Tuberculosis (TB) is an important public health problem and remains one of the most threatening curable infectious diseases, despite improvements in diagnostic and drug susceptibility tests. The effective control of TB is based on the immediate detection of Mycobacterium tuberculosis, followed by the prompt implementation of adequate antituberculous therapy (29).The emergence of strains resistant to the major anti-TB drugs speeds up the need for rapid methods for the identification of resistant M. tuberculosis strains in order to treat the disease effectively and, at the same time, prevent the spread of resistant strains (6,8,9,16). Multidrug-resistant (MDR) M. tuberculosis strains, which are resistant at least to rifampin (RIF) and isoniazid (INH), have emerged worldwide and seriously threaten TB control and prevention programs (30).The main mutations that confer RIF resistance are located in the rpoB gene, specifically, in the well-defined 81-bp core region (22,24). About 95% of RIF-resistant strains have a mutation in this region, which facilitates the rapid development of approaches for the detection of resistance to this drug (23,24,26). However, the molecular basis of resistance to

The purpose of this study was to evaluate the GenoType MTBDRsl assay (Hain Lifescience GmbH, Nehren, Germany) for its ability to detect resistance to fluoroquinolones (FLQ), injectable second-line antibiotics [kanamycin (KM) and capreomycin (CM)], and ethambutol (EMB) in Mycobacterium tuberculosis clinical strains and directly in clinical samples. A total of 34 clinical strains were characterized with the Bactec 460 TB system. Fifty-four clinical samples from 16 patients (5 were smear negative and 49 were smear positive) were also tested directly. The corresponding isolates of the clinical specimens were also analyzed with the Bactec 460TB. When there was a discrepancy between assays, pyrosequencing was performed. The overall rates of concordance of the MTBDRsl and the Bactec 460TB for the detection of FLQ, KM/CM, and EMB susceptibility in clinical strains were 72.4% (21/29), 88.8% (24/27), and 67.6% (23/34), whereas for clinical samples, rates were 86.5% (45/52), 92.3% (48/52), and 56% (28/50), respectively. In conclusion, the GenoType MTBDRsl assay may be a useful tool for making early decisions regarding KM/CM susceptibility and to a lesser extent regarding FLQ and EMB susceptibility. The test is able to detect mutations in both clinical strains and samples with a short turnaround time. However, for correct management of patients with extensively drugresistant tuberculosis, results must be confirmed by a phenotypical method. E fficient tuberculosis (TB) control is based on an early diagnosis followed by the rapid identification of drug resistance, in order to treat patients adequately, break the chain of transmission, and avoid the spread of resistant strains (38). Multidrug-resistant (MDR) Mycobacterium tuberculosis strains resistant at least to isoniazid (INH) and rifampin (RIF), which are two of the main firstline anti-TB drugs, have emerged worldwide and seriously threaten TB control and prevention programs. At the same time, the emergence of extensively drug-resistant tuberculosis (XDR TB), defined as MDR TB with additional resistance to fluoroquinolones (FLQ) [moxifloxacin (MOX), ofloxacin (OFL), and levofloxacin] and at least one of the three injectable second-line drugs [amikacin (AM), kanamycin (KM), and capreomycin (CM)], has also become an important global health problem.Conventional methods for detecting XDR strains are sequential, because they are applied once a strain has grown in solid or liquid medium and has been shown to be resistant to first-line drugs, mainly RIF and INH. As a consequence, the pattern of resistance to second-line drugs becomes available later. In addition, methods of detecting resistance to second-line drugs are not fully standardized (19,39), so the comparison of resistance incidences between different geographical settings is difficult.Regarding first-line drugs, mutations related to INH and RIF resistance have been extensively investigated and involve mainly the rpoB, katG, and inhA genes (30). Ethambutol (EMB) is another first-line drug, and its resistance has been rel...

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