Antitubercular Agents ; pharmacology ; therapeutic use ; Child ; Drug Resistance, Multiple, Bacterial ; Drug Therapy, Combination ; Humans ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology

Objective: To evaluate the diagnostic accuracy of line probe assays for drug- resistant tuberculosis (TB) in China. Methods: Chinese databases (CNKI, Wanfang, SinoMed, VIP Information) and English databases (PubMed, Embase, Cochrane Library) were used to retrieve the literatures regarding the accuracy of line probe assays in the diagnosis of drug-resistant tuberculosis in China between January 1, 2000 and September 1, 2017. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the included studies. Sensitivity and specificity in different studies (using drug sensitivity test or gene sequencing as gold standard) were combined by Meta-analysis using bivariate or univariate model. In addition, subgroup analysis (GenoType MTBDRplus, GenoType MTBDRsl and Reverse dot blot hybridization) and sensitivity analysis were also carried out. Results: A total of 24 literatures involving 82 studies were included in the final analysis. The sensitivity and specificity of line probe assays for rifampicin resistant TB were 0.91(0.88-0.94) and 0.98 (0.97-0.99), respectively. The sensitivity and specificity of line probe assays for isoniazid resistant TB were 0.80 (0.77-0.83) and 0.98 (0.96-0.99), respectively. The sensitivity and specificity of line probe assays for multidrug-resistant TB were 0.81 (0.76-0.85) and 0.99 (0.99-1.00), respectively. The sensitivity and specificity of line probe assays for quinolone resistant TB were 0.92(0.88-0.95) and 0.94 (0.91-0.97), respectively. The sensitivity and specificity of line probe assays for second-line injectable drug resistant TB (including kanamycin, Capreomycin, amikacin) were 0.79(0.58-0.91) and 0.98 (0.90-1.00), respectively. The sensitivity and specificity of line probe assays for extensively drug-resistant TB were 0.46 (0.19-0.75) and 1.00 (0.98-1.00), respectively. Subgroup analysis showed that the overall diagnostic accuracy of GenoType MTBDRplus and GenoType MTBDRsl was higher than that of Reverse dot blot hybridization. According to the results of sensitivity analysis, the results of this study were robust. Conclusion: The diagnostic accuracy of line probe assays for drug-resistant TB is high.
Antitubercular Agents/therapeutic use* ; Biological Assay/methods* ; China ; Humans ; Isoniazid/pharmacology* ; Microbial Sensitivity Tests/methods* ; Mycobacterium tuberculosis/isolation & purification* ; Rifampin/pharmacology* ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.
Tuberculosis, Pulmonary/*drug therapy ; Time Factors ; Prospective Studies ; Middle Aged ; *Microbial Sensitivity Tests ; Male ; Humans ; Female ; Antitubercular Agents/pharmacology/*therapeutic use ; Aged ; Adult ; Adolescent

Antitubercular Agents ; pharmacology ; therapeutic use ; Diagnostic Techniques, Respiratory System ; Drug Approval ; Drug Resistance ; Female ; Gene Amplification ; Humans ; Immune Adherence Reaction ; Male ; Treatment Failure ; Tuberculosis ; diagnosis ; drug therapy ; genetics

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*

OBJECTIVETo compare the clinical characteristics of rifampin-dependent (R-dependent Mycobacterium tuberculosis) and rifampin-resistant (R-resistant Mycobacterium tuberculosis) patients with pulmonary tuberculosis.

METHODSThe clinical data including the demographic data, age groups, course of disease, history of chemotherapy with anti-TB drugs, and results of drug susceptibility test were collected from 61 cases of R-dependent pulmonary tuberculosis and 148 cases of R-resistant pulmonary tuberculosis treated between October, 2008 and January, 2012.

RESULTSMost of the R-dependent and R-resistant patients were between 30 and 44 years of age. The R-dependent patients included 12 receiving the first treatment patients and 49 with previous treatments, and the R-resistant patients included 11 without and 137 with previous treatments. The multi-drug resistant rate was 80.3% in R-dependent group, as compared to 92.6% in R-resistant group.

CONCLUSIONMost of the patients infected with R-dependent Mycobacterium tuberculosis are young or middle-aged, often having serious disease conditions. Detecting rifampin dependence is important for patients with initial treatment failure. Multi-drug resistance therapy guideline should be applied to patients infected with R-dependent Mycobacterium tuberculosis to improve the cure rate.

Adolescent ; Adult ; Aged ; Antitubercular Agents ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; drug effects ; Rifampin ; pharmacology ; therapeutic use ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology ; Tuberculosis, Pulmonary ; drug therapy ; microbiology ; Young Adult

OBJECTIVETo understand the determinants and epidemiology of drug-resistant tuberculosis (TB) in rural area.

METHODSAll the diagnosed TB patients in a county with directly observed treatment (DOTS) short-course program in 2002 and a sample of patients in another county without DOTS program located in northern Jiangsu province were surveyed with questionnaires. Drug susceptibility testing (DST) for positive cultures were performed by standardized proportion method. Univariable analysis and multivariate nonconditional logistic regression modeling were applied for data analysis.

RESULTSAmong the 152 patients with DST results, 32.9% of the cases showed resistance to at least one of the first-line anti-tuberculosis drugs with 26.3% to isoniazid, 18.4% to rifampin and 17.1% to both isoniazid and rifampin respectively. Previous treatments for TB and residence in the county without DOTS program were independent risk factors for isoniazid and rifampin resistance. TB patients showing indifferent to their health and delayed health seeking for more than 1 month were more likely to have rifampin resistance. Independent predictors of multidrug-resistant TB would include delayed health seeking for more than 1 month (OR = 4.66, 95% CI: 1.26 - 17.24), residing in the county without a DOTS program (OR = 3.01, 95% CI: 1.10 - 8.22), indifference to their health condition (OR = 5.13, 95% CI: 1.06 - 24.90) and suffering from chronic diseases (OR = 0.22, 95% CI: 0.05 - 0.87).

CONCLUSIONDrug-resistant TB was quite serious in this rural areas, mainly associated with man-made factors but partly due to the availability of the transmission.

Adult ; Antitubercular Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Ethambutol ; therapeutic use ; Humans ; Incidence ; Isoniazid ; therapeutic use ; Logistic Models ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Rifampin ; therapeutic use ; Rural Health ; Streptomycin ; therapeutic use ; Surveys and Questionnaires ; Tuberculosis, Pulmonary ; epidemiology ; microbiology

Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.
Antitubercular Agents ; therapeutic use ; Bacteria ; drug effects ; enzymology ; DNA-Directed RNA Polymerases ; metabolism ; Drug Discovery ; trends ; Drug Resistance, Bacterial ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Humans ; RNA, Bacterial ; Tuberculosis ; drug therapy ; enzymology

The goals of this study were to identify first-line drug resistance in new and previously treated tuberculosis (TB) cases and to determine risk factors for multidrugresistant TB (MDR-TB) at a private referral center in Korea. All patients with cultureconfirmed pulmonary TB over a 2-yr period between July 2002 and June 2004 were prospectively included in this study. In total, 637 patients were included; 512 (80.4%) were new cases, and 125 (19.6%) were previously treated cases. Resistance to at least one first-line drug was identified in 11.7% of new cases and 41.6% of previously treated cases. MDR-TB was detected in 3.9% of new cases and 27.2% of previously treated cases. The proportion of extensively drug-resistant TB among MDR-TB patients was 16.7% (9/54). Factors associated with MDR-TB included age under 45 yr, previous TB treatment, and the presence of cavitation on chest radiography. Rates of first-line drug resistance are high, particularly in previously treated patients, in the private sector in Korea. This underscores the need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antitubercular Agents/pharmacology/therapeutic use ; Drug Resistance, Bacterial ; Drug Resistance, Multiple ; Female ; Hospitals/statistics & numerical data ; Humans ; Korea/epidemiology ; Logistic Models ; Male ; Middle Aged ; Mycobacterium tuberculosis/*drug effects ; Prospective Studies ; Referral and Consultation ; Risk Factors ; Tuberculosis, Multidrug-Resistant/*drug therapy/epidemiology/microbiology ; Tuberculosis, Pulmonary/*drug therapy/microbiology