Background: Rifampicin, isoniazid, and pyrazinamide are oral essential anti-tuberculosis drugs on single or combined preparations. Worldwide research has shown that the plasma concentration of anti-tuberculosis drugs with daily therapeutic doses were seen significant lower than permitted in tuberculosis patients, especially for rifampicin and isoniazid. Objective: To investigate plasma concentration of rifampicin, isoniazid, and pyrazinamide in pulmonary tuberculosis and pleural tuberculosis patients. Methods: Determine plasma concentration of rifampicin, isoniazid, and pyrazinamide at 2 hours after administration in 168 tuberculosis patients by the HPLC method. Identify prevalence of low plasma concentrations of anti-tuberculosis drugs. Results: There was a wide range of plasma concentration of rifampicin, isoniazid, and pyrazinamide in the tuberculosis patients. The mean plasma concentration of rifampicin was 6.13 \xb1 4.66 microgram/ml, of isoniazid was 2.99 \xb1 1.94 microgram/ml, pyrazinamide was 38.98 \xb1 18.39 microgram/ml. There was no significant differences in the plasma concentration of rifampicin, isoniazid, and pyrazinamide in groups of pulmonary tuberculosis and pleural tuberculosis patients. Percentage of patients with plasma concentration below therapeutic concentration was 76.83% of rifampicin, 51.85% of isoniazid, 10.13% of pyrazinamide. There were 12.03% of patients who had pyrazinamide concentration higher than the therapeutic range. Conclusions: There was a wide range of plasma concentration in rifampicin, isoniazid, and pyrazinamide of tuberculosis patients. Low plasma concentration of rifampicin and isoniazid are common. It may be necessary to optimize the drug dose by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.
tuberculosis ; rifampicin ; isoniazid ; pyrazinamide

A HPLC method has been used to quantify plasma rifampicin and isoniazid and pyrazinamide simultaneously. Extraction of rifampicin in plasma samples was done as follows: mix 1ml of plasma containing rifampicin and 1.5 ml acetonitril on a vortex mixer for 1 minute prior to centrifugation at 3500 rpm for 30 minutes. The organic layer was filtered through 0.45m filter membrane and then 30l of this solution was injected into the HPLC system. The chromatographic conditions were as follows: in stationary phase: column: Apollo Alltech RP18 (250 x 4.6 mm; 5 m); in mobile phase: methanol - phosphate buffet solution containing 0.02M potassium dihydrogen phosphate adjusted to pH 4.5 by adding phosphoric acid (65: 35); Flow rate: 1.0 ml/min and UV detector: 254 nm
Chromatography, High Pressure Liquid ; lasma ; Pyrazinamide ; Isoniazid ; Rifampin

The study was conducted to compare bioavailability of rifampicin at the same doses with and without isoniazid and pyrazinamide in the standard separate tablets in 12 healthy volunteers. Bioavailability of rifampicin was estimated by plasma concentration of rifampicin from 0h to 24h after administration. Plasma rifampicin concentration was determined by HPLC method. The results revealed that Cmax and AUC for rifampicin was reduced (31.24% and 25.95%, respectively) when rifampicin - isoniazid - pyrazinamide was administeredat the same time. It was concluded that bioavailability of rifampicin was affected by presence of isoniazid and pyrazinamide.
Tuberculosis ; Tuberculosis, Multidrug-Resistant ; Pyrazinamide ; Rifampin ; Biological ; Availability

A marked low concentration of serum uric acid(0.7-1.2mg/dl) was detected in a 14-year-old boy with recurrent episodes of gross hematuria. The hypouricemia accompanied with a markedly increased urinary clearance of uric acid (32.6-56.0ml/min), which was only minimally changed after both the administration of pyrazinamide, and inhibitor of the renal tubular secretion of uric acid, and the administration of probenecid, and inhibitor of the renal tubular reabsorption of uric acid. Other renal tubular functions were normal. There were no other family members with hypouricemia. Thies is the first case report of isolated renal hypouricemia due to presecretory reabsorption defect of uric acid in the renal proximal tubule in Korea. And renal hypouricemia should be included in the diagnosis of hematuria.
Adolescent ; Diagnosis ; Hematuria* ; Humans ; Korea ; Male ; Probenecid ; Pyrazinamide ; Uric Acid

Drug-induced thrombocytopenia and purpura have boon developed by many various agents. Rifampin and Pyrazinamide have been known as bactericidal antituberculous drugs, but, the above side effects have been a problem. Especially, hematologic side effects art fatal to patients occasionally. Rifampin-induced thrombocytopenia and purpura have been well known, also, pyrazinamide-induced thrombocytopenia have been reported. A new quilonone agent Ciprofloxacin, has been commonly used in clinics now, but it's side effects are not known well. So, we report a case of a 23-year-old female with thrombocytopenia and purpura after taking Rifampin, Pyrazinamide, and Ciprofloxacin as antituberculous agents.
Ciprofloxacin* ; Female ; Humans ; Purpura* ; Pyrazinamide* ; Rifampin ; Thrombocytopenia* ; Young Adult

INTRODUCTION: Development of drug resistance is one of the most important barriers in achieving global control of tuberculosis (TB). Continuous surveillance, such as observation of susceptibility and resistance patterns to anti-TB drugs, together with nationwide programs aimed at TB case identification, treatment and control, physician and patient education, is a valuable tool in the goal towards reducing TB prevalence and mortality.
OBJECTIVE: It is the aim of this study to determine the prevalence rate and resistance pattern of  first line anti-tuberculosis drugs in a tertiary hospital in Manila, Philippines
MATERIALS AND METHODS: Records of specimens submitted for Mycobacterium tuberculosis (MTB) culture and sensitivity, using BACTEC TM MGIT TM 960 SIRE Kit and PZA Kit, at the Section of Clinical Pathology, University of Santo Tomas Hospital, were reviewed. Isolates cultured for MTB were subjected to sensitivity studies to rifampicin (R),isoniazid (H), ethambutol (E), pyrazinamide (Z) and streptomycin (S).
RESULTS: A total of 546 specimens were cultured for MTB and sent for sensitivity studies. Majority of the specimens were from pulmonary sources (77%). Overall resistance rate was 52.38% (n=286). One-drug resistance was 23.26% (n= 127; highest with R followed by H); two-drug resistance was 15.38% (n=84; highest with H-R); three-drug resistance was 8.61% (n=47; highest with H-R-E and H-R-S); four-drug resistance was 4.58% (n=25; highest with H-R-E-S) and five-drug resistance (H-R-E-S-Z) rate was 0.55% (n=3). 
CONCLUSION: The University of Santo Tomas Hospital, as a referral facility, is encountering an increasing number of drug-resistant tuberculosis from 2003 to 2013.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Ethambutol ; Mycobacterium Tuberculosis ; Isoniazid, Pyrazinamide, Rifampin Drug Combination ; Pyrazinamide ; Isoniazid ; Rifampin ; Streptomycin ; Pathology, Clinical ; Tuberculosis

We report a case of tuberculosis verrucosa cutis in a 39-year-old male patient, who presented verrucous plaque on the dorsum of right third finger. Seven months ago, he had a cut with paper and skin lesion developed. Histopathologic features revealed parakeratosis, irregular acanthosis in the epidermis and inflammatory cellular infiltrates and tuberculoid granulomas in the dermis. AFB- positive bacilli were demonstrated. He has been treated with isoniazid, rifampicin, ethambutol, and pyrazinamide for 4 months till now and the skin lesion has been markedly improved.
Adult ; Dermis ; Epidermis ; Ethambutol ; Fingers ; Granuloma ; Humans ; Isoniazid ; Male ; Parakeratosis ; Pyrazinamide ; Rifampin ; Skin ; Tuberculosis*

We report a case of tuberculosis verrucosa cutis in a 35-year-old male patient who presented itchy verrucous plaque over both buttocks. Skin biopsy revealed hyperkeratosis, parakeratosis, and irregular acanthosis in the epidremis, and inflammatory infiltration and noncaseating tuberculoid granulomas in the dermis. Several AFB-positive bacilli were detected. He was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide for 4 months till now and the verrucous skin lesions have been markedly improved.
Adult ; Biopsy ; Buttocks ; Dermis ; Ethambutol ; Granuloma ; Humans ; Isoniazid ; Male ; Parakeratosis ; Pyrazinamide ; Rifampin ; Skin ; Tuberculosis*

BACKGROUND: The drug resistance rate in tuberculosis patients with history of chemotherapy is an important indicator of for evaluation of appropriateness of treatment regimens and compliance of patients. This study examined the long-term changes in the drug resistance rates among TB patients failed in treatment or reactivated. METHODS: The results of drug susceptibility testing data from patients registered in health centers from 1981 to 2004 were analyzed. RESULTS: The rate of resistance to isoniazid decreased from 90% to 20%, and the resistance to ethambutol decreased from 45% to 6%. The rate of resistance to rifampicin varied from 13% to 28% and the resistance to pyrazinamide was 5% to 10%. Multidrug resistance was about 2-3% lower than any rifampicin resistance rates. The second-line drug resistance was ranged from 1% to 3%. There was no difference between patients' genders. Patient numbers per 100,000 population increased with age. The regional distribution was even at 4-6 patients per 100,000 population, and drug resistance rates were significantly lower in big city areas than in small towns and rural areas. CONCLUSION: The rates of resistance of Mycobacterium tuberculosis isolated from TB patients with history of chemotherapy to isoniazid, rifampin, ethambutol, and isoniazid plus rifampin were significantly decreased during over two decades.
Compliance ; Drug Resistance ; Drug Resistance, Multiple ; Drug Therapy ; Ethambutol ; Humans ; Isoniazid ; Mycobacterium tuberculosis ; Pyrazinamide ; Rifampin ; Tuberculosis*

BACKGROUND: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. METHODS: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. RESULTS: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. CONCLUSION: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.
Animals ; Ethambutol ; Isoniazid ; Lung ; Mice ; Pyrazinamide ; Rifampin ; Spleen ; Sprains and Strains ; Stem Cells ; Treatment Outcome ; Tuberculosis