Drug-resistant tuberculosis (TB) is still a major threat worldwide. However, recent scientific advances in diagnostic and therapeutic tools have improved the management of drug-resistant TB. The development of rapid molecular testing methods allows for the early detection of drug resistance and prompt initiation of an appropriate treatment. In addition, there has been growing supportive evidence for shorter treatment regimens in multidrug-resistant TB; and for the first time in over 50 years, new anti-TB drugs have been developed. The World Health Organization has recently revised their guidelines, primarily based on evidence from a meta-analysis of individual patient data (n=9,153) derived from 32 observational studies, and outlined the recommended combination and correct use of available anti-TB drugs. This review summarizes the updated guidelines with a focus on the medical management of drug-resistant TB.
Drug Resistance ; Extensively Drug-Resistant Tuberculosis ; Humans ; Methods ; Tuberculosis ; Tuberculosis, Multidrug-Resistant* ; World Health Organization

Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR)-TB and extensively drug resistant (XDR)-TB, poses a serious threat to global health because it requires treatment for a long duration and frequent hospitalization, and results in a considerable number of mortalities. In South Korea, MDR is observed in 2.7% of newly diagnosed TB cases and in 14% of re-treatment cases. In addition, 5~20% of MDR-TB could be categorized as XDR-TB. Treatment regimen for MDR or XDR-TB should include 4~5 drugs susceptible to isolated tuberculous bacilli and should be maintained at least 18 months after culture conversion. Pertinent combination of anti-TB drugs and solid compliance are the basis of successful treatment for MDR and XDR-TB patients.
Compliance ; Drug Resistance ; Extensively Drug-Resistant Tuberculosis ; Hospitalization ; Humans ; Republic of Korea ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

BACKGROUND: The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has become a serious worldwide problem. However, there is insufficient data regarding the current status of MDR-TB and XDR-TB in Korea. This study examined the recent status of MDR- and XDR-TB using the data from 7 laboratories, in which almost all drug susceptibility tests (DST) for Mycobacterium tuberculosis were performed. METHODS: The patients' identification data and DST results were collected from all 7 laboratories from 2001 to 2006 and the number of patients with MDR-TB and XDR-TB were calculated. RESULTS: The number of DSTs was 140,638 for 6 years with an increasing incidence each year (p<0.001). The number of DST with MDR results was 18,510 and personal identifying information was obtained in 16,640 (89.9%) tests. The number of MDR-TB patients from 2001 to 2006 was 2,329, 2,496, 2,374, 2,300, 2,354, and 2,178, respectively, when counting the duplications in a year as one patient. The number of MDR-TB patients when counting the duplications in 6 years as one patient was 2,281, 1,977, 1,620, 1,446, 1,512, and 1,373, respectively. When the same method was adopted, the number of XDR-TB patients was 191, 238, 282, 260, 272, and 264, respectively, and 189, 150, 130, 90, 122, and 110 patients, respectively. CONCLUSION: Despite the national efforts to control TB, there are still a large number of MDR- and XDR-TB patients in Korea.
Extensively Drug-Resistant Tuberculosis ; Humans ; Incidence ; Korea ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; Tuberculosis, Multidrug-Resistant

Multidrug-resistant tuberculosis (MDR-TB) is a great public health concern worldwide. MDR-TB denotes bacillary resistance to at least isoniazid and rifampicin. Extensively drug-resistant tuberculosis (XDR-TB) is MDR-TB with additional bacillary resistance to any fluoroquinolone and at least one second-line injectable drug. The treatment of MDR-TB requires prolonged administration of a toxic second line anti-tuberculosis drug and generally has poor outcomes. XDR-TB requires more complex treatment and has higher mortality. MDR- and XDR-TB arise because of inadequate or interrupted administration of first-line treatment and can be transmitted in the community. Thus, prevention of the emergence of resistance is the first principle in the management of MDR/XDR-TB. To prevent the emergence of drug resistance and transmission of MDR/XDR-TB, the adequate prescription of an anti-TB drug by a physician and good adherence of patients are essential. In addition, rapid diagnosis of drug resistance using molecular tests such as a line probe assay and Xpert MTB/RIF and the programmatic management of MDR/XDR-TB by designing an effective regimen using available drugs (a newer generation of fluoroquinolone, second-line injectable drugs, second-line oral drugs, and pyrazinamide) based on a guideline are an important strategy for controlling MDR/XDR TB. Despite the long duration of treatment, the treatment success rate of MDR-TB for patients who started treatment in 2009 has been 48% according to the World Health Organization. Thus, to improve the treatment outcomes of MDR/XDR-TB, new drug development is necessary.
Diagnosis* ; Drug Resistance ; Extensively Drug-Resistant Tuberculosis ; Humans ; Isoniazid ; Mortality ; Prescriptions ; Public Health ; Rifampin ; Tuberculosis, Multidrug-Resistant* ; World Health Organization

We aimed to analyze the drug resistance patterns of multidrug-resistant and extensively drug-resistant tuberculosis (TB) and the difference of drug resistance among various settings for health care in Korea. The data of drug susceptibility testing in 2009 was analyzed in order to secure sufficient number of patients from various settings in Korea. Patients were categorized by types of institutions into four groups, which comprised new and previously treated patients from public health care centers (PHC), the private sector, and Double-barred Cross clinics (DBC). The resistance rates to first-line drugs were uniformly high in every group. While the resistance rates to second-line drugs were not as high as first-line drugs, there was a pattern that drug resistance rates were lowest for PHC and highest for DBC. The differences of the resistance rates were more prominent for oral second-line drugs. Our findings implied that drug resistance to oral second-line drugs was significantly amplified during multidrug-resistant-TB treatment in Korea. Therefore, an individualized approach is recommended for treating drug-resistant-TB based on susceptibility testing results to prevent acquisition or amplification of drug resistance.
Delivery of Health Care ; Drug Resistance* ; Extensively Drug-Resistant Tuberculosis* ; Humans ; Korea* ; Private Sector ; Public Health ; Tuberculosis, Multidrug-Resistant

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

OBJECTIVES: Extensively drug-resistant tuberculosis (XDR-TB) is more expensive and difficult to treat than multidrug-resistant tuberculosis (MDR-TB), and outcomes for patients are much worse; therefore, it is important that clinicians understand the magnitude and distribution of XDR-TB. We conducted a retrospective study to compare the estimated incidence of and risk factors for M/XDR-TB with those of susceptible TB controls. METHODS: Sputum culture and drug susceptibility testing (DST) were performed in patients with known or suspected TB. Strains that were identified as MDR were subjected to DST for second-line drugs using the proportion method. RESULTS: Among 1,442 TB patients (mean age, 46.48 ± 21.24 years) who were culture-positive for Mycobacterium tuberculosis, 1,126 (78.1%) yielded isolates that were resistant to at least one first-line drug; there were 33 isolates (2.3%) of MDR-TB, of which three (0.2%) were classified as XDR-TB. Ofloxacin resistance was found in 10 (0.7%) isolates. Women were 15% more likely than men to yield M/XDR-TB isolates, but this difference was not significant. In a multivariate analysis comparing susceptible TB with X/MDR-TB, only one variable—the number of previous treatment regimens—was associated with MDR (odds ratio, 1.06; 95% confidence interval, 1.14–21.2). CONCLUSION: The burden of M/XDR-TB cases is not sizeable in Iran. Nonetheless, strategies must be implemented to identify and cure patients with pre-XDR-TB before they develop XDR-TB. Our results provide a greater understanding of the evolution and spread of M/XDR-TB in an environment where drug-resistant TB has a low incidence.
Extensively Drug-Resistant Tuberculosis* ; Female ; Humans ; Incidence ; Iran* ; Male ; Methods ; Multivariate Analysis ; Mycobacterium tuberculosis ; Ofloxacin ; Retrospective Studies ; Risk Factors* ; Sputum ; Tuberculosis* ; Tuberculosis, Multidrug-Resistant

The global emergence of multidrugresistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB threatens to derail the efforts of TB control programmes worldwide. From 2000 to 2010, 161 pulmonary MDR-TB cases (including six XDR-TB cases) were reported in Singapore, and of these, 80% occurred among the foreign-born, with an increasing trend seen after 2004. Among new pulmonary TB cases, the highest incidence of MDR-TB occurred among patients from Myanmar (8%), followed by Vietnam (4.4%) and China (2.3%), while among those previously treated, the highest incidence was found in patients from Vietnam (50%), followed by Indonesia (33%) and Bangladesh (33%). Although the proportion of Singapore-born pulmonary TB cases with MDR-TB has remained comparatively low (0.2% and 1.3% in new and previously treated cases, respectively), there is no room for complacency. Top priority must be accorded toward the proper treatment of drug-susceptible TB cases under strict programme conditions so as to prevent the development of MDR-TB in the first place.
Antitubercular Agents ; therapeutic use ; Emigrants and Immigrants ; Extensively Drug-Resistant Tuberculosis ; epidemiology ; Humans ; Mycobacterium tuberculosis ; Singapore ; epidemiology ; Tuberculosis, Multidrug-Resistant ; drug therapy ; epidemiology ; transmission

Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration required compared with drug-susceptible TB. The efficacy of treatment for MDR-TB is poorer than that for drug-susceptible TB. The selection of drugs in MDR-TB is based on previous treatment history, drug susceptibility results, and TB drug resistance patterns in the each region. Recent World Health Organization guidelines recommend the use of least 4 second-line drugs (a newer fluoroquinolone, an injectable agent, prothionamide, and cycloserine or para-aminosalicylic acid) in addition to pyrazinamide. The kanamycin is the initial choice of injectable durgs, and newer fluoroquinolones include levofloxacin and moxifloxacin. For MDR-TB, especially cases that are extensively drug-resistant, group 5 drugs such as linezolid, clofazimine, and amoxicillin/clavulanate need to be included. New agents with novel mechanisms of action that can be given for shorter durations (9-12 months) for MDR-TB are under investigation.
Clofazimine ; Cycloserine ; Drug Resistance ; Extensively Drug-Resistant Tuberculosis ; Fluoroquinolones ; Kanamycin ; Levofloxacin ; Linezolid ; Prothionamide ; Pyrazinamide ; Tuberculosis ; Tuberculosis, Multidrug-Resistant* ; World Health Organization

Antitubercular Agents/therapeutic use* ; China/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Extensively Drug-Resistant Tuberculosis ; Humans ; Kanamycin Resistance ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; Ofloxacin/pharmacology* ; Tuberculosis, Multidrug-Resistant/epidemiology*