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 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

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 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

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

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

BACKGROUND: Joint symptoms frequently occur in the course of antituberculous chemotherapy and tend to be ignored and overlooked, but in some cases, they are often very troublesome in obstructing ordinary life. Joint symptoms that develop during antituberculous chemotherapy need to be understood, but there are few materials describing them systematically. METHOD: This study enrolled 33 patients with tuberculosis treated with first line antituberculous agents for more than 6months. In the course of treatment, joint symptoms not associated with specific cause, such as pre-existing joint disease or trauma, were investigated and compared with those of the asymptomatic group, We confirmed the incidence of joint symptoms and factors associated with them. RESULTS: Nineteen of 33 patients (58%) had joint symptoms. Joint symptoms developed 1.9±1.4 months after the beginning of chemotherapy and lasted for 3.6±2.5 months. IN 18 of 19 symptomatic patients, multiple joints were involved : shoulder(10 patients, 53%), knee(10,53%), finger(6,32%). Joint symptoms were expressed as pain(19 patients, 100%), stiffness(7,37%) and/or swelling (3,16%). Fourteen patients (74%) took analgesics to relieve their symptoms and in 2 patients, antituberculous agents were discontinued because of the severity of their symptoms. The symptoms seem to be caused by agents other than pyrazinamide, but it was very difficult to identify the definite causative agent. In age, sex, underlying disease and serum uric acid level, no significant differences were noted between the two groups. CONCLUSIONS: Although joint symptoms are common during antituberculous chemotherapy, their development is difficult to predict. Because some joint symptoms can become very bothersome, the physician should pay close attention to these symptoms.
Analgesics ; Arthralgia ; Drug Therapy* ; Humans ; Incidence ; Joint Diseases ; Joints* ; Pyrazinamide ; Tuberculosis ; Uric Acid

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*

The incidence of drug-resistant tuberculosis (DR-TB) in pediatric populations is a critical indicator of national TB management and treatment strategies. Limited data exist regarding the rate of pediatric DR-TB. In this study, we aimed to analyze the status of DR-TB in Korean children from 2007 to 2013. We analyzed specimens submitted to the Korean Institute of Tuberculosis using Mycobacterium tuberculosis culture and drug susceptibility tests (DSTs) from January 2007 through December 2013. Specimens from patients ≤ 19 years of age were included. Among the 2,690 cases, 297 cases were excluded because of insufficient data, leaving 2,393 cases for the final analysis. In total, resistance to one or more TB drugs was 13.5%. The resistance rates of each of the drugs were as follows: isoniazid (INH) 10.2%, rifampin (RFP) 5.1%, ethambutol (EMB) 3.7%, and pyrazinamide (PZA) 3.1%. The resistance rate of multidrug-resistant TB (MDR-TB) was 4.2%, and that of extensively drug-resistant TB (XDR-TB) was 0.8%. The overall drug resistance rate demonstrated significant increase throughout the study period (P < 0.001) but showed no significant difference compared to previous study from 1999 to 2007. The drug resistance rate of PZA in ≤ 15 years of age group was significantly greater than that of > 15 years (P < 0.001). The drug resistance rate has increased throughout the study period.
Adolescent* ; Child* ; Drug Resistance ; Ethambutol ; Humans ; Incidence ; Isoniazid ; Mycobacterium tuberculosis ; Pyrazinamide ; Rifampin ; Tuberculosis ; Tuberculosis, Multidrug-Resistant*