Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections

Abstract

Linezolid soft tissue penetration and serum antimicrobial activity were analysed in six patients with peripheral vascular disease and severe diabetic foot infections requiring surgical intervention. Blood draws (1, 3, 6, 9 and 12 h after initiation of a 1 h infusion) and a viable soft tissue sample at the site of infection were obtained in patients receiving linezolid (600 mg every 12 h) on the day of surgery. Concentrations of linezolid were determined by HPLC in both tissue (pre-treated with tissue lysis buffer) and serum. In addition, serum inhibitory and bactericidal activity (dilution titres 1:2-1:32) of linezolid was determined in these patients against strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (vancomycin MICs = 2, 4, 8, 256 and >256 mg/L). Linezolid concentrations in tissue were found to be 51% (range, 18% to 78%) of simultaneous serum concentrations. Rapid (1 h) and prolonged (12 h) inhibitory activity (titres > or = 1:2) was observed for linezolid against each of the study isolates. Furthermore, bactericidal activity (titres > or = 1:2) was observed for at least 6 h (50% of the dosing interval) against four of these five strains. These findings suggest that linezolid could be effective in the treatment of multidrug-resistant MRSA even when concentrations at the infection site are diminished due to impaired blood flow.