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*

A retrospective analysis was performed in two major HIV/AIDS referral hospitals in Beijing to evaluate the prevalence of Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections in HIV-infected patients. A total of 627 patients' data were reviewed, and 102 (16.3%) patients were diagnosed with culture-confirmed mycobacterial infection, including 84 with MTB, 16 with NTM, and 2 with both MTB and NTM. The most frequent clinical complication by mycobacterial infection was pulmonary infection (48/102, 47.1%). The overall rates of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were 11.9% and 3.4%, respectively. This study underlines the urgent need to intensify screening for mycobacteria coinfection with HIV and to prevent the spread of drug-resistant TB among HIV-infected patients.
AIDS-Related Opportunistic Infections ; epidemiology ; microbiology ; Adult ; Beijing ; Coinfection ; Extensively Drug-Resistant Tuberculosis ; epidemiology ; microbiology ; Female ; HIV Infections ; epidemiology ; microbiology ; Hospitals, Urban ; Humans ; Male ; Mycobacterium Infections, Nontuberculous ; epidemiology ; microbiology ; Mycobacterium tuberculosis ; isolation & purification ; Nontuberculous Mycobacteria ; isolation & purification ; Prevalence ; Retrospective Studies ; Sputum ; microbiology ; Tuberculosis, Multidrug-Resistant ; epidemiology ; microbiology ; Tuberculosis, Pulmonary ; epidemiology ; microbiology

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

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

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

BACKGROUND: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. METHODS: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on Löwenstein-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. RESULTS: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). CONCLUSION: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.
Diagnosis ; Drug Resistance ; Drug Resistance, Microbial ; Extensively Drug-Resistant Tuberculosis ; Humans ; Isoniazid ; Korea* ; Methods ; Mycobacterium tuberculosis* ; Mycobacterium* ; Rifampin ; Sputum ; Tertiary Care Centers* ; Tuberculosis

A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed.
Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; *Drug Discovery ; *Drug Repositioning ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/microbiology

BACKGROUND/AIMS: We evaluated the trend in the rates of drug-resistant tuberculosis (TB) over time, as well as the difference in the drug-resistance pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) at a private referral center in South Korea. METHODS: All patients with culture-confirmed TB from 2006 to 2013 were included. RESULTS: In total, 1,745 patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of previously treated cases, respectively. The MDR TB rate during the study period decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in previously treated cases. No difference in the drug-resistance rate was detected between PTB and EPTB. CONCLUSIONS: The TB drug-resistance rate, particularly that of MDR TB, remained high at a private referral hospital, and the drug-resistance rate did not decrease significantly from 2006 to 2013. This finding underscores the need for a national survey regarding the prevalence of drug-resistant TB to obtain the most accurate and current drug-resistance status in South Korea, including the private sector.
Adult ; Aged ; Antitubercular Agents/*therapeutic use ; *Drug Resistance, Multiple, Bacterial ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Female ; Hospitals, Private ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mycobacterium tuberculosis/*drug effects/isolation & purification ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; *Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/epidemiology/*microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/epidemiology/*microbiology

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

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