Antituberculosis Drug Resistance in Pulmonary Isolates of Mycobacterium tuberculosis, Cuba 2012-2014.

INTRODUCTION Systematic surveillance of antituberculosis drug resistance allows identification of multidrug-resistant and extensively drug-resistant isolates of Mycobacterium tuberculosis. Surveillance studies of antituberculosis drug resistance systematically conducted in Cuba for over 15 years have revealed low circulation of multidrug-resistant tuberculosis, under 1% in new cases. OBJECTIVE Characterize antituberculosis drug resistance in isolates of M. tuberculosis recovered from patients with pulmonary tuberculosis in Cuba in 2012-2014. METHODS The nitrate reductase assay was used to test 997 isolates of M. tuberculosis for sensitivity to isoniazid and rifampicin. Isolates identified as multidrug resistant were tested for sensitivity to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, amikacin, kanamycin and capreomycin by the proportion method, as well as genetic resistance mutations in rpoB, katG, inhA, gyrA, rrs and embB genes, using GenoType MTBDRplus and MTBDRsl commercial kits. RESULTS Some 95.6% of isolates from new cases and 89.6% of isolates from previously treated patients were sensitive to isoniazid and rifampicin. Multidrug resistance was found in 0.8% of new and 5.2% of previously treated patients, a statistically significant difference. One extensively drug-resistant isolate was detected among previously treated cases. All isolates examined with the molecular method had mutations in the rpoB gene, which is associated with resistance to rifampicin; only seven showed mutations in the katG gene and one in the inhA gene associated with isoniazid resistance. In one isolate, we found mutations in both gyrA and rrs genes, which are associated with resistance to fluoroquinolones and second-line injectable drugs and therefore, extensive resistance. CONCLUSIONS Results corroborate the low frequency of multidrug-resistant and extensively resistant M. tuberculosis strains in Cuba and highlight the need for continuous improvement of surveillance of antituberculosis drug resistance in Cuba. KEYWORDS Mycobacterium tuberculosis, multidrug resistance, extensively drug-resistant tuberculosis, Cuba.

Drug-resistant tuberculosis in Cuba. Results of the three global projects.

SETTING: The spread of multidrug-resistant tuberculosis (MDR TB) in the world remains a major public health problem. Surveillance of anti-TB drug resistance is therefore an essential tool for monitoring the effectiveness of TB control program and, through policy development, for improving national and global TB control. OBJECTIVE: To determine the prevalence of anti-TB drug resistance in Cuba during the execution of the three global projects. DESIGN: Drug-resistance was determined using the proportion method in 1528 Mycobacterium tuberculosis strains to first line anti-TB drugs. RESULTS: Resistance in new cases was 8.3%, 4.6% and 5.0%; MDR was 0.7%, 0% and 0.3% in the first (1997), second (2000) and third (2004) global projects, respectively. In new cases, none showed resistance to the four drugs. There were among previously treated cases statistically significant decreases in the prevalence of resistance to at least one drug when comparing the results obtained in the three global projects. CONCLUSIONS: The contributed data through Cuba demonstrated that our country is relatively free of MDR strains, reflecting the good National Control Program and the possibility of TB elimination in Cuba.

[Surveillance of resistance of Mycobacterium tuberculosis to anti-TB drugs in Cuba, 1995-1998]. / Vigilancia de la resistencia de Mycobacterium tuberculosis a las drogas antituberculosas en Cuba, 1995-1998.

Drug-resistance surveillance by means of culture and drug susceptibility test (DST) allows the estimation of the regional and global magnitude of multidrug-resistance (MDR). Two reports on anti-tuberculosis drug resistance by the WHO/IUATLD showed that drug-resistance TB varied widely across regions. This work determined the prevalence of drug resistance among new cases and among previously treated cases of tuberculosis in Cuba during the period 1995-1998. Drug resistance was determined using the proportion method in 1379 Mycobacterium tuberculosis strains to first line antituberculosis drugs (isoniazid, streptomycin, ethambutol and rifampicin). The resistance in new cases was 8.3% and 6.5%; MDR was 0.7% and 0% in the first and second study respectively. The contributed data through Cuba demonstrated that our country is relatively free of MDR strains, recognizing it to world level the good tuberculosis-control programs and the success of the application in our country of the directly-observed-treatment strategy from the year 1971.

Vigilancia de la resistencia de Mycobacterium tuberculosis a las drogas antituberculosas en Cuba, 1995-1998

L a vigilancia de la resistencia a fármacos a través del cultivo y de las pruebas de susceptibilidad in vitro permite conocer la magnitud regional y mundial de la resistencia en tuberculosis. En el presente trabajo se determinó la prevalencia de la resistencia a fármacos antituberculosos en Cuba, durante el periodo 1995-1998 en casos nuevos y en aquéllos que han recibido tratamiento previo. Los resultados incluidos en este estudio forman parte de los dos proyectos mundiales organizados por la OMS/UICTER. La resistencia a los medicamentos se evaluó usando el método de las proporciones en 1.379 cepas de Mycobacterium tuberculosis a los fármacos de primera línea (isoniacida, rifampicina, estreptomicina y etambutol). La resistencia en casos nuevos fue del 8,3% y 6,5% y la resistencia múltiple a fármacos ( multidrug-resistance, MDR) fue del 0,7% y 0% en el primer y segundo estudio, respectivamente. Estos resultados permitieron demostrar la escasa circulación de cepas MDR en Cuba; se reconoció a nivel mundial el buen funcionamiento del Programa Nacional de Control y el éxito de la aplicación en nuestro país de la estrategia del tratamiento estrictamente supervisado desde 1971.

Surveillance of resistance of Mycobacterium tuberculosis to anti-TB drugs in Cuba, 1995-1998 Drug-resistance surveillance by means of culture and drug susceptibility test (DST) allows the estimation of the regional and global magnitude of multidrug-resistance (MDR). Two reports on anti-tuberculosis drug resistance by the WHO/IUATLD showed that drug-resistance TB varied widely across regions. Thecurrent study determined the prevalence of drug resistance among new cases and among previously treated cases of tuberculosis in Cuba during the period 1995-1998. Using the proportion method, drug resistance was determined in 1,379 Mycobacterium tuberculosis strains to four front-line anti- tuberculosis drugs (isoniazid, streptomycin, ethambutol and rifampicin). In two separate studies, the overall resistance in new cases was 8.3% and 6.5%, and the MDR was 0.7% and 0%, respectively. The Cuba data demonstrated that Colombia, in comparison, is relatively free of MDR strains, indicating effective tuberculosis control programs in Colombia and the success of the direct observation-treatment strategy that has been in continuous use since 1971.