Activities of Linezolid against Rapidly Growing Mycobacteria

Abstract

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: The First Oxazolidinone Antimicrobial

“…Linezolid has good activity against many gram-positive anaerobes; its activity against Bacteroides fragilis is borderline (minimum inhibitory concentration of 4 g/mL for 50% of strains), but it is bactericidal against these organisms (8). Of interest, linezolid exhibits relatively good in vitro activity against many strains of Mycobacterium tuberculosis (8) and has activity against the Mycobacterium avium complex and several rapidly growing mycobacteria, including Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus (14,15). The clinical significance of the activity of linezolid against mycobacteria is not known, but, of interest, it is possible to produce oxazolidinone derivatives with even greater activity against mycobacteria (16).…”

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus

“…Furthermore, we investigated whether LCB01-0371 had the same molecular target as the other compounds of the oxazolidinone class, such as linezolid and sutezolid (PNU-100480). Linezolid binds to the 23S subunit of the bacterial ribosome to prevent protein synthesis; in vitro testing indicated that M. abscessus was susceptible to linezolid (26). As seen in Fig.…”

Sensibilidad a los antimicrobianos de micobacterias de crecimiento rápido mediante el método E-test

“…La actividad in vitro de estos fármacos parece ser buena pero la experiencia clínica aún es limitada. Según nuestros resultados, tigeciclina presenta una excelente actividad para todas las especies de MCR; linezolid es efectivo frente a M chelonae, pero algo menos frente a M fortuitum y M abscessus; en el caso de quinupristina/dalfopristina, se puede decir que es ineficaz frente a la mayoría de las especies de MCR 12,18,[22][23][24] .…”