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J. M. Joseph, R. G. Fiscella, K. A. Rodvold, M. Blair, L. Ulanski, J. Stokes, M. J. Shapiro, N. P. Blair; Aqueous and Vitreous Penetration of Linezolid and Levofloxacin After Oral Administration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):958. doi: https://doi.org/.
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The purpose of this study was to measure and evaluate the time course of drug concentrations achieved in plasma, aqueous (AQ), and vitreous (V) compartments after oral administration of linezolid and levofloxacin, prior to elective vitrectomy surgery.
Patients undergoing primary vitrectomy between April 2006 and April 2007 at UIC were randomly assigned to 1 of 5 groups. All subjects received a single oral dose of linezolid 600mg and levofloxacin 750mg between 1 hour and greater than 12 hours before the procedure: group A=1-3 hours; group B=3-6 hours; group C=6-9 hours; group D=9-12 hours; group E= > 12 hours. Antibiotic concentrations were determined by HPLC assay.
Mean plasma concentrations of linezolid and levofloxacin were similar to those previously reported. Concentrations achieved in AQ and V compartments are listed in Table 1.
This is the first study to investigate the time course to achievable therapeutic concentrations into the AQ and V compartments after concurrent administration of oral linezolid and levofloxacin. In addition, levofloxacin 750mg has not been studied prior to this study. Single doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentrations for 90% (MIC90) of common ocular gram positive and gram negative pathogens, including vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, streptococci, Escherichia coli, and Proteus mirabilis. Concentrations achieved in the AQ and V compartments exceeded that of the MIC90 of common ocular pathogens within 1-2 hours after drug administration. Generally, peak antibiotic concentrations were attained after 4 hours. Therapeutic concentrations were maintained for over 12 hours after drug administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of bacterial endophthalmitis.
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