Bacterial keratitis is common in horses. Left untreated or treated inadequately, the condition often leads to vision loss.1 Intensive antimicrobial treatment, topical atropine administration, systemic NSAID administration, and often surgery are necessary to maintain vision.1 For treatment to be successful, an antimicrobial with activity against the inciting pathogen must reach and maintain inhibitory concentrations within the cornea.
Initial treatment of bacterial keratitis is largely empirical because of the delay associated with obtaining the results of bacterial culture and antimicrobial susceptibility testing. Therefore, initial treatment is based on results of cytologic evaluation, and antimicrobials with a known spectrum of activity against the most common corneal bacterial pathogens are used. The bacteria most commonly isolated from horses with bacterial keratitis are Streptococcus equi subsp zooepidemicus, Pseudomonas aeruginosa, and Staphylococcus spp.2–4 Fluoroqui-nolones have a broad spectrum of activity against both gram-positive and gram-negative bacteria, with 97% of bacterial isolates from horses with bacterial ulcerative keratitis susceptible to ciprofloxacin.3 Although an increase in resistance of bacterial isolates from horses with bacterial ulcerative keratitis to fluoroquinolones has not yet been reported,4 increasing resistance to fluoroquinolones in human corneal pathogens5,6 has been documented, and such resistance may become apparent in equine corneal pathogens as the use of fluoroquinolones in horses increases.
To address the potential development of bacterial resistance to second-generation fluoroquinolones such as ciprofloxacin, third- and fourth-generation fluoroquinolones have been developed. These newer antimicrobials require that bacteria acquire 2 separate genetic mutations for resistance to develop instead of 1 as for the second-generation fluoroquinolones.7 Among the fourth-generation fluoroquinolones, moxifloxacin reportedly has greater corneal penetration8 and equal, or slightly lower, in vitro efficacy against common pathogens associated with keratitis in humans.9–11
Human pharmacokinetic studies12–15 have revealed that topical administration of ciprofloxacin by use of various dosing regimens consistently results in mean corneal drug concentrations that are higher than the MIC90 for the most common bacterial pathogens. In rabbits and humans, moxifloxacin has corneal and aqueous humor penetration superior to that of ciprofloxacin and other fluoroquinolones.8 None of the aforementioned studies involved evaluation of the corneal concentration of the drugs longer than 1 hour after the last administration. Although pharmacokinetic studies in equids are lacking, it has recently been shown that 1 topical application of 0.3% ciprofloxacin results in tear drug concentrations higher than the MIC90s for most pathogenic bacteria for as long as 6 hours after administration.16 This finding is similar to results in humans and rabbits.17–21 Knowing the extent of corneal penetration and the dosing regimens necessary to achieve therapeutic concentrations in equine ocular tissues would assist clinical management of infectious keratitis. The purpose of the study reported here was to determine concentrations of ciprofloxacin and moxifloxacin in tears, corneal stroma, and aqueous humor after topical administration via 3 clinically relevant dosing regimens in ophthalmologically normal horses.
High-performance liquid chromatography
Minimal inhibitory concentration
Minimal inhibitory concentration that will inhibit 90% of bacterial growth
Falcon Pharmaceuticals Ltd, Fort Worth, Tex.
Alcon Laboratories Inc, Fort Worth, Tex.
Haag-Streit UK Ltd, Harlow, Essex, England.
Miltex Inc, York, Pa.
2695 Separations Module, Waters, Milford, Mass.
Atlantis dc18 column, Waters, Milford, Mass.
Atlantis guard column, Waters, Milford, Mass.
2475 Fluorescence Detector, Waters, Milford, Mass.
Empower2, Waters, Milford, Mass.
SigmaPlot, version 11.0, Systat Software Inc, San Jose, Calif.
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