Besifloxacin (Optura, Bausch & Lomb) was found to be more effective than gatifloxacin and moxifloxacin in reducing the number of methicillin-resistant Staphylococcus aureus organisms in the cornea when applied topically 10 to 18 hours after infection.
Editor's Note: Besifloxacin (Besivance) received FDA approval May 29. Thefollowing article was printed prior to the approval of the drug, when itsproposed proprietary name was Optura.
The impetus for the study centered on concerns over the increasing problem of antibiotic resistance, said Dr. Marquart, assistant professor, Department of Microbiology, University of Mississippi Medical Center, Jackson. Limiting an antibiotic only to ocular use might limit the increasing systemic bacterial resistance to besifloxacin as has occurred with other fluoroquinolones, she added.
"We thought that this time frame might be clinically relevant because patients do not necessarily present immediately for treatment," she said.
The results of this study indicated that besifloxacin was more efficacious in reducing the bacteria in the cornea compared with moxifloxacin, gatifloxacin, and a control group. None of the treatments, however, resulted in eyes that looked better than the controls regarding the clinical signs (corneal edema, iritis, corneal infiltration with neutrophils, and conjunctival swelling and redness), and the clinical scores among the treatment groups were similar. This study is scheduled for publication in Cornea this year.
Earlier treatment more effective?
The results of that study led Dr. Marquart and colleagues, in turn, to the hypothesis that earlier treatment may be more effective for reducing the clinical signs of MRSA keratitis, which is what they addressed in the study under discussion, in which they evaluated treatment at 10 to 18 hours after infection.
The investigators injected 100 colony-forming units (CFU) of MRSA (blood isolate, G.V. Sonny Montgomery VA Medical Center, Jackson, MS) intrastromally into rabbit corneas. Ten hours after infection, 1 drop of phosphate-buffered saline (control), besifloxacin, gatifloxacin, or moxifloxacin was applied to each eye every 15 minutes for five doses and then every 30 minutes for 14 doses. The eyes were examined by slit-lamp biomicroscopy before and after treatment. The corneas were harvested from all rabbit groups to quantify the bacteria.
Minimal inhibitory concentrations were determined in vitro for each fluoroquinolone, Dr. Marquart said.
"Besifloxacin was the most effective of the three drugs in reducing the bacterial CFU after treatment compared with the control group (p < 0.001)," she said. The baseline average log10 CFU of MRSA recovered from besifloxacin-treated corneas was 3.569 ± 0.378, which was significantly lower than the CFU recovered from the gatifloxacin-treated corneas (5.652 ± 0.396) and the moxifloxacin-treated corneas (6.243 ± 0.387) (p < 0.001).
All of the fluoroquinolones tested in this study reduced the clinical severity of the clinical signs as a result of earlier treatment.
This earlier treatment regimen is important for patients. Dr. Marquart demonstrated a rabbit with corneal erosion that was already present 9 hours after infection with MRSA, which underscores how rapidly this bacterium spreads.
"There is a need for development of new antibiotic and antimicrobial therapies to treat ocular infection," she concluded. "We found that besifloxacin is more capable of reducing bacteria in MRSA keratitis and that besifloxacin is a viable treatment regimen that is less susceptible to MRSA keratitis."