An in vitro time-kill assessment of linezolid and anaerobic bacteria

Linezolid is a novel oxazolidinone antibacterial agent active against staphylococci (including methicillin-resistant strains), enterococci (including vancomycin-resistant strains), streptococci (including penicillin-intermediate and -resistant Streptococcus pneumoniae), and other aerobic and facultative bacteria. The agent has also demonstrated activity against a broad spectrum of Gram-positive and Gram-negative anaerobic bacteria. Previous time-kill assessments have shown linezolid to be generally bacteriostatic against staphylococci and enterococci, and bactericidal against streptococci. In this study, an anaerobic glovebox technique was employed to conduct time-kill assessments for four strains of anaerobic Gram-positive, and seven strains of anaerobic Gram-negative bacteria. The time-kill experiment was performed using Anaerobe Broth medium. The drugs were tested at four-fold the minimum inhibitory concentration (MIC), or at the higher concentration of 8 mg/L for linezolid, 2 mg/L for clindamycin, and 8 mg/L for metronidazole. Samples for viable count were taken at 0, 6, and 24 h, and plated using the Bioscience International Autospiral DW. Exposure of samples to the aerobic environment during plating was held to less than 30 min. Plates were counted after a 48 h anaerobic incubation (37degreesC). The species tested included Bacteroides fragilis (2), B. distasonis, B. thetaiolaomicron, Fusobacterium nucleatum, F varium, Prevotella melaninogenica, Clostridium perfringens, Eubacterium lentum and Peptostreptococcus anaerobius (2). The activity of linezolid was compared to that of metronidazole and clindamycin, two standard anti-anacrobe agents. As expected. the control agents were very active in these assays. Metronidazole yielded log(10) CFU/mL reductions of 3.0 or greater for nine of ten strains; clindamycin yielded log(10) CFU/mL reductions of 2.0 or greater for six of I I strains, and 3.0 or greater for three strains. Linezolid also produced significant in vitro killing in this model achieving log(10) CFU/mL reductions of 2.0 or greater for six of I I strains, and 3.0 or greater for four strains. The profile of activity was similar to that of clindamycin indicating that additional developmental studies of linezolid with anaerobic bacteria are warranted. (C) 2003 Elsevier Science Ltd. All rights reserved.