Emergence of Heteroresistance Mycobacterium Tuberculosis in Saudi Arabia

Purpose: Heteroresistant Mycobacterium tuberculosis (MTB) is defined as a group of drug-susceptible and resistant bacteria in a single clinical specimen from tuberculosis (TB) patients. Heteroresistance of MTB is considered a preliminary stage to full resistance. The present study aimed to determine the heteroresistance in Mycobacterium tuberculosis in Tabuk province, in the north of the Kingdom of Saudi Arabia. Method: GenoType MTBDRplus assay was used to determine mutations associated with isoniazid and rifampicin resistance. Results: A total number of 46 confirmed M. tuberculosis positive sputum samples were scanned for heteroresistance. The present study revealed 3 (6.5%) heteroresistant mutations to either rpoB gene alone, 2 (4.4%) to rpoB and 1 (2.2%) to inhA genes. Conclusion: The detection of heteroresistant mutations could guide the initiation of an appropriate regimen of treatment.

Mutaciones que confieren resistencia a fármacos antituberculosis de primera línea en Perú: una revisión sistemática de la literatura

Objetivos. Sistematizar la información disponible referente a las mutaciones que confieren resistencia a los fármacos antituberculosis de primera línea. Materiales y métodos. Se realizó una revisión sistemática de la literatura científica para identificar artículos que reportaron mutaciones que confieren resistencia a fármacos antituberculosis de primera línea. Esta búsqueda hizo énfasis en la resistencia a los fármacos de isoniazida y rifampicina en cepas de M. tuberculosis de pacientes peruanos. La búsqueda fue realizada en PubMed y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). Resultados. Se incluyeron 14 artículos de los cuales tres reportaron mutaciones asociadas con resistencia a isoniazida, seis a rifampicina, ocho a pirazinamida y uno a etambutol. Todas las mutaciones a isoniazida o rifampicina fueron identificadas directa o indirectamente mediante la prueba de diagnóstico molecular GenoType MTBDRplus® v2.0. La mayor variabilidad de mutaciones fue determinada en la resistencia a pirazinamida. Conclusiones. Existe una gran variabilidad de mutaciones asociadas con resistencia a fármacos antituberculosis que han sido reportadas en Perú, y se sistematizan en el presente reporte. Estas mutaciones deben de ser tomadas en cuenta para el desarrollo de dispositivos diagnósticos o selección de pruebas diagnósticas a ser aplicadas en nuestro país.

Evaluation of GeneXpert MTB/RIF system performances in the diagnosis of extrapulmonary tuberculosis

Background Tuberculosis represents a serious public health problem and a significant diagnostic and therapeutic challenge worldwide. Molecular diagnostic techniques are crucial in the World Health Organization’s new tuberculosis control strategy. This study aims to evaluate the performance of GeneXpert MTB/RIF (Cepheid Sunnyvale, CA, United States) in diagnosis of extra-pulmonary tuberculosis then compare it’s performance in detecting Rifampicin resistance to GenoType MTBDRplus (HAIN Life Sciences, Nehren, Germany). Methods Samples from pulmonary and/or extra-pulmonary origins were analysed in a 21 months retrospective study. Samples were sent to the bacteriology laboratory for Mycobacterium tuberculosis detection using conventional bacteriological and molecular methods (GeneXpert MTB/RIF and MTBDRplus). Sensitivity and specificity were calculated for the stained smear and GeneXpert according to culture (Gold Standard) as well as for GeneXpert MTB/RIF in both negative and positive microscopy tuberculosis cases. Data’s statistical analysis was performed with SPSS13.0 software. Results Seven hundred fourteen patients’ samples were analysed; the average age was 47.21 ± 19.98 years with a male predominance (66.4%). Out of 714 samples: 285 were from pulmonary and 429 were from extra-pulmonary origins. The positivity rates for microscopy, GeneXpert MTB/RIF and culture were 12.88, 20.59 and 15.82%, respectively. These rates were 18.9, 23.85 and 20.35% for pulmonary samples and 9.71, 18.41 and 12.82% for extra-pulmonary samples, respectively. The sensitivity and specificity of GeneXpert MTB/RIF were almost the same in both pulmonary and extra-pulmonary samples (78.2 and 90.4%) and (79,3 and 90.3%) respectively. Rifampicin resistance rate found by GeneXpert MTB/RIF was 0.84%. Comparison of Rifampicin resistance obtained by GeneXpert MTB/RIF and Genotype MTBDRplus, showed 100% agreement between the two techniques for studied samples. Conclusions This confirms GeneXpert MTB/RIF advantage for tuberculosis diagnosis, particularly extra-pulmonary tuberculosis with negatively stained smear. The performance of GeneXpert and Genotype MTBDRplus are similar in detection of Rifampicin resistance. However, variability of detection performance according to tuberculosis endemicity deserves more attention in the choice of screening techniques of Rifampicin resistance, hence the interest of conducting comparative studies of detection performance under low and medium endemicity on large samples of tuberculosis populations.

Early Discontinuation of Ethambutol in Pulmonary Tuberculosis Treatment Based on Results of the GenoType MTBDRplus Assay: a Prospective, Multicenter, Noninferiority Randomized Trial in South Korea

ABSTRACT No studies have investigated whether the discontinuation of ethambutol (EMB) based on susceptibility to isoniazid and rifampin, as determined by the GenoType MTBDRplus assay, would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of the intensive phase of treatment based on the results of the MTBDRplus assay in patients with pulmonary tuberculosis (PTB). This prospective, multicenter noninferiority randomized trial was conducted at 12 referral centers in South Korea in drug-susceptible PTB patients who initiated the standard four-drug regimen for PTB. Based on the results of the assay, EMB was discontinued in the MTBDRplus group after confirmation that the M. tuberculosis isolate was susceptible to isoniazid and rifampin. The time point for EMB discontinuation in the guideline group was determined using the results of the phenotypic drug susceptibility test based on the South Korean national tuberculosis guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Of 600 randomized patients, the treatment outcome analysis was performed for 493 patients (MTBDRplus group, 244 patients; guideline group, 249 patients). Treatment success rates were 93.9% (229/244) in the MTBDRplus group and 93.6% (233/249) in the guideline group and did not differ between groups (relative risk, 1.00; 95% confidence interval, 0.95 to 1.06). The 1-year recurrence rates in the two groups (0.9% and 0.5%, respectively) and adverse drug reactions did not differ between the groups. In conclusion, the early discontinuation of EMB based on the results of the MTBDRplus assay did not affect the treatment outcomes in patients with PTB. (This clinical trial has been registered with the Clinical Research Information Service of the Republic of Korea [https://cris.nih.go.kr/cris/] under registration no. KCT0000610.)