The Prophylactic Effectiveness of Two Fluoroquinolones on Staphylococcus aureus in Rabbit Eyes

1. The Prophylactic Effectiveness of Two Fluoroquinolones on Staphylococcus aureus in Rabbit Eyes Balzli C, Caballero A, Tang A, Weeks A, O’Callaghan R University of Mississippi Medical Center, Microbiology Department, Jackson, MS The authors of this poster have received research funding and travel expenses from Alcon Laboratories Inc.

2. Introduction • Staphylococcus aureus represents a significant infectious agent causing keratitis and endophthalmitis associated with penetrating surgery (i.e. cataract surgery). • S. aureus, particularly methicillin-resistant S. aureus (MRSA), infections can be very damaging to the eye and is increasingly difficult to treat. • Topical fluoroquinolones are commonly used prophylactically and as treatment for such infections due to their spectrum of coverage and overall activity, as well as their ability to penetrate tissues.

3. Introduction • The effectiveness of fluoroquinolones has been demonstrated many times in experimental MRSA keratitis models. • In the past, gauging the bactericidal effectiveness of these drugs on S. aureus in the anterior chamber has relied on in vitro data such as drug concentrations in the aqueous humor and minimum inhibitory concentrations (MIC) because S. aureus typically dies within the rabbit anterior chamber. • In these studies, a clinical isolate of MRSA was found to grow in the anterior chamber and was used to quantify the prophylactic bactericidal effectiveness of moxifloxacin and besifloxacin, a new fluoroquinolone, in the rabbit cornea and anterior chamber.

4. Growth of MRSA659 in the Anterior Chamber USA300 – Community Acquired MRSA(Strain NRS659*) 7 6 5 LogCFU/ml 4 3 2 1 0.5 2 4 6 8 10 Hours Post-Infection 10hr PI 106 CFU inoculum : n ≥ 3 / time point * Network on Antimicrobial Resistance in S. aureus

5. moxifloxacin 0.06 µg/ml n = 6 besifloxacin 0.03 µg/ml MRSA659 Susceptibility to Fluoroquinolones • MICs of the commercial ophthalmic formulations of moxifloxacin (0.5%) and besifloxacin (0.6%) were determined. • After determining the growth and susceptibility of MRSA659, the prophylactic effectiveness of the two fluoroquinolones were tested in keratitis and endophthalmitis infection models in the rabbit eye.

6. Prophylactic Treatment Topical application of drug (45 µl) Infect cornea or anterior chamber Treatment Groups: 0.6% besifloxacin (Besivance) 45 µl 0.5% moxifloxacin (Vigamox) 45 µl Untreated 30 min 30 min Rinse eye with PBS Quantify CFU of anterior chamber

7. 30 Minute Prophylaxis of MRSA Keratitis Inoculation = 106 CFU : n = 4/group 6 5 * Log CFU/Cornea 4 5.72 ± 0.21 4.01 ± 0.22 5.98 ± 0.05 3 2 Moxifloxacin Besifloxacin Untreated * - Fewer CFU/cornea than besifloxacin treated or untreated corneas (P ≤ 0.0023)

8. 30 Minute Prophylaxis of MRSA Endophthalmitis Inoculation = 106 CFU : n = 8/group 6 5 * 4 Log CFU/ml Aqueous 3 4.80 ± 0.17 3.30 ± 0.12 5.01 ± 0.14 2 1 Moxifloxacin Besifloxacin Untreated * - Fewer CFU/cornea than besifloxacin treated or untreated corneas (P ≤ 0.0001)

9. Conclusions • Moxifloxacin was highly effective prophylactically for MRSA within the cornea or anterior chamber. • Besifloxacin demonstrated insignificant prophylactic effectiveness in the cornea or the aqueous humor compared to untreated eyes.