Objectives:

Linezolid is an oxazolidinone antimicrobial with established in vitro and in vivo activity against aerobic Gram-positive cocci. In infections such as wounds these Gram-positive pathogens may be mixed with other pathogens including anaerobes. The role of linezolid as an anti-anaerobe agent has yet to be determined. This study was performed to establish the in vitro activity of linezolid and comparative agents against recently isolated anaerobes.

Methods:

Approximately 700 anaerobes were tested for susceptibility to linezolid (LZD), ceftriaxone (AXO), cefoxitin (FOX), clindamycin (CL), and metronidazole (MRD) using twofold dilutions (0.06–256 mg/L) of each agent using the NCCLS-recommended broth microdilution method. The sources of test isolates included wounds, abscesses, body fluids, and tissues.

Results:

Against all test isolates LZD had an MIC range of 0.06–128 mg/L, a mode MIC of 4 mg/L, and MIC50 and MIC90 values of 2 and 4 mg/L, respectively. LZD activity was judged by percentage of isolates inhibited at 2 and 4 mg/L. Overall LZD inhibited 51 and 96% of isolates at 2 and 4 mg/L, respectively; at 2 and 4 mg/L, respectively, LZD inhibited 35 and 95% of Bacteroides fragilis group; 63 and 92% of Clostridium isolates; 71 and 97% of Prevotella isolates; 100% of Fusobacterium isolates; and 100% of Peptostreptococcus isolates. By comparison of MIC90 values LZD was 2- to 64-fold more active than AXO, 0- to 16-fold more active than FOX, and 2- to 32-fold more active than CL against these same groups of isolates. LZD and MRD had virtually equal in vitro activity. Interestingly, all isolates with MICs of 8 mg/L or higher to LZD had MICs of 2 mg/L or less to MRD, while isolates with MICs of 8 mg/L or higher to MRD had MICs of 4 mg/L or less to LZD.

Conclusions:

Based on these results and arbitrary use of NCCLS breakpoints for Gram-positive isolates, we conclude that LZD is highly active against anaerobe pathogens, but this needs to be verified by pharmacokinetic and clinical studies.