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

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

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

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

Tuberculous (TB) pleuritis is the second most common form of extrapulmonary tuberculosis. Because the yield of pleural fluid mycobacterial culture is as low as 20% and the pleural biopsy is rather invasive, the measurement of adenosine deaminase (ADA) has been a cornerstone of the diagnosis of TB pleuritis. If the ADA level of pleural fluid is higher than 70 IU/L, the diagnosis of TB pleuritis can be made safely. The treatment is based on a standard short course anti-TB treatment starting with isoniazid, rifampicin, ethambutol, and pyrazinamide. Although systemic steroids and drainage of pleural fluid have been tried to reduce the residual pleural thickening, the results are contradicting.
Adenosine Deaminase ; Biopsy ; Drainage ; Ethambutol ; Isoniazid ; Pleural Effusion ; Pleurisy ; Pyrazinamide ; Rifampin ; Steroids ; Tuberculosis

We report a case of exercise-induced acute renal failure associated with renal hypouricemia in a 35- year-old man who complained of oliguria and back pain after swimming. Laboratory tests revealed that serum blood urea nitrogen and creatinine level were elevated, the serum uric acid concentration was subnormal(2.1 mg/dL). After conservative treatment, renal function was recovered. But, uric acid level decreased to 0.4 mg/dL. In addition, there was no supression of urate clearance to creatinine clearnace ratio(CUA/CCr) following the administration of pyrazinamide, and no increase of CUA/CCr after benzbromarone. Therefore, we think the cause of renal hypouricemia in this patient may be the subtotal defect in the urate transport.
Acute Kidney Injury* ; Back Pain ; Benzbromarone ; Blood Urea Nitrogen ; Creatinine ; Humans ; Oliguria ; Pyrazinamide ; Swimming ; Uric Acid

Gynecomastia is a benign enlargement of the male breast attributable to proliferation of the ductal elements. Gynecomastia has been rarely reported as an adverse effect of isoniazid therapy. We report the case of a 35-year-old man who was prescribed with isoniazid, rifampicin, ethambutol and pyrazinamide to treat pulmonary and lymphatic tuberculosis. After five months of treatment, the patient complained of painful engorgement in the bilateral breasts and the presence of male gynecomastia was confirmed with a physical examination and radiographical methods. The serum level of estradiol was also increased. Common causes of male gynecomastia were excluded through history taking and the laboratory findings. The anti-TB drugs were changed to a second line regimen due to radiographical progression and the intolerance of the patient to gynecomastia. Gynecomastia was relieved very slowly and a tender subareolar palpable mass decreased in size and consistency over five-month period after stopping the probable causative drug, isoniazid. From a review of the literature, gynecomastia has been shown to be a side effect of treatment with first line anti-tuberculosis drugs, and especially with isoniazid. We report the rare case.
Adult ; Breast ; Estradiol ; Ethambutol ; Gynecomastia ; Humans ; Isoniazid ; Male ; Physical Examination ; Pyrazinamide ; Rifampin ; Tuberculosis

BACKGROUNDDrug susceptibility assay is very important in tuberculosis therapy. Pyrazinamide is a first line antituberculosis drug and diagnosis of its resistance in Mycobacterium tuberculosis (M. tuberculosis) is difficult and time consuming by conventional methods. In this study, we aimed to evaluate the performance of the microscopic observation drug susceptibility (MODS) assay in the detection of pyrazinamide resistance in M. tuberculosis relative to the conventional Wayne assay and Lowenstein-Jensen (LJ) proportion method.

METHODSM. tuberculosis clinical isolates (n = 132) were tested by the MODS and the Wayne assay: the results were compared with those obtained by the LJ proportion method. Mutations in the gene were identified by direct sequencing of the pncA genes of all isolates in which pyrazinamide resistance was detected by any of the three methods.

RESULTSCompared to the LJ results, the sensitivity and specificity of the MODS assay were 97.8% and 96.5% respectively; the sensitivity and specificity of the Wayne assay were 87.0% and 97.7% respectively. Mutations in the pncA gene were found in 41 of 46 strains that were pyrazinamide resistant (3 tests), in 1 of the 4 strains (LJ only), in 42 of 48 strains (at least 1 test), but no mutations in 1 strain sensitive according to the MODS assay only. The MODS assay, Wayne assay and LJ proportion method provided results in a median time of 6, 7 and 26 days respectively.

CONCLUSIONSMODS assay offers a rapid, simple and reliable method for the detection of pyrazinamide resistance in M. tuberculosis and is an optimal alternative method in resource limited countries.

Antitubercular Agents ; pharmacology ; Microbial Sensitivity Tests ; Microscopy ; methods ; Mycobacterium tuberculosis ; drug effects ; Pyrazinamide ; pharmacology