Linezolid is an oxazolidinone available as an oral drug which has activity against most gram-positive bacteria. However, few species of the genus Mycobacterium have been studied. We tested 249 clinical isolates and 10 reference strains of rapidly growing mycobacteria for susceptibility to linezolid by broth microdilution. Clinical species included the Mycobacterium fortuitum group (n ‫؍‬ 74), M. abscessus (n ‫؍‬ 98), M. chelonae (n ‫؍‬ 50), M. mucogenicum (n ‫؍‬ 10), and M. fortuitum third biovariant complex (10). The modal MIC for M. mucogenicum was 1.0 g/ml, and the MIC at which 90% of the isolates tested are inhibited (MIC 90 ) was 4 g/ml; the modal MIC for the M. fortuitum group was 4 g/ml, and the MIC 90 was 16 g/ml; the modal MIC for the M. fortuitum third biovariant complex was 4 g/ml, and the MIC 90 was 8 g/ml; the modal MIC for M. chelonae was 8 g/ml, and the MIC 90 was 16 g/ml; and the modal MIC for M. abscessus was 32 g/ml, and the MIC 90 was 64 g/ml. Based on peak levels of linezolid in serum of 15 to 20 g/ml, we propose the following broth MIC breakpoints for these species: susceptible, < 8 g/ml; moderately susceptible, 16 g/ml; and resistant, >32 g/ml). These studies demonstrate the excellent potential of linezolid for therapy of rapidly growing mycobacteria.Treatment of infections due to nontuberculous mycobacteria remains difficult, in part because they are resistant to many of the first-line tuberculosis agents and in part because so few other agents are available for therapy (21 , abstr. 1098, 1999) which have the potential for activity against nontuberculous mycobacteria, including the rapidly growing mycobacteria (6; M. Wu, P. Aralor, K. Nash, L. E. Bermudez, C. B. Inderlied, and L. S. Young, Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. E-143, 1998; L. E. Bermudez, Abstr. Int. Conf. Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinone, abstr. 03.16, 2000).We chose to study linezolid, which along with eperezolid is the first of the oxazolidinones to reach clinical testing (4; M. C. Birmingham et al., 39th ICAAC) Linezolid offers special promise, as it is a twice-daily oral drug which is 100% bioavailable (Zyvox package insert, 2000 [Pharmacia & Upjohn, Inc.]; also see reference 8) and appears to be well tolerated (8; N. E. Wilks, Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1763Chemother., abstr. , 1999, important features of therapeutic drugs to be used against nontuberculous mycobacteria which cause chronic infections and require long-term therapy (often 6 months or longer) (21). The activities of linezolid against a large number of clinical isolates of rapidly growing mycobacteria, including the common disease-producing species Mycobacterium fortuitum, M. chelonae, and M. abscessus (24), were studied.(This work was presented in part as an abstract at the 100th General Meeting of the American Society for Microbiology, Los Angeles, Calif.) T , and M. abscessus ATCC 19977 T . Susceptibility testing. Susceptibility testing utilized seri...

Linezolid was tested by broth microdilution against 140 clinical Nocardia isolates belonging to seven species. The MIC at which 50% of the strains are inhibited (MIC 50 ) and MIC 90 for all species other than Nocardia farcinica were 2 and 4 g/ml. Linezolid is the first antimicrobial agent demonstrated to be active against all Nocardia species.Treatment of Nocardia infections continues to be difficult, especially with central nervous system or disseminated disease (1,6,7,9,10) and species, such as Nocardia farcinica, that are highly drug resistant (22). Most recent antimicrobial therapy of complicated cases has involved the use of a sulfonamide or trimethoprim-sulfamethoxazole plus the injectable agents amikacin and imipenem or ceftriaxone (6,10,16,18 E-143, 1998.). We studied the new oxazolidinone compound linezolid against all clinically important species of Nocardia including drug-resistant species, such as N. farcinica and Nocardia transvalensis (22,23).(Presented in part at the 99th Annual Meeting of the American Society for Microbiology, Los Angeles, Calif., May 2000.)Linezolid is a new class of synthetic antibiotics which prevent protein synthesis by blocking the formation of a function initiation complex (9, 11). The exact mechanism of action is unique, and no cross-resistance has been discovered in strains of bacteria resistant to other antimicrobial agents (11).We tested 192 clinical Nocardia isolates submitted for susceptibility testing from January 1999 through January 2000 to the Mycobacteria/Nocardia Research Laboratory at The University of Texas Health Center for their susceptibility to linezolid. Isolates from 27 states and Mexico were tested, with 60% of the isolates from Texas, Florida, North Carolina, Ohio, Massachusetts, and Connecticut. Approximately 40% of the organisms were identified to the species level by PCR restriction analysis of the 439-bp Telenti segment of the 65-kDa hsp gene (13)(14)(15)(16)23), and all were identified by their patterns of susceptibility (16,17,(20)(21)(22)(23) to approximately 15 other drugs, including aminoglycosides, beta lactams, and quinolones. The test isolates belonged to seven species (eight taxa) and included Nocardia asteroides sensu stricto (n, 34), N. farcinica (n, 25), Nocardia brasiliensis (n, 24), Nocardia nova (n, 41), Nocardia pseudobrasiliensis (n, 8), Nocardia otitidiscaviarum (n, 5), N. transvalensis complex (n, 7), and Nocardia sp. (n, 2).Susceptibility testing utilized three methods. The first was serial twofold broth microdilution in cation-supplemented Mueller-Hinton broth as previously described and recently approved by the NCCLS (4, 24). The second was the E-test (2) (generously supplied by Pharmacia and Upjohn, Inc., and AB Biodisks) performed on selected isolates on Mueller-Hinton agar using a 1-McFarland standard inoculum. The third method was agar disk diffusion (20, 21) performed with Mueller-Hinton agar and 30-g linezolid disks generously supplied by the manufacturer, Pharmacia and Upjohn, Inc. Susceptibilities to linezolid by all ...