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: 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

Last two decades have witnessed the resurging of tuberculosis (TB) and multi-drug resistant TB, even the extensive drug resistant TB. It is urgent to develop novel drug to combat the increasingly worsen TB. Capreomycin is an ideal second-line TB drug. It is also recognized as an attractive template to develop more peptide antibiotics. In this review, the biosynthesis gene cluster of capreomycin, the action mechanism unveiled by transcriptome and novel resistance rational are summarized from the recent functional genomic investigation.
Antibiotics, Antitubercular ; chemistry ; pharmacology ; Capreomycin ; chemistry ; pharmacology ; Drug Resistance, Multiple, Bacterial ; drug effects ; Genes, Bacterial ; Mycobacterium tuberculosis ; drug effects ; genetics ; Open Reading Frames ; Ribosomal Proteins ; metabolism ; Tuberculosis, Multidrug-Resistant ; drug therapy