Rifampicin-resistant Mycobacterium tuberculosis: susceptibility to isoniazid and other anti-tuberculosis drugs.
ABSTRACT Based on data from 14 Supranational Tuberculosis (TB) Reference Laboratories worldwide, the proportion of rifampicin (RMP) resistant isolates that were isoniazid (INH) susceptible by phenotypic drug susceptibility testing varied widely (0.5-11.6%). RMP-resistant isolates that were INH-susceptible had significantly lower rates of resistance to other first- and second-line anti-tuberculosis drugs (except rifabutin) compared to multidrug-resistant isolates. RMP resistance is not always a good proxy for a presumptive diagnosis of multidrug-resistant TB, which has implications for use of molecular assays that identify only RMP resistance-associated DNA mutations.
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ABSTRACT: Line probe assays(LPA), nucleic acid tests used for the rapid diagnosis of tuberculosis(MTB), non-tuberculosis mycobacteria(NTM) and MTB drug resistance, have limited performance data in HIV-infected individuals, in whom paucibacillary tuberculosis(TB) is common. In this study, the strategy of testing sputum with GenoType MTBDRplus(MTBDR-Plus) and GenoType Direct(Direct) was compared to a gold standard of 1 mycobacterial growth indicator(MGIT) liquid culture. HIV+ TB suspects from Southern Africa and South America with <7 days of TB treatment had 1 sputum tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical mycobacterial speciation, and culture-based drug susceptibility testing (DST). Of 639 participants, 59.3% were MGIT MTB culture positive, of which 276 (72.8%) were AFB smear positive. MTBDR-Plus had sensitivity of 81.0% and specificity of 100%, with sensitivity of 44.1% in AFB smear negative vs. 94.6% in AFB smear positive. For specimens that were positive for MTB by MTBDR-Plus, sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) 70.6% and 99.1%. The Direct LPA had sensitivity of 88.4% and specificity of 94.6% for MTB detection, with a sensitivity of 72.5% in smear negative specimens. 10/639 MGIT cultures grew M.avium complex or M.kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in HIV infection, including in AFB smear negative specimens, with 72.5% sensitivity for MTB identification with Direct LPA and 44.1% with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.Journal of clinical microbiology 01/2014; · 4.23 Impact Factor
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ABSTRACT: Childhood multidrug-resistant (MDR) tuberculosis is an emerging disease with increasing numbers being recognized. This review presents recent developments in childhood MDR tuberculosis. New molecular-based diagnostic tests, although not optimal, have reduced the difficulty in confirming the diagnosis of MDR tuberculosis in children. However, the importance of making a diagnosis of probable MDR tuberculosis has been reaffirmed by contact tracing studies showing 80-90% of child contacts of MDR tuberculosis cases who develop disease have MDR tuberculosis themselves. Prevention of MDR tuberculosis in child contacts with appropriate preventive treatment regimens is supported by new observational data and deserves further study. When diagnosed and treated appropriately, outcomes for MDR tuberculosis and even extensively drug-resistant tuberculosis in children are good, despite limited pharmacokinetic data on second-line drugs. Novel anti-tuberculosis drugs and regimens are becoming available and should be studied in children for dose-finding and safety. Recording and reporting of MDR tuberculosis in children are frequently poor, leading to inaccurate estimates of disease burden and suboptimal resource planning. Rapid diagnosis and appropriate treatment results in good outcomes in the majority of children with MDR tuberculosis. Additional research on optimal diagnosis, prevention and treatment of MDR tuberculosis in children remains a high priority.Current Opinion in Infectious Diseases 04/2014; · 5.03 Impact Factor
- Enfermedades Infecciosas y Microbiología Clínica 04/2013; · 1.48 Impact Factor