Clinical experience with extensively Drug Resistant tuberculosis (XDR-TB) has not been reported in Malaysia before. We describe the clinical characteristics, risk factors, progress and therapeutic regimen for a healthcare worker with XDR-TB, who had failed therapy for multidrug resistant TB (MDR TB) in our institution. This case illustrates the risk of TB among healthcare workers in high TB-burden settings, the importance of obtaining upfront culture and susceptibility results in all new TB cases, the problem of acquired drug resistance developing during MDR-TB treatment, the challenges associated with XDR-TB treatment regimens, the value of surgical resection in refractory cases, and the major quality of life impact this disease can have on young, economically productive individuals.
Extensively Drug-Resistant Tuberculosis

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), resistant to at least the two main TB drugsisoniazid and rifampicin, has been a threat to TB control because the treatment requires more toxic drugs and longer period with poor treatment outcomes. Recently, more serious concerns have been raised about extensively drug resistant-tuberculosis (XDR-TB), which shows resistance to fluoroquinolones and aminoglycosides in addition to isoniazid and rifampicin. XDR-TB is a serious global health threat because the cure is very difficult as few sensitive anti-TB drugs remain. XDR-TB develops when first-and second-line anti-TB drugs are misused during the course of treatment, most commonly due to poor compliance of the patients to the treatment regimen. People with XDR-TB can pass the XDR-TB bacteria to other people. Thus, every effort should be made to prevent the development of XDR-TB by establishing an effective TB control program maximizing patient adherence to prescribed anti-TB regimen and minimizing contact of XDR-TB patients with other people to prevent the spread of XDR-TB.
Aminoglycosides ; Bacteria ; Compliance ; Extensively Drug-Resistant Tuberculosis ; Fluoroquinolones ; Humans ; Isoniazid ; Patient Compliance ; Rifampin ; Tuberculosis

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

BACKGROUND: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. METHODS: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. RESULTS: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. CONCLUSIONS: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.
Diagnosis ; Extensively Drug-Resistant Tuberculosis* ; Korea* ; Linezolid* ; Methods ; Microbial Sensitivity Tests* ; Mycobacterium tuberculosis ; Polymerase Chain Reaction ; Tuberculosis

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