) Mycobacterium tuberculosis (5-, 12-, and 19-day-old cultures) bacteria were treated with rifampin (R), moxifloxacin (MX), metronidazole (MZ), amikacin (AK), or capreomycin (CP) for 7, 14, and 21 days. R-MX-MZ-AK and R-MX-MZ-CP killed both aerobic and dormant bacilli in 21 days, as shown by lack of regrowth in solid and liquid media. R-MX-MZ-AK and R-MX-MZ-CP also caused a strong decrease of nonreplicating bacilli in 7 days in a cell-based dormancy model.

Topics: 3T3 Cells; Adipocytes; Amikacin; Animals; Antitubercular Agents; Aza Compounds; Capreomycin; Colony Count, Microbial; Drug Combinations; Drug Resistance, Bacterial; Fluoroquinolones; Humans; In Vitro Techniques; Latent Tuberculosis; Metronidazole; Mice; Microbial Sensitivity Tests; Models, Biological; Moxifloxacin; Mycobacterium tuberculosis; Quinolines; Rifampin

BACKGROUND/SETTING: Treatment for 3 months with rifampicin (R) and isoniazid (H) (3RH) for latent tuberculosis infection (LTBI), defined as an inappropriately positive tuberculin skin test with no clinical or x-ray evidence of disease, has been used locally since 1989. The efficacy of this regimen in children in the UK has only been studied indirectly. The long-term outcome of those children treated with 3RH, in the Chest Clinic of this high tuberculosis (TB) incidence district, has been studied to derive a more direct assessment of effectiveness.. All children treated with 3RH for LTBI from 1989 to 2004 inclusive were matched with the local patient administration system (PAS), GP registration and local TB notification databases. Only those persons still registered locally on PAS, or locally GP registered were then checked for subsequent TB notification.. A total of 334 patients were identified, of whom 252 remained locally, with 82 lost to follow-up; 3 cases of clinical TB developed in the 252 (1.19%), with 3113 years observation (mean 12.35 years) giving 0.964/1000 person years (95% CI 0.199 to 2.816). Sensitivity analyses showed a 'best case' scenario of 0.727/1000 person years (95% CI 0.15 to 2.12), and if 10% of those lost to follow-up developed clinical TB of 2.66/1000 person years (95% CI 1.33 to 4.77).. Follow-up of those cases treated with 3RH, for a mean of 12.35 years, and over 3100 patient years observation, shows a rate of active TB of under 1/1000 patient years. This suggests that 3RH has very high efficacy when used to treat LTBI in children in the UK and compares favourably with the expected untreated TB rate.

Topics: Adolescent; Antitubercular Agents; Child; Drug Administration Schedule; Drug Therapy, Combination; England; Follow-Up Studies; Humans; Infant; Isoniazid; Latent Tuberculosis; Rifampin; Treatment Outcome; Tuberculosis

Topics: Antibiotics, Antitubercular; Health Care Costs; Humans; Latent Tuberculosis; Rifampin

Isoniazid (I) is the drug of choice for treating latent tuberculous infection (LTI). Duration of treatment with I and its liver toxicity represent a serious drawback for a correct enforceability. In several clinical guides, a 3-month course with rifampicin (Rif) and I is recommended as an acceptable alternative to the 6-9 month course with I. Here we present our experience with this new regimen.. From 2001, the 3-month regimen with Rif and I was offered to patients older than 14 years, who were recruited in the contacts study. A good adherence was considered when the patient manifested so and he/she went to the scheduled monthly controls. We performed baseline liver analyses in those patients at risk of hepatotoxicity and in all patients older than 35 years. In all cases, a liver laboratory control was done at the first month of treatment and whenever patients had symptoms suggestive of intolerance. Databases of tuberculosis controls and contacts were crossed to evaluate the number of individuals who developed tuberculosis.. Between 2000 and 2008, treatment for LTI was indicated in 547 contacts (7.8% refused treatment, 34.1% with the 6-month I course, 63.5% with the 3-month Rif and I course and 2.3% with other regimens). A total of 84.97% (147/173) patients with the 6-month I regimen and 92.55% (302/322) with the 3-month Rif and I course fulfilled the treatment (p=0.024). 2.37% (4/169) and 1.6% (5/313) patients with the 6-month I course and 3-month Rif and I course, respectively, withdrew because of hepatotoxicity (p=0.33). There were no patients among those who fulfilled the treatment in any of the 2 study arms.. There was a higher adherence (statistically significant) and lower hepatotoxicity with the 3-month Rif and I regimen. Both regimens showed a full effectivity.

Topics: Adolescent; Adult; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Medication Adherence; Prospective Studies; Rifampin; Time Factors; Young Adult