ABSTRACT
This publication presents the results of the Chilean initial study of resistance to first line anti-tuberculous drugs. The study was carried out between 2011 and 2012 by the National Reference Laboratory of the Institute of Public Health, as part of the Drug Surveillance Resistance in tuberculosis (TB) promoted by the World Health Organization. Methodology: Cross-sectional study performed using cluster sampling, representative of the entire country as recommended by the World Health Organization. Susceptibility testing to isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide was performed through the proportion method or Wayne's enzymatic method, as appropriate. Results: 594 susceptibility tests were performed, showing an overall level of TB drug resistance of 8.6% and a prevalence of multidrug resistance of 1.3%. Indeed, the study showed a decrease in streptomycin resistance and an increase of isoniazid resistance in both mono-resistance and accumulated resistance compared to previous studies. No cases of mono-resistance to rifampicin were detected. Conclusion: An increased resistance to anti-TB drugs in Chile is observed, which despite being still low, is no less worrisome. Since 2014 the monitoring of drug resistance to TB is universally performed to avoid sub - diagnosis and treat each case according to the susceptibility profile.
Esta publicación presenta los resultados del estudio de resistencia inicial a fármacos anti-tuberculosos de primera línea realizado entre los años 2011 y 2012 en Chile por el Laboratorio de Referencia Nacional del Instituto de Salud Pública, estudio que forma parte de la vigilancia de la fármaco-resistencia en tuberculosis (TBC) promovida por la Organización Mundial de la Salud. Metodología: Estudio transversal realizado mediante un muestreo por conglomerado, representativo de todo el país según recomendaciones de la Organización Mundial de la Salud. Se realizó prueba de susceptibilidad a isoniacida, rifampicina, estreptomicina, etambutol y pirazinamida a través del método de las proporciones o método enzimático de Wayne según corresponda. Resultados: Se realizó test de susceptibilidad a 594 casos de TBC, observándose una resistencia inicial global de 8,6% y una prevalencia de multi-resistencia de 1,3%. Además destaca la caída en la resistencia a estreptomicina y el aumento de la resistencia a isoniacida, tanto en mono-resistencia como en resistencia acumulada para ambos fármacos comparada con los estudios anteriores. No se observaron casos de mono-resistencia a rifampicina. Conclusión. Se observa un aumento de la resistencia a fármacos anti-tuberculosos en Chile la que, a pesar de ser aún baja, no deja de ser preocupante. Desde el año 2014 la vigilancia de fármaco-resistencia para TBC se hace en forma universal, de modo de evitar el sub-diagnóstico y realizar un tratamiento de acuerdo al perfil de susceptibilidad de cada caso.
Subject(s)
Humans , Antitubercular Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/microbiology , Chile , Cross-Sectional Studies , Microbial Sensitivity Tests , Mycobacterium tuberculosis/classification , Sputum/microbiologyABSTRACT
Background: The incidence of acquired resistance to antituberculous drugs of Mycobacterium tuberculosis in Chile is approximately 23 percent. Aim: To analyze the mutations associated with drug resistance in drug resistant strains of Mycobacterium tuberculosis. Material and Methods: In 28 drug resistant Mycobacterium tuberculosis strains isolated in Chile, genes leading to drug resistance were studied. DNA was amplifed by polymerase chain reaction (PCR) and sequencing was carried out using the ABI PRISM big dye terminator cycle sequencing ready reaction kit. Results: In rifampicin-resistant strains, the mutations in rpoβ gene were in the codons S531W/L (56 percent), D516Y (16 percent) and D516V (16 percent). The predominant mutation in katG gene was in the codon S315L (73 percent) in isoniazid-resistant strains. The mutation S95T was found in the 71 percent of ciprofoxacin resistant strains. Only one ethambutol resistant strain had the M306I mutation. Three unreported mutations in katG were identifed. Conclusions: Drug resistance associated mutations of Mycobacterium tuberculosis isolated in Chile were similar to those reported abroad.