Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in interstitial dermal fluid after repeated oral administration.

Objective, The aim of this study was to use the suction bullae technique to compare skin diffusion of 3 antibiotics commonly used for skin infections (fusidic acid, oxacillin, pristinamycin) and to estimate their potential ac tivity at the site of skin infections. Subjects and methods. This comparative open study was conducted in 12 healt hy volunteers using a repeated latin square experimental scheme. Antibiotic concentrations in serum and suction bullae fluid were measured by high per formance liquid chromatography after 5.5 days of repeated oral administrati on of fusidic acid (1 g/d), oxacillin (2 g/d), and pristinamycin (2 g/d). Results. Mean antibiotic concentrations in serum and interstitial fluid (su ction bullae fluid) were highest for fusidic acid with a Cmax at 91.3 +/- 2 3.0 mg/l and 45.5 +/- 18.0 mg/l respectively (interstitial fluid/serum rati o = 49 +/- 10 p. 100). For oxacillin, Cmax was 8.3 +/- 3.6 mg/l and 0.98 +/ - 0.49 mg/l (ratio 13 +/- 5 p. 100). Pristinamycin concentrations were low with a Cmax at 0.51 +/- 0.40 and 0.26 +/- 0.15 mg/l (ratio 73 +/- 57 p. 100 ). Comparing the area under the interstitial fluid and the serum concentrat ion-time curves showed that the best diffusion was obtained with pristinamy cin (114 +/- 61 p. 100), followed by fusidic acid (57 +/- 13 p. 100) and ox acillin (48 +/- 25 p. 100). Discussion. These data were used to calculate indicators of potential effic acy in the interstitial dermal fluid: inhibitor quotient (Cmax/MIC) and AUI C (ASC/MIC), indicator of the time antibiotic concentrations are maintained above the minimal inhibitor concentration (MIC). This showed that fusidic acid was potentially more active against all staphylococci. For streptococc i, the observed interstitial concentrations of pristinamycin and of fusidic acid should theoretically inhibit streptococci A growth, but oxacillin was the most adapted antibiotic.