1: J Antimicrob Chemother. (2006) 58, 1177–1184 Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. Barcia-Macay M, Lemaire S, Mingeot-Leclercq MP, Tulkens PM, Van Bambeke F. Unite de Pharmacologie cellulaire et moleculaire, Universite catholique de Louvain, B-1200 Brussels, Belgium. OBJECTIVES: To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA). METHODS: Determination of cfu changes (3-24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000x MIC. RESULTS: Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration-effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3-1x MIC and 100-1000x MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [-3 log (MSSA) to -1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. -0.5 log decrease at 24 h and at Cmax). CONCLUSIONS: Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin. PMID: 17062609 [PubMed - as supplied by publisher] Related Links Efficacy of Telavancin in a rabbit model of aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus or vancomycin-intermediate Staphylococcus aureus. [Antimicrob Agents Chemother. 2005] PMID:16048918 Pharmacodynamics of telavancin (TD-6424), a novel bactericidal agent, against gram-positive bacteria. [Antimicrob Agents Chemother. 2004] PMID:15273119 Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus. [J Antimicrob Chemother. 2006] PMID:16787952 Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model. [Antimicrob Agents Chemother. 2004] PMID:15561842 Telavancin versus standard therapy for treatment of complicated skin and soft-tissue infections due to gram-positive bacteria. [Clin Infect Dis. 2005] PMID:15889357