In Vitro Activities of Linezolid against Multiple Nocardia Species

Abstract

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 ...

Clinical and Laboratory Features of theNocardiaspp. Based on Current Molecular Taxonomy

“…Linezolid, the first agent in this class to be studied against Nocardia, showed extraordinary in vitro activity against all of the major clinically significant species of Nocardia. The MIC 90 for linezolid was Յ4 g/ml against isolates of N. asteroides, N. farcinica, N. nova, N. brasiliensis, N. pseudobrasiliensis, the N. transvalensis complex, and N. otitidiscaviarum (27). Thus, it is the first antimicrobial agent other than the sulfonamides to be active against most or all isolates of all pathogenic species of Nocardia.…”

Nocardia cyriacigeorgica Septicemia

“…Both of our N. cyriacigeorgica strains demonstrated in vitro susceptibility to TMP-SMX, imipenem, and amikacin. Linezolid appears to be the most effective agent against Nocardia species based on in vitro data, although experience with this drug in the treatment of Nocardia infections is limited (4,5). In summary, N. cyriacigeorgica represents a distinct lineage within the genus Nocardia that is now believed to be identical to formerly uncategorized strains within this genus.…”

Pulmonary Nocardiosis with Brain Abscess in a Sensitized Kidney Transplant Recipient with a History of Repeated Graft Loss and HLA-Antibody Depletion Treatment – A case report

“…Final choice of antibiotic treatment is, however, dependent on the susceptibility testing, since some strains of Nocardia such as N. nova, N. otitidiscaviarum and especially N. farcinica may have high-grade resistance to sulfamethoxazole (10). In cases of sulfamethoxazole resistance linezolid is the agent of choice, since it is effective against all species of Nocardia including N. facinica (11). Prolonged linezolid treatment can, however, be limited by serious myelosuppression, including neutropenia, thrombocytopenia and anemia (12).…”