Efficacy of fosfomycin + vancomycin or gentamicin in experimental endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA).
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Biomedical subjects
Publications and source records attributed to M V Vicente.
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The efficacy of fosfomycin in combination with vancomycin or gentamicin was evaluated in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus. After 5 days of therapy, both combinations proved to be highly effective since all rabbits had sterile vegetations.
The penetration of N-formimidoyl thienamycin into extravascular fluids was studied in rabbits. Two different models were used: subcutaneously implanted tissue chambers and fibrin clots. The antibiotic was given intramuscularly as a single dose of 10 mg/kg. The degree of penetration into these compartments was determined by comparing the area under the curve for the specific fluid with the area under the curve for plasma expressed in percent. The percentage of penetration of N-formimidoyl thienamycin into tissue chamber fluid (76.24%) was similar to that into fibrin clots (75.15%).
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The effectiveness of fosfomycin in combination with other antibiotics was studied in vitro and in the treatment of left-sided endocarditis in rabbits caused by S. sanguis, S. faecalis, S. aureus or P. aeruginosa. In vitro combinations of fosfomycin plus penicillin, fosfomycin plus cloxacillin, and fosfomycin plus amikacin were synergistic against the strains tested. In vivo synergism was also demonstrated since fosfomycin combinations produced a greater reduction in the number of CFU/g of vegetations than the administration of one antibiotic alone.
The effectiveness of penicillin G, fosfomycin, and cefoxitin alone and in combination was studied in vitro and in the treatment of left-sided Streptococcus sanguis endocarditis in rabbits. In vitro, the combinations penicillin G plus fosfomycin, penicillin G plus cefoxitin, and fosfomycin plus cefoxitin were synergistic or partially synergistic for S sanguis. Therapy with the combinations was more effective in eradicating the species from cardiac vegetations that was that with each antibiotic used alone.
The ability of seven antibiotics (carbenicillin, cloxacillin, ampicillin, cephalothin, cephaloridine, cefoxitin and fosfomycin) to enter interstitial tissue fluid was evaluated. Using rabbits with implanted subcutaneous chambers, antibiotics were given intramuscularly as a single dose of 15 mg/kg, and antibiotic levels in serum and interstitial fluid of the chambers were determined at variously scheduled times after injection. The results indicated that antibiotic concentrations in the two compartments did not run parallel. The pharmacokinetic analysis showed that, in general, antibiotic diffusion from blood to interstitial fluid increased with the concentration gradient and the serum half-life, and there was an inverse relationship to pKa, protein binding and molecular weight of the antibiotic.
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