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.
- SourceAvailable from: Dmitry A Gryadunov[Show abstract] [Hide abstract]
ABSTRACT: Steadily growing resistance of the tuberculosis causative agent towards a broad spectrum of antituberculosis drugs calls for rapid and reliable methods for identifying the genetic determinants responsible for this resistance. In this study, we present a biochip-based method for simultaneous identification of mutations within rpoB gene associated with rifampin resistance, mutations in katG, inhA, ahpC genes responsible for isoniazid resistance, mutations within the regions of gyrA and gyrB genes leading to fluoroquinolones resistance, and mutations in the rrs gene and the eis promoter region associated with the resistance to kanamycin, capreomycin and amikacin. The oligonucleotide microchip, as the core element of this assay, provides simultaneous identification of 99 mutations in the format “one sample—one PCR—one microchip”, and it makes it possible to complete analysis of multidrug-resistant and extensively drug-resistant tuberculosis within a single day. The tests on 63 Mycobacterium tuberculosis clinical isolates with different resistance profiles using the developed approach allows us to reveal the spectrum of drug-resistance associated mutations, and to estimate the significance of the inclusion of extra genetic loci in the determination of M. tuberculosis drug resistance.Molecular Biology 03/2014; 48(2-2):214-226. · 0.74 Impact Factor
- Enfermedades Infecciosas y Microbiología Clínica 04/2013; · 1.48 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