Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially fatal drug-induced systemic hypersensitivity response characterized by erythematous eruption, fever, leukocytosis with eosinophilia, and internal organ involvement. Antitubercular agents are potential causative agents for DRESS syndrome but difficult to verify as a culprit drug, since antitubercular agents are coadministered as a combination regimen. A 42-year-old female with endobronchial tuberculosis was diagnosed with DRESS syndrome after 4-week treatment of isoniazid, rifampicin, ethambutol, and pyrazinamide with prednisolone 50 mg. All the antitubercular agents were stopped and replaced with levofloxacin, cycloserine, p-aminosalicylic acid, and kanamycin. However, severe exacerbation of DRESS syndrome compelled the patient to discontinue the administration of the second-line antitubercular agents. Two months later, the patient underwent a patch test for all the antitubercular agents which had been used, and the results showed positivity to isoniazid and cycloserine. We report a rare case of DRESS syndrome that reacted to cycloserine as well as isoniazid. Development of coreactivity to other drugs should be differentiated with a flare-up reaction in the management of DRESS syndrome.
Adult ; Aminosalicylic Acid ; Antitubercular Agents ; Cycloserine ; Drug Hypersensitivity Syndrome ; Eosinophilia* ; Ethambutol ; Female ; Fever ; Humans ; Hypersensitivity ; Isoniazid ; Kanamycin ; Leukocytosis ; Levofloxacin ; Patch Tests ; Prednisolone ; Pyrazinamide ; Rifampin ; Tuberculosis

For the treatment of multidrug-resistant (MDR) tuberculosis, maintenance of appropriate antituberculous agents is essential because of its low cure rate and high dropout rate. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced systemic hypersensitivity response resulting in cessation of causative agents. In cases of second-line antituberculous agent-induced DRESS, it is extremely difficult to find other replacement medications to cure MDR tuberculosis. A 53-year-old male who had taken the second-line antituberculous agents (cycloserine, streptomycin, p-aminosalicylic acid, and prothionamide) as well as pyrazinamide for 5 weeks experienced DRESS syndrome accompanying hepatic coma. His symptoms improved with discontinuation of antituberculous agents and administration of high-dose methylprednisolone for 1 month. To resume the antituberculous medication, second-line antituberculous agents were administered one by one using a rapid desensitization protocol. While kanamycin, levofloxacin, and cycloserine were successfully readministered, p-aminosalicylic acid- and prothionamide-induced cutaneous hypersensitivity symptoms were relatively mild compared to previous reactions. Herein, we report a case of successfully treated MDR tuberculosis having a history of fatal DRESS syndrome to antituberculous agents using the rapid desensitization protocol.
Aminosalicylic Acid ; Antitubercular Agents ; Cycloserine ; Desensitization, Immunologic ; Drug Hypersensitivity Syndrome* ; Hepatic Encephalopathy ; Humans ; Hypersensitivity ; Kanamycin ; Levofloxacin ; Male ; Methylprednisolone ; Middle Aged ; Patient Dropouts ; Pyrazinamide ; Streptomycin ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. METHODS: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges. RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C2hr, 16.6+/-10.2 microg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2+/-1.5 microg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5+/-14.0 microg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0+/-29.1 microg/mL; all within or above); linezolid in three (mean C2hr, 11.4+/-4.1 microg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 microg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 microg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.
Adult ; Aged ; Amikacin ; Aminosalicylic Acid ; Capreomycin ; Cohort Studies ; Cycloserine ; Drug Monitoring* ; Ethionamide ; Female ; Humans ; Pharmacokinetics ; Retrospective Studies ; Tuberculosis ; Tuberculosis, Meningeal ; Tuberculosis, Multidrug-Resistant* ; Virginia* ; Linezolid

Adult ; Aminosalicylic Acid ; therapeutic use ; Female ; Humans ; Manganese Poisoning ; drug therapy

PURPOSE: The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management. METHODS: Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB. RESULTS: A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 case s (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05 ). CONCLUSION: The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.
Aged ; Aminosalicylic Acid ; Child ; Drug Resistance ; Ethambutol ; Extensively Drug-Resistant Tuberculosis ; Humans ; Incidence ; Isoniazid ; Korea ; Mycobacterium ; Mycobacterium tuberculosis ; Prevalence ; Pyrazinamide ; Rifampin ; Risk Factors ; Streptomycin ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

BACKGROUND: The purposes of the current study were to evaluate the concordant rates of anti-mycobacterial drug susceptibility test (DST) results in different solid media performed in different institutes, and to determine reliable susceptible testing methods. METHODS: One hundred and twenty two Mycobacterium tuberculosis strains were isolated from patients in A Hospital in 2005. DSTs were performed by the absolute concentration method using L?wenstein Jensen medium in both A Hospital (method A-1) and B Institute (method B-1) and by the proportion method using Middlebrook 7H10 agar in B Institute (method B-2). Nine drugs were used including isoniazid and rifampin. Sensitivity and specificity of each method were estimated by using the acceptable standard of 90% for isoniazid and rifampin and 80% for other drugs. The therapeutic outcomes of quinolone-administered patients were evaluated according to ofloxacin susceptibility results. RESULTS: Method B-1 showed sensitivity and specificity levels over the acceptable standard levels for all drugs. Method B-2 showed specificity lower than the acceptable levels for rifampin and cycloserine. Method A-1 showed specificity lower than the acceptable levels for isoniazid, streptomycin, p-aminosalicylic acid, and ofloxacin and sensitivity lower than the acceptable levels for prothionamide and cycloserine. The concordance rates of therapeutic outcomes with method B-1, method B-2, and method A-1 were 77%, 74%, and 65%, respectively. CONCLUSION: The drug susceptibility results for some drugs were discordant between the testing laboratories and media, requiring an urgent application of quality control programs to raise the reliability of anti-mycobacterial DST.
Academies and Institutes ; Agar ; Aminosalicylic Acid ; Culture Media ; Cycloserine ; Humans ; Isoniazid ; Mycobacterium tuberculosis ; Ofloxacin ; Prothionamide ; Quality Control ; Rifampin ; Sensitivity and Specificity ; Streptomycin

AIMTo prepare a new oral colon-specific delivery formulation and to investigate the release profile in vitro and the colon-specific delivery property in vivo in dogs.

METHODSSodium 4-aminosalicylic acid was selected as the model drug. The combination of Eudragit RL30D and RS30D were used as sustained-release film, and Eudragit FS30D used as enteric film, which was expected to release drug depending on pH and time. The release profile of tablets was studied in three phosphate buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak for 2 h in 0.1 mol x L(-1) HCl. The tablets were radiolabelled with 99mTc to make their release times and positions in the gastrointestinal tract be followed using a gamma camera.

RESULTSFor the in vitro study, there was no drug released in 0.1 mol x L(-1) HCl for 2 h, and release occurred slowly when pH was above 6.5. Drug was released faster while pH was higher. For the in vivo study, the coated tablets remained intact in the upper gastrointestinal tract, and drug release began after the colonic arrival. The uncoated tablets, however, disintegrated in the stomach of the dogs rapidly.

CONCLUSIONThe coating could protect the drug until the tablets reached the ascending colon, where drug was released slowly for over 10 h.

Acrylic Resins ; chemistry ; Administration, Oral ; Aminosalicylic Acid ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Antitubercular Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Colon ; metabolism ; Delayed-Action Preparations ; Dogs ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; Male ; Tablets, Enteric-Coated

BACKGROUND: Tuberculosis is still one of the most seriously threatening infections in Korea, because of multidrug resistant tuberculosis. Results of antituberculosis drug susceptibility test can provide clinicians very important informations for selection of proper regimens for treatment. METHODS: In this study the results of antituberculosis drug susceptibility test of 298 cases at Kyunghee Medical Center from 2000 to 2003 were retrospectively analysed to evaluate the trend of antituberculosis drug susceptibility. The procedure of drug susceptibility test was based on the absolute concentration method using Lowenstein-Jensen solid media. RESULTS: The resistance rate of Mycobacterium tuberculosis to one or more drugs was increased from 29.3% in 2000 to 48.2% in 2003, and the rates of multiple resistance to two or more drugs increased from 13.3% in 2000 to 20.5% in 2003. The increase in resistance rate to individual drug during study period were 20.0% to 24.1% in isoniazid, 9.3% to 19.3% in rifampicin, 5.3% to 15.7% in ethambutol, 4.0% to 10.8% in para-aminosalicylic acid, 2.7% to 6.0% in kanamycin, 1.3% to 7.2% in ethionamide, 1.3% to 6.0% in capreomycin, 1.3% to 7.2% in prothionamide, 0.0% to 12.1% in ofloxacin, 6.7%to 3.6% in streptomycin, 6.7% to 7.2% in cycloserine, 10.7% to 8.4% in pyrazinamide, respectively. CONCLUSIONS: The resistance rate of M. tuberculosis has been increased with years and multidrug resistant M. tuberculosis was commonly encountered in the specimens from the patients visited Kyunghee Medical center.
Aminosalicylic Acid ; Capreomycin ; Cycloserine ; Ethambutol ; Ethionamide ; Humans ; Isoniazid ; Kanamycin ; Korea ; Mycobacterium tuberculosis ; Ofloxacin ; Prothionamide ; Pyrazinamide ; Retrospective Studies ; Rifampin ; Streptomycin ; Tuberculosis

BACKGROUND: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequentl y co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MDR-Tb. METHODS: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A: 18.5 Aminosalicylic Acid ; Area Under Curve ; Chromatography, High Pressure Liquid ; Cycloserine ; Emaciation ; Fluoroquinolones ; Humans ; Kanamycin ; Ofloxacin* ; Pharmacokinetics* ; Prothionamide ; Streptomycin ; Tuberculosis, Multidrug-Resistant*

BACKGROUND: Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drags involving OFX. METHOD: A retrospective study was made through the regular follow up of smear positive cases,who treated by four drag, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(PAS). RESULTS: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advavanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78% , 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the duration of patients illness was less than 1 year, 1 to 3 years, 3 to 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52%. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). CONCLUSION: The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.
Abdominal Pain ; Aminosalicylic Acid* ; Communicable Diseases ; Cycloserine* ; Follow-Up Studies ; Humans ; Liver ; Nausea ; Prothionamide ; Pruritus ; Retreatment* ; Retrospective Studies ; Skin ; Sputum ; Tuberculosis, Pulmonary* ; Vomiting