Title

Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

Document Type

Article

Publication Date

4-1-2013

DOI

https://doi.org/10.1128/AAC.02127-12

Abstract

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin susceptible S. aureus (MSSA), 10 methicillin resistant S. aureus (MRSA), and 10 heterogeneously vancomycin intermediate S. aureus (hVISA) were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of telavancin 10 mg/kg once daily alone and combined with nafcillin 2 g every 4 h, imipenem 500 mg every 6 h, or gentamicin 5 mg/kg once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin + nafcillin, and 63% with telavancin + imipenem. In the PK/PD model against MRSA and hVISA all three combinations were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). Against MSSA all three combinations were generally similar to each other except one strain where telavancin + imipenem was superior to all other regimens (P ≤ 0.011). The combination of telavancin and beta-lactam agents was similar in activity compared to telavancin + gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin + gentamicin, these beta-lactam combinations may have clinical utility.

Comments

This article was created while Prof. Steven Leonard was part of Northeastern University's Bouvé College of Health Sciences, School of Pharmacy, in Boston, Massachusetts.

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