[Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in dermal interstitial fluid after repeated oral administration]. / Diffusions comparées de l'acide fusidique, de l'oxacilline et de la pristinamycine dans le liquide interstitiel dermique après administration orale répétée.

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. SUBJECTS AND 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). DISCUSSION: 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.

In vitro activity of fusidic acid against streptococci isolated from skin and soft tissue infections.

The in vitro activity of fusidic acid was evaluated against 242 strains of streptococci isolated from skin and soft tissue infections during a prospective multicentre study. Nearly 90% of strains were isolated from dermatology, emergency and medicine units. Groups A, B, C and G streptococci represented, respectively, 41.9, 20.6, 4.4 and 27.8% of the strains. The activity of fusidic acid was dependent on the media used. MICs were generally one dilution lower with heart infusion agar than with Mueller-Hinton agar supplemented with 5% horse blood (MIC(90) for the whole streptococcal population = 8 mg/L and 16 mg/L, respectively). The distribution of MICs was unimodal and only two strains displayed MICs of fusidic acid >/= 64 mg/L. In both media, fusidic acid was moderately active against streptococci. However, antibiotic concentrations obtained in the skin exceed the MIC(90) of fusidic acid for streptococci, possibly explaining its clinical efficacy in the treatment of common cutaneous infections.

Oral treatment of Staphylococcus spp. infected orthopaedic implants with fusidic acid or ofloxacin in combination with rifampicin.

Oral therapy of staphylococcal infection of orthopaedic implants with 900 mg/day rifampicin combined with either 1.5 g/day fusidic acid for 5 days followed by 1 g/day thereafter, or 600 mg/day ofloxacin was compared. Patients with an infected hip were treated for 6 months, with removal of any unstable prosthesis after 5 months' treatment and those with an infected knee prosthesis were treated for 9 months, with removal of the prosthesis after 6 months of treatment. Patients with infections of other type of bone implants were treated for 6 months with removal of the implant after 3 months of treatment, if necessary. Cure was defined as the absence of clinical, microbiological and radiological evidence of infection 12 months after completion of treatment. The treatment of 46 of the 52 included in the study was evaluated for safety and that of 42 was assessed for efficacy. Overall treatment was successful for 11 (55%) of 20 patients treated with rifampicin and fusidic acid group and for 11 (50%) of the 22 treated with rifampicin and ofloxacin. Treatment failed in four cases in each treatment group because of persistent infection. One patient given rifampicin and fusidic acid and three patients given rifampicin and ofloxacin failed treatment because of relapse. Superinfection led to failure in the remainder and was due to staphylococci in all but one case in which Acinetobacter calcoaceticus var. anitratus was isolated. There were no side effects related to study treatment. Oral treatment with rifampicin combined with fusidic acid may be a suitable alternative to the combination of rifampicin and ofloxacin for treating implant infections due to Staphylococcus spp. either when the patient is intolerant to quinolones or when the infecting organism is resistant to these drugs.

Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension.

The pharmacokinetics of fusidic acid (Fucidine, Leo Laboratories) were studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml). Nine blood samples were drawn from each child at 0, 1, 2, 3, 6, 8, 12, 24 and 48 h following dosing with the antibiotic. Serum fusidic acid levels were measured by high-performance liquid chromatography (HPLC). A model-independent method was used for the pharmacokinetic analysis. Results were compared with those obtained after dosing eight healthy adult volunteers with 500 mg of sodium fusidate by parenteral administration (infusion) then per os. The acceptability of the single dose was good. The terminal elimination half-life t1/2 (h) and the mean residence time (MRT, h) of fusidate were similar to those determined in healthy adults after oral dosing, i.e. 16.0 +/- 14.5 versus 16.0 +/- 3.5 and 17.7 +/- 12.1 versus 17.7 +/- 2.5, respectively. In contrast, the oral bioavailability of the suspension (Fapprox., %) was relatively low: of the order of 22.5 versus 91.0% for tablets in the healthy adult, which justifies the use of a relatively higher dose in the child. This led to the calculation of an estimated total clearance (Clest., ml/min) significantly less than that in the healthy adults, while the estimated apparent volume of distribution (Vd, litre/kg) was significantly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0.53 versus 0.30 +/- 0.04, respectively). Fusidic acid is normally excreted in metabolized form (98%). The decrease in clearance could be attributed to the almost immediate saturation of liver enzymes in immature infants.(ABSTRACT TRUNCATED AT 250 WORDS)