NEWS HIGHLIGHTSMedia Articles Related to Pyrazinamide
World Lung Foundation Warns U.S. Budget Cuts Will Slow The Fight Against Multi-Drug Resistant Tuberculosis
Source: Health News from Medical News Today [2013.05.24]
World Lung Foundation (WLF) today warned that the sequestration of the United States Federal Budget will have the unintended consequence of slowing efforts to control and eradicate tuberculosis - particularly multi-drug resistant tuberculosis - both in the U.S. and around the world. Under the sequestration, the budget of the Tuberculosis Trials Consortium (TBTC), one of the premier TB clinical research groups in the world, will immediately be reduced by 25-30 percent, with a similar cut in the next financial year...
'Alarming' Rise Seen in Drug-Resistant Tuberculosis
Source: MedicineNet Tuberculosis Specialty [2012.08.31]
Title: 'Alarming' Rise Seen in Drug-Resistant Tuberculosis
Category: Health News
Created: 8/30/2012 2:05:00 PM
Last Editorial Review: 8/31/2012 12:00:00 AM
Tuberculosis
Source: MedicineNet Neutropenia Specialty [2011.07.22]
Title: Tuberculosis
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 7/22/2011 12:00:00 AM
Drug-Resistant TB Destroyed By Vitamin C
Source: MRSA / Drug Resistance News From Medical News Today [2013.05.24]
In a striking, unexpected discovery, researchers at Albert Einstein College of Medicine of Yeshiva University have determined that vitamin C kills drug-resistant tuberculosis (TB) bacteria in laboratory culture. The finding suggests that vitamin C added to existing TB drugs could shorten TB therapy, and it highlights a new area for drug design...
Consensus Statement On Research Definitions For Drug-Resistant TB In Children
Source: Infectious Diseases / Bacteria / Viruses News From Medical News Today [2013.05.23]
The Journal of the Pediatric Infectious Diseases Society (JPIDS) has released its June issue, which includes a consensus statement of the global Sentinel Project on Pediatric Drug-Resistant Tuberculosis. It establishes standardized definitions, measurements, and other key attributes that will affect research...
Published Studies Related to Pyrazinamide
14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and
moxifloxacin combinations: a randomised trial. [2012]
first 14 days of treatment to assess their suitability for future development... INTERPRETATION: PA-824-moxifloxacin-pyrazinamide is potentially suitable for
Pyrazinamide blood concentrations in children suffering from tuberculosis: a comparative study at two doses. [2008.03]
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Pyrazinamide is recommended in doses varying from 15 to 40 mg kg(-1). The most commonly used average daily dose is 25 mg kg(-1). Its use is associated with dose dependent hepatotoxicity. Lower doses are not used because of lack of pharmacokinetic data especially in children. There is only one detailed study of pyrazinamide in children at a dose of 35 mg kg(-1). WHAT THIS STUDY ADDS: This is the first study evaluating serum concentrations of pyrazinamide in children at a dose of 15 mg kg(-1) which is on the lower side of the recommended dose. The study also compared the serum concentrations and pharmacokinetics achieved with this dose with the widely used dose of 25 mg kg(-1) in children suffering from tuberculosis. The pharmacokinetics and pharmacodynamic indices of pyrazinamide were comparable with the 25 and 15 mg kg(-1) doses. AIMS: To evaluate the pharmacokinetics and pharmacodynamic indices of pyrazinamide at doses of 15 and 25 mg kg(-1) in children suffering from tuberculosis... CONCLUSIONS: The study indicates that comparable serum concentrations of pyrazinamide are attained with 25 mg kg(-1) and 15 mg kg(-1) doses in children. The elimination half-life was longer and volume of distribution greater in children than in the adult population.
Biological evaluation of pyrazinamide liposomes for treatment of Mycobacterium tuberculosis. [2007.02.07]
Pyrazinamide liposomes were prepared employing the phospholipid molar ratios; dipalmitoyl phosphatidyl choline (7):cholesterol (2) neutral and dipalmitoyl phosphatidyl choline (7):cholesterol (2):dicetyl phosphate (1) negatively charged. Swelling at 52 degrees C led to higher trapping efficiencies...
Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. [2006.04.15]
RATIONALE: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. OBJECTIVES: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil... CONCLUSIONS: Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus? [2005.03]
SETTING: Nine public health care centres in four Spanish cities. OBJECTIVE: To evaluate the efficacy and safety of 2 months of rifampicin (R) plus pyrazinamide (Z) therapy (2RZ) compared with a 6-month course of isoniazid therapy (6H) for treating latent tuberculosis infection (LTBI).We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible.
Clinical Trials Related to Pyrazinamide
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) [Recruiting]
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral
administration of TMC207 plus PA-824 plus Pyrazinamide plus Clofazimine, TMC207 plus PA-824
plus Pyrazinamide, TMC207 plus PA-824 plus Clofazimine alone, TMC207 plus Pyrazinamide plus
Clofazimine, Pyrazinamide alone, Clofazimine alone, and standard first line TB treatment as
per South African TB Guidelines (Rifafour e-275) as determined by the rate of change of log
CFU per ml sputum over the time period Day 0-14 in participants with smear positive
pulmonary tuberculosis (TB). A control group will receive standard treatment.
Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis [Recruiting]
REMoxTB is a study for the "Rapid Evaluation of Moxifloxacin in the treatment of sputum
smear positive tuberculosis". REMoxTB aims to find and evaluate new drugs and regimens that
shorten the duration of tuberculosis therapy.
The purpose of REMoxTB is to evaluate the efficacy, safety and acceptability of two
moxifloxacin-containing treatment combinations to determine whether substituting ethambutol
with moxifloxacin in one combination, and/or substituting isoniazid with moxifloxacin in
another combination, makes it possible to reduce the duration of treatment for TB.
Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis [Recruiting]
Although effective therapy for tuberculosis is available, TB continues to cause significant
problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A
major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and
complicated treatment regimens. Incomplete TB treatment can lead to serious consequences
such as increased severity of illness and death, prolonged infectiousness and transmission
in the community, and the development of drug resistance. The development of new treatment
strategies with more stronger drugs could lead to shorter and simpler regimens. A TB
treatment regimen that allowed treatment duration to be meaningfully decreased would have
important public health implications.
This trial will compare the effect and safety of a new oral regimen to that of the standard
regimen for the first phase of treatment for pulmonary tuberculosis.
The experimental regimen will consist of the following:
- Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered
once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
The standard control intensive phase regimen will consist of the following:
- Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered
once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Following intensive phase therapy (the study phase), all patients will be treated with a
non-experimental continuation phase regimen.
In mice, the combination of Moxifloxacin and Rifapentine have cured the animals
significantly faster than the standard regimen and this study will be the first step to see
if the potential is also there in humans.
Safety, Tolerability, Extended Early Bactericidal Activity and PK of Higher Doses Rifampicin in Adults With Pulmonary TB [Recruiting]
This is the first trial in a series of clinical trials that aim to bring the concept of high
dose rifampicin beyond phase II of clinical development.
The safety, tolerability, extended early bactericidal activity (EBA) and pharmacokinetics of
several doses of Rifampicin with or without standard doses of Isoniazid, Pyrazinamide and
Ethambutol in adults with newly diagnosed, uncomplicated, smear positive, pulmonary TB will
be assessed. The objective of this study is to find the maximum tolerable dose of Rifampicin
as monotherapy and in combination with the currently available Isoniazid, Pyrazinamide and
Ethambutol.
The subjects will be in the study for 24-31 days. After a screening period of 9-3 days, the
subjects will receive treatment with Rifampicin as single drug during 7 days (monotherapy).
This treatment will be followed by treatment with 7 days of Rifampicin and Isoniazid,
Pyrazinamide and Ethambutol (combination therapy), and 7-8 days treatment with standard TB
medication.
All subjects will be closely monitored for side effects. This monitoring will include daily
interviews and physical examination, and ECG evaluation and blood and urine analyses at
specific intervals.
During the 7 days of monotherapy, after the second day of the combination therapy and at the
end of the combination therapy, overnight sputum will be collected from the patients to
investigate the potency of high dose rifampicin to reduce this number of bacilli.
The Rifampicin dose will be increased step by step and group by group. The control group
will receive the standard dose of 10 mg Rifampicin/kg, whereas the first treatment group
will receive 20 mg/kg. The Rifampicin dose will only be further increased for a next group
of patients, if this is expected to be safe.
Rifampicin is widely available and not expensive. Physicians all over the world have
experience with this drug and its adverse effects. Should this study be successful, the
highest dose of Rifampicin that this safe and tolerable will be given to a larger group of
patients. in the next study.
If increasing the dose of Rifampicin proves to be safe and effective, a higher dose of
Rifampicin could be implemented broadly and quickly, and it would benefit many patients
worldwide.
TBTC Study 27/28 PK: Moxifloxacin Pharmacokinetics During TB Treatment [Completed]
This substudy of TBTC Studies 27 and 28 compares 1) the pharmacokinetics of moxifloxacin
alone versus moxifloxacin administered with rifampin in healthy volunteers and 2) the
pharmacokinetics of moxifloxacin among patients with tuberculosis being treated with
multidrug therapy (isoniazid or ethambutol, rifampin, and pyrazinamide) to those of healthy
volunteers receiving moxifloxacin plus rifampin. It also evaluates the association between
polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin pharmacokinetic parameters, the
effect of polymorphisms of MDR1 genotype and/or rifampin pharmacokinetics on isoniazid
pharmacokinetic parameters adjusted for N-acetyltransferase genotype (NAT2), and determines
by multivariate regression analyses the associations between moxifloxacin or rifampin
pharmacokinetic parameters and markers of tuberculosis disease severity including the
covariates of two-month culture positivity, cavitary lung disease, Body Mass Index, weight,
duration of study treatment prior to PK, co-morbidities and C-reactive protein. Healthy
volunteers and TB patients receive frequent scheduled blood draws during a 24 hour period
after ingesting a dose of TB drugs.
Reports of Suspected Pyrazinamide Side Effects
Acute Hepatic Failure (34),
Jaundice (18),
Pyrexia (16),
Hepatitis (16),
Hepatic Encephalopathy (13),
Paradoxical Drug Reaction (11),
Drug Rash With Eosinophilia and Systemic Symptoms (10),
Peritoneal Tuberculosis (9),
Hepatic Function Abnormal (8),
Hepatotoxicity (8), more >>
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