
PK of Levofloxacin in MDR-TB Patients
Multi-drug Resistant TuberculosisThe emergence and spread of multi-drug resistant and extensively-drug resistant strains of Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various factors contributing to the development of drug resistance, low drug exposure is well recognized. To overcome this, either new drugs have to be developed or the dose of currently used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired drug resistance to these drugs could complicate and narrow down the available options, and further exacerbate to pre-XDR and XDR-TB. Objective: The main objective of this prospective clinical study is to understand the pharmacokinetics of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body weight and correlate drug exposure, with treatment outcomes. Study design: A prospective pharmacokinetic study Study population: 20 MDR-TB patients Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on the body weight, under MDR-TB treatment regimen of Nepal. Main study parameters/end points: The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated in plasma and in oral fluid

Evaluation of PCR Using DNA Extract From Slides and Filter Paper for the Detection of Tuberculosis...
TuberculosisMulti Drug Resistant TuberculosisSpecimen transport from peripheral health structures to the National TB reference laboratory for MDR-TB identification presents a big challenge in term of sample management, safety, contamination and delays. Thus a system that allows specimen to be collected and shipped in a safely manner while reducing the possibilities of contamination, the cost of shipment and especially the time for detection of MDR-TB by using molecular methods would be very useful. Whereas the some studies show promising results for the development and standardization of simple specimen collection and transportation methods for molecular DST, more data is needed before these can be used in routine. The study described here aims at identifying a suitable method, in terms of adapted sample support (s) (slide, filter paper (FTA, Genocard ...)) and DNA extraction method. If one or several methods are found to give satisfying results, then a larger patient based evaluation of this (these) method(s) for molecular DST will be performed in a second phase. The protocol for the second phase will be prepared separately.

Pharmacokinetic Study of Patients Who Undergo Cycloserine, a 2nd-line Antituberculosis Medicament...
Pulmonary TuberculosisIn all treatments of tuberculosis, the second-line drugs are usually less effective but have more drug toxicity than the first-line ones. For the multidrug-resistant tuberculosis (MDR-TB) patients, who are resistant to the major first-line anti-tuberculosis drugs such as Rifampin and Isoniazid, the second-line agents, like Cycloserine in this research, are in frequent use. Taking patients' safety into consideration, therapeutic drug monitoring of Cycloserine has been listed as a routine examination during the tuberculosis treatment and established a suggested Cycloserine serum concentration of 20~35 mcg/mL. While this suggested drug concentration was set up, it isn't suitable to all races in the world. The investigators plan to develop the therapeutic drug monitoring protocols and a suggested treating concentration fitting for Asian (Taiwanese). In addition, through this research, the investigators can also realize that factors causing different pharmacokinetics and the clinical outcomes in different Cycloserine level.

Enhanced Tuberculosis Case Detection Among Substitution Treatment Patients
TuberculosisThe purpose of this study was to determine the prevalence of latent tuberculosis infection among injecting drug users and to conduct randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among injecting drug users referred from a methadone drug treatment program in Estonia.

Comparing Two Preventive Regimens for Latent Tuberculosis Infection (LTBI)
Latent Tuberculosis InfectionThough still an endemic area, the incidence of tuberculosis (TB) in Taiwan is decreasing in recent years. Further reduction in TB incidence, or even elimination should rely on treatment for LTBI. However, which is the cost-effective screening method or what is the cost-effective regimen in Taiwan is still unclear. Therefore, the investigators designed this prospective study to follow up adult household contacts with LTBI for 2 years and compare the efficacy of 9-month isoniazid and 4-month rifampicin).

Effect of Weight and/or Obesity on Ethambutol Drug Concentrations
ObesityTuberculosisThis study is designed to measure drug concentrations in the blood of healthy volunteers administered a single dose of ethambutol. Our hypothesis is that volunteers with a body mass index (BMI) 25-40 kg/m2 will remove ethambutol more quickly from the blood than leaner volunteers, and those with a BMI > 40 kg/m2 will have even greater clearance than those who are leaner.

Intravitreal Bevacizumab in Recalcitrant Inflammatory Ocular Neovascularization
NeovascularizationTuberculosis2 moreOne complication of uveitis which is driven by an increase in VEGF is the formation of inflammatory ocular neovascularization (ION). Here, we analyze the therapeutic role of intravitreal bevacizumab in ION not responding to standard therapy (systemic and ocular corticosteroids and systemic immunosuppressants) in a multicenter retrospective study.The natural history of subfoveal choroidal new vessels histoplasmosis, multifocal choroiditis, Harada and other inflammatory chorioretinal disorders has been very guarded, but with this new approach, we hope to stop the visual loss in these relatively young patients.

Deworming Against Tuberculosis
TuberculosisThe purpose of this study is to investigate whether treatment against intestinal helminths in patients with pulmonary tuberculosis undergoing chemotherapy could improve the clinical outcome by enhancing host immunity.

Sputum Pharmacokinetics of TB Drugs and Bacterial Drug Resistance
TuberculosisNon-Tuberculosis MycobacteriaBackground: Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. They will look at how much medicine is in your sputum (what you cough up) compared to how much is in your blood. They will also investigate a new test to quickly figure out what medicines are likely to treat TB effectively. Objective: To determine the relationship between the concentration of TB drugs in plasma and sputum over time. Eligibility: People ages 18 and older who have TB or NTM infection that is suspected to be drug resistant. They must be taking TB or NTM medicines. Design: Participants will be screened with medical history. Participants will be in the study for 2 8 days. Participants will give 3 or more sputum samples over at least 2 different days. They will cough sputum into a cup. Participants will have blood drawn 4 times a day on 2 different days.

Clinical Decision-support Reminders to Improve IPT Initiation Among HIV Positive Adults in Western...
TuberculosisThe overall research objective is to evaluate the impact of implementing a reminder system for medical providers to improve TB case-finding and isoniazid preventative therapy (IPT) for adults living with HIV in western Kenya