Preclinical study compares fluoroquinolones

August 1, 2007

The efficacy of gatifloxacin and moxifloxacin for preventing methicillin-resistant Staphylococcus aureus (MRSA) keratitis was investigated in a rabbit model. Animals were pretreated with one of the two fourth-generation fluoroquinolones or BSS, received a midstromal injection with an inoculum of MRSA, and then study treatment continued for up to 96 hours postinjection. Gatifloxacin-treated eyes demonstrated less inflammation and infection, and lower numbers of recovered MRSA than moxifloxacin-and BSS-treated animals.

Key Points

A study evaluating the fourth-generation fluoroquinolones for prophylactic treatment of methicillin-resistant Staphylococcus aureus (MRSA) keratitis in a rabbit model found treatment with gatifloxacin 0.3% ophthalmic solution (Zymar, Allergan) was associated with fewer signs of inflammation, infection, and bacterial recovery compared with both moxifloxacin 0.5% ophthalmic solution (Vigamox, Alcon) and balanced salt solution (BSS)-treated controls, reported investigators at the annual meeting of the Association for Research in Vision and Ophthalmology.

A total of 30 animals were divided into three groups, and each animal was treated with one drop of the assigned study agent every 15 minutes for four doses. Immediately after the last dose, an inoculum containing 103 colony forming units (cfu) of a clinical isolate of MRSA was injected into the midstroma. Treatment continued with another dose of study agent given immediately and then for up to another 96 hours at a frequency based on the labeled directions for the fluoroquinolones (Q6H for gatifloxacin, Q8H for moxifloxacin) and Q6H for the controls.

"MRSA keratitis is a sight-threatening complication of laser vision correction surgery. Unfortunately, previously available antibacterial agents administered for infection prophylaxis, including the third-generation fluoroquinolones and aminoglycosides, have poor activity against these bacteria," said Luis E. Fernández de Castro, MD, instructor of ophthalmology, Magill Research Center for Vision Correction, Storm Eye Institute, Medical University of South Carolina, Charleston.

Before he and colleagues conducted the prophylaxis study, they undertook a pilot study to determine the appropriate size of the MRSA inoculum for injection. Three different dilutions were tested, and 103 cfu was found to create reproducible clinical findings consistent with keratitis.

After MRSA was injected, the rabbits were examined clinically at the slit-lamp, and the severity of 11 signs of infection and inflammation was graded in masked fashion on a scale of 0 to 3. Five rabbits per group were killed at 48 hours postinjection, and the remaining five at 96 hours postinjection. Cornea and aqueous and vitreous humors were collected to determine the number of viable bacteria remaining.

The aqueous and vitreous remained culture-negative in all animals treated with gatifloxacin, whereas at 48 hours, a low level of bacteria (≤101 cfu) was detected in the aqueous of one animal each in the moxifloxacin and BSS groups and in the vitreous in two moxifloxacin-treated animals and one of the BSS controls. A single BSS-treated animal also was found to have bacteria in the vitreous (101 – 103 cfu) at 96 hours. None of the rabbits in the 0.3% gatifloxacin treatment group demonstrated bacterial growth from the aqueous or vitreous specimens.

"This indicates that topical prophylaxis with gatifloxacin or moxifloxacin can reach levels in the anterior chamber that can reduce bacterial growth, gatifloxacin doing so by 48 hours and moxifloxacin by 96 hours," noted Dr. Fernández de Castro.