In this multicenter study, the reliability of two nonradiometric, fully automated systems, the MB/BacT and BACTEC MGIT 960 systems, for testing the susceptibilities of 82 Mycobacterium tuberculosis strains to isoniazid, rifampin, ethambutol, and streptomycin was evaluated in comparison with the radiometric BACTEC 460TB system. The arbitration of discrepant results was done by the reanalysis of the strain, the determination of the MIC, and the molecular characterization of some resistance determinants. The overall level of agreement with BACTEC 460TB results was 96% with the MB/BacT test and 97.2% with the BACTEC MGIT 960 system. With both methods, the level of agreement with BACTEC 460TB results was 96.3% for isoniazid, 98.8% for rifampin, and 98.8% for ethambutol. The level of agreement for streptomycin was 90.2% with MB/BacT and 97.5% with BACTEC MGIT 960. Overall, there were 11 very major errors and 2 major errors with the MB/BacT method and 5 very major errors and 2 major errors with the BACTEC MGIT 960 system. In general, the MB/BacT and BACTEC MGIT 960 systems showed good performance for susceptibility testing with first-line antituberculosis drugs.Tuberculosis (TB) is one of the most prevalent infectious diseases in the world. According to a recent report of the World Health Organization, in 2003 there were 8.8 million new TB cases and around 1.7 million deaths attributable to the disease (25). In addition, multidrug-resistant TB is becoming increasingly common and is a major health concern in many regions of the world, particularly in developing nations (24). Rapid, accurate diagnosis and the determination of drug susceptibility are crucial to optimize treatment and prevent transmission. The most widely used method for Mycobacterium tuberculosis drug susceptibility testing is the proportion method, either on solid medium or on liquid broth. The BACTEC 460TB system (Becton Dickinson Biosciences, Sparks, MD) has been widely validated for approximately 20 years for the reliable and rapid testing of the susceptibilities of M. tuberculosis isolates (9, 16, 21). The radiometric BACTEC 460TB test requires fewer than 14 days of incubation before results are available, but it is semiautomated and entails the disposal of a radioactive substance (16).New liquid medium-based systems have recently been introduced for the nonradiometric susceptibility testing of M. tuberculosis (4, 10, 17-19). These include the ESP Culture System II (AccuMed International, Westlake, OH), the MB Redox system (Biotest, Dreieich, Germany), the BACTEC MGIT 960 mycobacterial growth indicator tube system (Becton Dickinson Microbiology Systems, Sparks, MD), and the MB/BacT system (bioMérieux, Marcy l'Etoile, France).In the present multicenter study, we evaluated the reliability of the MB/BacT and BACTEC MGIT 960 systems for testing M. tuberculosis susceptibility to streptomycin, isoniazid, rifampin, and ethambutol (a combination known as SIRE) and compared the results obtained with these methods to those obtained with the radiometric BACTEC ...