Tuberculosis (TB), a chronic communicable disease, continues to be a global public health concern. Slow decline of TB incidence and prevalence, human immunodeficiency virus/TB coinfection, growth of multidrug-resistant/extensively-resistant TB have made the control of TB even more challenging. Chemotherapy of TB has developed for decades and now also faces similar challenges.
Antitubercular Agents ; therapeutic use ; Coinfection ; Humans ; Prevalence ; Public Health ; Tuberculosis ; drug therapy ; epidemiology ; Tuberculosis, Multidrug-Resistant ; drug therapy ; epidemiology

OBJECTIVETo investigate the distribution of the Beijing genotypes of Mycobacterium tuberculosis (M. tuberculosis) and the relationships between Beijing genotype strains and drug-resistant phenotypes in China.

METHODSClinical isolates were collected during a 9-month research period from April to December in 2008 in six geographic regions of China. One isolate that had been biochemically confirmed to be a member of the M. tuberculosis complex was collected from each patient. The demographic data of the patients (eg. sex, age, and history of tuberculosis) as well as the drug resistance patterns and sources of the clinical isolates were collected. Drug susceptibility testing was performed using proportion method. Beijing genotypes of M. tuberculosis were identified by spacer oligonucleotide typing or insertion of IS6110 in the genomic dnaA-dnaN locus.

RESULTSAmong the 410 M. tuberculosis clinical isolates, 67.1% (275/410) isolates were Beijing genotypes of M. tuberculosis. Significantly larger proportions of tuberculosis patients were infected with Beijing genotypes in the northeastern regions of China than that of in the central-western regions (chi2 = 20.50, P = 0.000). No significant associations were found either between Beijing genotype strains and patients' age, sex, or treatment history. Multidrug-resistant isolates and rifampin-resistant isolates were more common among Beijing genotype strains than among non-Beijing strains (P = 0.002, P = 0.005).

CONCLUSIONSAbout two third of the clinical isolates of M. tuberculosis in China are Beijing genotypes. Beijing genotype strains are not correlated with patients' age, sex, treatment history. People living in the northeastern regions of China are more susceptible to Beijing genotypes than those living in the central-western of China. Beijing genotype strains tend to be rifampin-resistant or multidrug-resistant.

Antitubercular Agents ; pharmacology ; China ; Genotype ; Humans ; Mycobacterium tuberculosis ; classification ; genetics ; Phenotype ; Rifampin ; pharmacology ; Tuberculosis ; drug therapy ; Tuberculosis, Multidrug-Resistant ; genetics

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

OBJECTIVES: To estimate the resistance rate and to correlate the clinical characteristics of resistant tuberculosis with the patients of pulmonary tuberculosis who were referred to the university hospital. METHODS: We prospectively performed sensitivity tests for all patients who were diagnosed as active tuberculosis by sputum smear or sputum culture from January, 1995 to June, 1996. Patients profile, previous treatment history, patterns of drug resistance, initial chest films and other clinical findings were analysed. RESULTS: Overall, 24(26.0%) of the 92 patients had resistance to at least one drug and 8(8.6%) had resistance to isoniazid(INH) and rifampin(RFP). Among the 66 patients without previous tuberculosis therapy, 11(16.6%) were drug-resistant and 2(3.0%) were multi-drug resistant. Among the 26 patients with previous therapy, 13(50.0%) were drug-resistant and 6(23.0%) were multi-drug resistant. For all 92, resistance to INH was most common (19.5%), followed by RFP (9.7%) and ethambutol (9.7%). Drug resistance was significantly high in previously treated patients and in cavity-positive patients. Treatment failure was also high in previously treated patients with resistant tuberculosis. In patients with primary resistance, treatment failure was not observed. CONCLUSION: Sensitivity tests are strongly recommended in all culture positive patients with previous therapy but, in patients with primary resistance, sensitivity tests are not required. Proper combination chemotherapy should be given under careful surveillance.
Adolescence ; Adult ; Aged ; Antitubercular Agents/pharmacology ; Female ; Hospitals, University ; Human ; Korea/epidemiology ; Male ; Middle Age ; Prospective Studies ; Tuberculosis, Multidrug-Resistant/epidemiology* ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Pulmonary/epidemiology* ; Tuberculosis, Pulmonary/drug therapy

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

OBJECTIVE: To systematically review the diagnostic accuracy of Xpert^® Mycobacterium tuberculosis/rifampicin (Xpert^® MTB/RIF) for the detection of active tuberculosis (TB) and rifampicin-resistance TB in Chinese patients. METHODS: Four Chinese databases (SinoMed, CNKI, WanFang database, and VIP) and three English databases (PubMed, Embase, and The Cochrane Library) were searched from January 1, 2000 to September 15, 2017, to identify diagnostic tests about the accuracy of Xpert^® MTB/RIF in Chinese patients. Two investigators screened the articles and extracted the information independently, and then the quality of each included study was evaluated by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Bivariate random-effects meta-analysis was conducted to pool the sensitivity and specificity. In addition, subgroup analyses were performed based on patient type (TB patient and TB suspected patient), sample type (sputum, bronchoalveolar lavage fluid and others). All statistical analyses were conducted with Stata version 13.0. RESULTS: A total of 47 articles were included in this systematic review. Most of them (38 articles) were in Chinese and only 9 articles were in English. All the articles were published during 2014 to 2017, and the sample size ranged from 31 to 3 151. Forty articles including 42 comparisons about TB were finally included with the pooled sensitivity of 0.94 (95%CI: 0.92, 0.95) and the pooled specificity of 0.87 (95%CI: 0.84, 0.91). Subgroup analysis showed that different patient and specimen types had no significant differences on sensitivity, but the specificity of sputum group was higher than that of bronchoalveolar lavage fluid. As for the detection of rifampicin-resistant TB, 33 articles (38 comparisons) were analyzed, the pooled sensitivity and specificity were 0.92 (95%CI: 0.89, 0.94) and 0.98 (95%CI: 0.97, 0.99) respectively. There were no significant differences between the patient and specimen in the subgroup analyses. The Deeks funnel plot showed a possible publication bias for detecting active tuberculosis (P=0.08) and no publication bias for rifampicin-resistant TB (P=0.24). The likelihood ratio scatter gram showed that in clinical applications, Xpert^® MTB/RIF had a good diagnostic ability for detecting active tuberculosis, and it had good clinical diagnostic value in detecting rifampicin-resistant TB. CONCLUSION Xpert^® MTB/RIF has good sensitivity and specificity in detecting TB and rifampicin-resistant TB in Chinese people. In particular, it has good clinical value in diagnosing rifampicin-resistance TB.
Antibiotics, Antitubercular/therapeutic use* ; China ; Diagnostic Tests, Routine ; Drug Resistance, Bacterial ; Humans ; Rifampin/pharmacology* ; Sensitivity and Specificity ; Tuberculosis/drug therapy* ; Tuberculosis, Multidrug-Resistant/drug therapy* ; Tuberculosis, Pulmonary/drug therapy*

Aged ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Pneumoconiosis ; drug therapy ; microbiology ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology

BACKGROUND: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. METHODS: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. RESULTS: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. CONCLUSION: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.
Base Sequence ; Codon ; Drug Resistance, Multiple ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Korea* ; Mycobacterium tuberculosis* ; Mycobacterium* ; Rifampin ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

BACKGROUNDThe Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries. However, there were little data obtained by validation or demonstration study of the assay in China. In this study, the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province, China.

METHODSConsecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB, three sputum specimens (one spot sputum, one night sputum, and one morning sputum) were collected and each sputum was tested with smear microscopy, Löwenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across subgroups and testing methods, 95% confidence intervals were calculated. All analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant.

RESULTSFor case detection, the sensitivity of Xpert MTB/RIF was 100% for smear- and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients. The specificity was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria. For the detection of rifampin resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by MDR-TB.

CONCLUSIONSThe Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance, which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in China. Further evaluations in county-level laboratories for implementing the assay are still required.

Adult ; Antibiotics, Antitubercular ; therapeutic use ; China ; Female ; Humans ; Male ; Middle Aged ; Rifampin ; therapeutic use ; Tuberculosis ; diagnosis ; drug therapy ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary ; diagnosis ; drug therapy ; Young Adult

BACKGROUND: Para-aminosalicylic acid(PAS) is a 2nd-line drug that can cause severe adverse reactions leading to poor patient compliance. This study evaluated the relapse rate according to the discontinuance of PAS at a certain point after bacteriological conversion during the course of chemotherapy for multidrug-resistant tuberculosis(MDR-TB). METHODS: 42 out of 452 MDR-TB patients were enrolled in this study. All subjects were receiving chemotherapy including PAS at National Masan TB Hospital between Jan. 1, 2000 and Dec. 31, 2001. The relapse rate was evaluated after the discontinuance of PAS from their initial regimen as a result of the severe adverse reactions at a certain point after the bacteriological conversion during the course of chemotherapy for MDR-TB. RESULTS: The male to female ratio was 2.5:1, and the mean age was 47.2 years old. The average number of past histories, used drugs and resistant drugs was 1.2, 3.9 and 4.3. The mean number of sensitive drugs included in the inirial regimen was 3.9. The mean time for bacteriological conversion and discontinuance of the PAS was 2.3 months after initiating treatment and 6 months after bacteriological conversion, respectively. There was no relapse after discontinuing PAS during a mean follow up period of 31.6 months. CONCLUSION: PAS may be discontinued in the cases of serious gastrointestinal problems approximately 6 months after bacteriological conversion without concern about relapse.
Compliance ; Drug Therapy* ; Female ; Follow-Up Studies ; Humans ; Male ; Patient Compliance ; Recurrence* ; Retrospective Studies* ; Tuberculosis, Multidrug-Resistant