The antibacterial activity of telavancin and vancomycin against UK EMRSA 15 and 16 strains studied in an in vitro pharmacokinetic model

Abstract number: P1051

Noel A., Bowker K., Tomaselli S., MacGowan A.

Objective: Telavancin (tela) is an injectable new semi synthetic lipoglycopeptide antibiotic with broad activity against Gram-positive pathogens including MRSA. It has a double mechanism of action on the cell membrane and wall resulting in bactericidal activity. We used an in vitro pharmacokinetic (pK) model to simulate serum free drug concentrations of tela and vancomycin (vanco), and studied their antibacterial effect against representative strains of UK EMRSA 15 and 16.

Methods: A single chamber dilutional in vitro pK model was used to simulate serum free drug concentrations. Tela Cmax 10 mg/L, t½ 8 hr, 2 doses over 48 h; vanco Cmax 14 mg/L, Cmin 3.5 mg/L, 4 doses over 48 h. Two strains of UK EMRSA 15 and 16 were used (both tela MIC 0.19 mg/L). Experiments were performed in triplicate at an initial inoculum of 10^6 CFU/ml. Antibacterial effect was measured by log change in viable count at 6 h (d6), 12 h (d12), 24 h (d24) and 48 h (d48). The maximum kill was recorded (dmax) and the area-under-the-bacterial-kill curve between 0–24 h (AUBKC24) and 0–48 h (AUBKC48) calculated.

Results: The killing kinetics of both strains were similar, therefore the antibacterial effect measures were pooled for tela and vanco, and compared.

Conclusion: Tela produced significantly greater early killing of EMRSA 15 and 16 than vancomycin (d6, d12). The maximum kill was also greater (dmax) as was the antibacterial effect in the first 24 h (AUBKC24).