To investigate the therapeutic role of trovafloxacin mesylate, a newer-generationfluoroquinolone with an expanded spectrum of activity, in the treatment ofexperimental bacterial keratitis.
Susceptibility studies were performed on various strains of ocular isolatesto determine the minimum inhibitory concentration (MIC) of trovafloxacin comparedwith ciprofloxacin and ofloxacin, using the E-test method. Pharmacokineticstudies were performed by a single topical administration of trovafloxacinto rabbit eyes with either an intact or denuded corneal epithelium. Aqueoushumor, vitreous, and corneal concentrations of trovafloxacin were determinedat different time points. Experimental bacterial keratitis studies were performedin rabbit eyes. Three identical studies were conducted using Staphylococcus aureus, Streptococcus pneumoniae,or Pseudomonas aeruginosa. Therapy groups included0.5% trovafloxacin, 0.3% ciprofloxacin, 0.3% ofloxacin, and isotonic sodiumchloride solution. After 12 hours of drops administration, corneas were excised,homogenized, and serially plated. The main outcome measure was quantitativebacteriologic analysis for residual colony-forming units.
In vitro susceptibility study findings indicated that the MIC of trovafloxacinwas significantly lower than the MIC of ciprofloxacin and ofloxacin for S aureus, S pneumoniae, and Haemophilus influenzae, lower than the MIC of ciprofloxacinand ofloxacin for Staphylococcus epidermidis, andintermediate between ciprofloxacin and ofloxacin for P aeruginosa. Pharmacokinetic studies showed a significant concentration of trovafloxacinin the treated corneas, especially in eyes with a denuded epithelium. Allserum samples had undetectable trovafloxacin concentrations. Experimentalkeratitis studies showed a statistically significant decrease of colony-formingunits in trovafloxacin-treated eyes in the S aureus modeland a similar decrease in the S pneumoniae and P aeruginosa models.
Topical 0.5% trovafloxacin proved to be an effective ocular medicationfor the therapy of gram-positive and gram-negative keratitis.
Trovafloxacin may provide an excellent therapeutic alternative in bacterialkeratitis.