In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp

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Abstract
Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca 2+ to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC 90 s) for telavancin and vancomycin were as follows: Actinomyces spp. ( n = 45), 0.25 and 1 μg/ml, respectively; Clostridium difficile ( n = 14), 0.25 and 1μ g/ml, respectively; Clostridium ramosum ( n = 16), 1 and 4 μg/ml, respectively; Clostridium innocuum ( n = 15), 4 and 16 μg/ml, respectively; Clostridium clostridioforme ( n = 15), 8 and 1 μg/ml, respectively; Eubacterium group ( n = 33), 0.25 and 2μ g/ml, respectively; Lactobacillus spp. ( n = 26), 0.5 and 4 μg/ml, respectively; Propionibacterium spp. ( n = 34), 0.125 and 0.5 μg/ml, respectively; Peptostreptococcus spp. ( n = 52), 0.125 and 0.5 μg/ml, respectively; and Corynebacterium spp. ( n = 31), 0.03 and 0.5 μg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei , where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 μg/ml) against 14 strains of Actinomyces spp. and all C. ramosum , Eubacterium lentum , and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 μg/ml) against C. ramosum , two strains of C. difficile , and 15 strains of Lactobacillus spp. Imipenem and piperacillin-tazobactam were active against >98% of strains. The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei were >1 μg/ml. The MIC 90 of TD-6424 for all strains tested was ≤2 μg/ml. TD-6424 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.