Effects of Vancomycin Subtherapeutic Concentration on Staphylococcus aureus Isolated from Hemodialysis Patients with Low Serum Trough Concentrations.

Abstract

Blood bactericidal activity and antimicrobial therapy are crucial against catheter-related infection in patients undergoing hemodialysis (HD). It is well-known that catheters colonized by biofilm-producing bacteria are a risk factor for bacteremia in HD-patients. Methicillin-resistant S. aureus bacteremia in HD-patients justify the use of vancomycin as empiric therapy. The recommended vancomycin target for therapeutic efficacy is a minimum serum concentration of 10µgmL-1 to avoid resistance. However, subtherapeutic concentrations of vancomycin have frequently occurred in HD-patients. Thus, we aim to investigate the effect of subtherapeutic vancomycin concentration on S. aureus growth, susceptibility to antimicrobials, resistance to whole blood activity, and biofilm formation. Seventeen S. aureus strains isolated from bacteremia in HD-patients and two reference strains were exposed to a vancomycin-gradient (0-10µgmL-1) for five consecutive days to mimic the dosing interval of vancomycin in HD-patients. After that, we observed the following: no effect on growth curve; decreased susceptibility to vancomycin and daptomycin; increased S. aureus survival to whole blood bactericidal action; and a strain-dependent biofilm production after drug exposure. In conclusion, our findings suggest that the subtherapeutic concentration of vancomycin decrease S. aureus susceptibility to vancomycin and daptomycin and increases its survival to whole blood bactericidal action.