RESUMEN
The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant Mycobacterium tuberculosis clinical isolates from four European hospitals were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.
Asunto(s)
Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Compuestos de Espiro/farmacología , Tiazinas/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Secuencia de Bases , Cartilla de ADN/genética , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple/genética , Europa (Continente) , Genes Bacterianos , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/enzimología , Mycobacterium tuberculosis/genética , Racemasas y Epimerasas/genéticaRESUMEN
INTRODUCTION: Diagnosing tuberculosis in low-resource settings mostly relies on sputum smear microscopy. Improvement through capacity building is a priority. This project aimed to strengthen tuberculosis diagnosis at an intermediate level laboratory. METHODOLOGY: The Italian National Institute for Infectious Diseases and the Italian Development Cooperation closely collaborated with regional and national institutions and reference laboratories to provide laboratory setup, equipment and reagents, personnel training, and the implementation of culture and quality assessment programs at Dodoma Regional Hospital, Dodoma, Tanzania. RESULTS: Microscopy sensitivity was increased, personnel were trained, and culture techniques and quality assessment programs were introduced. CONCLUSIONS: Implementing tuberculosis diagnosis in resource-constrained settings is feasible and represents a basis for further strengthening.