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J. W. Proksch, A. Chappa, W. Haas, T. W. Morris; Besifloxacin, Moxifloxacin, and Gatifloxacin Ocular Tissue AUC/MIC Ratios for Fluoroquinolone-Resistant Organisms. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2673.
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The pharmacokinetic/pharmacodynamic (PK/PD) relationship between fluoroquinolone drug levels and in vitro antibacterial activity is widely accepted as a useful surrogate for predicting bacterial eradication. The purpose of this investigation was to evaluate the ocular PK/PD relationship for besifloxacin, moxifloxacin, and gatifloxacin using ocular tissue PK data, along with in vitro MIC90 values for these agents against methicillin- and ciprofloxacin-resistant S. aureus (MRSA-CR) and S. epidermidis (MRSE-CR).
Ocular tissue levels for each agent in rabbits were measured after topical instillation of besifloxacin ophthalmic suspension (0.6%), moxifloxacin (0.5% solution), or gatifloxacin (0.3% solution). The 24-hr area under the concentration-time curve (AUC24) for total drug (bound and free) was determined for all compounds in tears, conjunctiva, cornea, and aqueous humor. Minimum inhibitory concentrations (MICs) were determined according to CLSI procedures for 20 MRSA-CR isolates and 81 MRSE-CR isolates.
MIC90 values for besifloxacin, moxifloxacin, and gatifloxacin were 4, 32, and 64 µg/mL, respectively, against MRSA-CR, and 4, 64, and 128 µg/mL, respectively, against MRSE-CR. Besifloxacin achieved an AUC24/MIC90 ratio of 763 in tears, compared with values ≤10 for moxifloxacin and gatifloxacin. In other tissues, the AUC24/MIC90 values were <10 for all compounds. However, in conjunctiva, besifloxacin AUC24/MIC90 values were 6-11-fold higher than moxifloxacin and 19-38-fold higher than gatifloxacin. In cornea, besifloxacin AUC24/MIC90 values were 3-6-fold higher than moxifloxacin and 5-10-fold higher than gatifloxacin. In aqueous humor, besifloxacin AUC24/MIC90 values were 1.5-3-fold higher than moxifloxacin and 5-9-fold higher than gatifloxacin.
Taken together, the ocular tissue distribution and in vitro activity of besifloxacin against ciprofloxacin-resistant strains of MRSA and MRSEresult in a highly favorable PK/PD profile for besifloxacin against these fluoroquinolone-resistant organisms.
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