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V. Petternel, K. Krepler, J. Schauersberger, A. Wedrich; Fosfomycin in human vitreous: –In–vitro investigation of the protein binding of fosfomycin in human vitreous –Fosfomycin levels in the vitreous cavity after intravenous administration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4930.
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Purpose: To investigate the protein binding of fosfomycin in human vitreous in–vitro (part 1), and to investigate the penetration of intravenously administered fosfomycin into the human vitreous in a non–randomized prospective trial.(part 2) Methods: Part 1: After harvesting vitreous from donor eyes, six vitreous samples for three different drug concentrations of fosfomycin were spiked. Following an ultrafiltration procedure, the unbound vitreous concentrations of fosfomycin was determined using a standardized gas chromatographic spectrographic method. Part 2: Thirty patients undergoing vitrectomy received an intravenous dose of 200mg/ kg body weight fosfomycin before surgery. Specimens of vitreous and blood were obtained during surgery 0.5, 1, 2, 4, 6, 12 hours after the end of the intravenous infusion, and analyzed using a standardized gas chromatographic spectrographic method. Results: Part 1: With respect to the different drug concentrations, the protein–unbound fraction of fosfomycin ranged between 90–100%. Part 2: Vitreous concentrations from 52.37 to 140.58 µg/ml were reached between 20 and 855 minutes after drug administration. Serum concentrations from 65.64 to 987.65 µg/ml were reached between 20 and 855 minutes after drug administration. The mean peak concentration in vitreous was 120 mg/ml, reached 2 hours after administration. The mean fosfomycin concentration in vitreous exceeded 80 mg/ml throughout the observation period of 30 minutes to 14 hours after administration. The mean serum peak level was about 1mg/ml, reached 30 minutes after administration. The mean serum drug concentration was 100 µg/ml 14 hours after administration. Conclusion: The high percentage of unbound fosfomycin might be of advantage in the therapy of intravitreal infections. Fosfomycin concentrations in vitreous exceeded the in vitro measured minimum inhibitory concentration of fosfomycin for 90% (MIC90) of all clinically relevant gram–positive germs (incl. MRSA strains) in bacterial endophthalmitis. Thus, fosfomycin exhibits a pharmacokinetic profile, which appears to offer an alternative to other broad–spectrum antibiotics. Its usefulness in perioperative prophylaxis, as initial therapy after penetrating or perforating injury, or, possibly, in the treatment of therapy–resistant endophthalmitis has to be evaluated. None.
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