[Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in dermal interstitial 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 activity at the site of skin infections.


METHODS
This comparative open study was conducted in 12 healthy volunteers using a repeated latin square experimental scheme. Antibiotic concentrations in serum and suction bullae fluid were measured by high performance liquid chromatography after 5.5 days of repeated oral administration of fusidic acid (1 g/d), oxacillin (2 g/d), and pristinamycin (2 g/d).


RESULTS
Mean antibiotic concentrations in serum and interstitial fluid (suction bullae fluid) were highest for fusidic acid with a Cmax at 91.3 +/- 23.0 mg/l and 45.5 +/- 18.0 mg/l respectively (interstitial fluid/serum ratio=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 concentration-time curves showed that the best diffusion was obtained with pristinamycin (114 +/- 61 p. 100), followed by fusidic acid (57 +/- 13 p. 100) and oxacillin (48 +/- 25 p. 100).


CONCLUSIONS
These data were used to calculate indicators of potential efficacy in the interstitial dermal fluid: inhibitor quotient (Cmax/MIC) and AUIC (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 streptococci, the observed interstitial concentrations of pristinamycin and of fusidic acid should theoretically inhibit streptococci A growth, but oxacillin was the most adapted antibiotic.
Vaillant
L
L
Service de Dermatologie, CHU Trousseau, 37044 Tours Cedex 1.
Le Guellec
C
C
Jehl
F
F
Barruet
R
R
Sorensen
H
H
Roiron
R
R
Autret-Leca
E
E
Lorette
G
G
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D005110:Extracellular Space / Q000378:metabolism*; D005672:Fusidic Acid / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010068:Oxacillin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D010406:Penicillins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D014769:Virginiamycin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D010406:Penicillins; D014769:Virginiamycin; D005672:Fusidic Acid; D010068:Oxacillin