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]

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