“…In other words, 90% of patients with rifampin-resistant TB had MDR-TB. For this reason, rifampin resistance serves as a marker for the diagnosis of MDR-TB by several techniques (26,27). In our study, however, only 60% to 70% of cases of rifampin-resistant TB in the four sites in this study were resistant to isoniazid, which might be due to the relatively high rates and differentiation of M. tuberculosis in China, which might show a different drug resistance pattern than those observed in other countries.…”
e Drug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), is still one of the most serious threats to TB control worldwide. Early diagnosis of MDR-TB is important for effectively blocking transmission and establishing an effective protocol for chemotherapy. Genechip is a rapid diagnostic method based on molecular biology that overcomes the poor biosafety, time consumption, and other drawbacks of traditional drug sensitivity testing (DST) that can detect MDR-TB. However, the Genechip approach has not been effectively evaluated, especially in limited-resource laboratories. In this study, we evaluated the performance of Genechip for MDR-TB in 1,814 patients in four prefectural or municipal laboratories and compared its performance with that of traditional DST. The results showed that the sensitivity and specificity of Genechip were 87.56% and 97.95% for rifampin resistance and 80.34% and 95.82% for isoniazid resistance, respectively. In addition, we found that the positive grade of the sputum smears influenced the judgment of results by Genechip. The test judged only 75% of the specimens of "scanty" positive grade. However, the positive grade of the specimens showed no influence on the accuracy of Genechip. Overall, the study suggests that, in limited-resource laboratories, Genechip showed high sensitivity and specificity for rifampin and isoniazid resistance, making it a more effective, rapid, safe, and cost-beneficial method worthy of broader use in limited-resource laboratories in China.
“…In other words, 90% of patients with rifampin-resistant TB had MDR-TB. For this reason, rifampin resistance serves as a marker for the diagnosis of MDR-TB by several techniques (26,27). In our study, however, only 60% to 70% of cases of rifampin-resistant TB in the four sites in this study were resistant to isoniazid, which might be due to the relatively high rates and differentiation of M. tuberculosis in China, which might show a different drug resistance pattern than those observed in other countries.…”
e Drug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), is still one of the most serious threats to TB control worldwide. Early diagnosis of MDR-TB is important for effectively blocking transmission and establishing an effective protocol for chemotherapy. Genechip is a rapid diagnostic method based on molecular biology that overcomes the poor biosafety, time consumption, and other drawbacks of traditional drug sensitivity testing (DST) that can detect MDR-TB. However, the Genechip approach has not been effectively evaluated, especially in limited-resource laboratories. In this study, we evaluated the performance of Genechip for MDR-TB in 1,814 patients in four prefectural or municipal laboratories and compared its performance with that of traditional DST. The results showed that the sensitivity and specificity of Genechip were 87.56% and 97.95% for rifampin resistance and 80.34% and 95.82% for isoniazid resistance, respectively. In addition, we found that the positive grade of the sputum smears influenced the judgment of results by Genechip. The test judged only 75% of the specimens of "scanty" positive grade. However, the positive grade of the specimens showed no influence on the accuracy of Genechip. Overall, the study suggests that, in limited-resource laboratories, Genechip showed high sensitivity and specificity for rifampin and isoniazid resistance, making it a more effective, rapid, safe, and cost-beneficial method worthy of broader use in limited-resource laboratories in China.
“…This mutation ranks first in RMP-resistant strains globally, although its frequencies differ between different geographic locations. The mutation is highly prevalent in Kazakhstan (80.9%) (28), Taiwan (66.7%) (29), Italy (59.5%) (30), and China (59.1%) (15); equally common in South Korea (53.1%) (20), Brazil (52.4%) (31), Bangladesh (52.3%) (12), and Australia (52%) (9); and somewhat rarer in Spain (42.6%) (32), Russia (41.5%) (33), Mexico (40.4%) (34), Vietnam (37.8%) (35), and Hungary (31%) (36).…”
Resistance of to rifampin (RMP), mediated by mutations in the gene coding for the beta-subunit of RNA polymerase, poses a serious threat to the efficacy of clinical management and, thus, control programs for tuberculosis (TB). The contribution of many individual mutations to the development and level of RMP resistance remains elusive. In this study, the incidence of mutations throughout the gene among 115 clinical isolates, both resistant and susceptible to RMP, was determined. Of the newly discovered mutations, the role of three substitutions in the causation of RMP resistance was empirically tested. The results from mutagenesis experiments were combined with the assessment of the prevalence of mutations, and their reciprocal co-occurrences, across global populations. Twenty-two different types of mutations in the gene were identified and distributed among 58 (89.2%) RMP-resistant strains. The MICs of RMP were within the range of 40 to 800 mg/liter, with MIC and MIC values of 400 and 800 mg/liter, respectively. None of the mutations (Gln429His, Met434Ile, and Arg827Cys) inspected for their role in the development of RMP resistance produced an RMP-resistant phenotype in isogenic H37Rv strain-derived mutants. These mutations are supposed to compensate for fitness impairment incurred by other mutations directly associated with drug resistance.
“…The last one had a complete deletion of this gene, a mechanism rarely found associated with clinical INH-resistance [26,27]. By sequencing, the distinction of three clones each carrying one peculiar mutation in the ahpC gene is consistent with the hypothesis that up regulation mutations in the ahpC promoter compensate for the loss of catalase-peroxidase activity encoded by the katG gene [28]. …”
BackgroundIt is estimated that Lao People’s Democratic Republic (Lao PDR) ranks fifth among the seven countries most affected by TB in the WHO Western Pacific Region. However, because of late implementation of mycobacterial culture, no study on resistance to anti-TB drugs had been performed yet. The objective of this study was to document drug resistance rate among patients hospitalized for pulmonary TB in threeprovinces of Lao PDR.MethodsA cross-sectional study was conducted in three sites, one central and two regional hospitals, from April to November 2010. For each TB suspected patient sputum smear microscopy and culture on Lowenstein-Jensen media were performed. GenoType® MTBDRplus assay was used to test the susceptibility to isoniazid (INH) and rifampicin (RMP), GenoType® MTBDRsl for second-line drugs and GenoType® Mycobacterium CMAS for non-tuberculous mycobacteria (NTM).ResultsOut of 104 positive culture on Lowenstein-Jensen, 87 (83.6%) were M. tuberculosis and 17 (16.4%) were NTM. Of 73 new TB cases, 5 isolates (6.8%) were resistant to INH. Of 14 previously treated cases, 2 isolates (14.3%) were resistant to INH and one isolate was XDR.ConclusionDespite an overall rate of resistance still moderate, the frequency of mutations conferring INH monoresistance and identification of the first strain of XDR require strengthening surveillance of drug resistant tuberculosis in Lao PDR.
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