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Q. C. Moore, III, M. E. Sanders, E. W. Norcross, A. Shafiee, M. E. Marquart; Efficacy of Besifloxacin in the Treatment of Quinolone-Resistant Pseudomonas aeruginosa Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3103.
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To determine the effectiveness of topically applied besifloxacin (0.6%), gatifloxacin (0.3%), and moxifloxacin (0.5%) for the treatment of experimental quinolone-resistant Pseudomonas aeruginosa (QRPA) keratitis.
One thousand colony-forming units (CFU) of QRPA (urine isolate, G.V. Sonny Montgomery V.A. Medical Center, Jackson, MS) were injected intrastromally into rabbit corneas. Sixteen hours after infection, one topical drop of PBS, besifloxacin, gatifloxacin, or moxifloxacin was applied to each eye every 15 minutes for 5 doses and then every 30 minutes for 14 doses. Eyes were examined before and after treatment by slit lamp biomicroscopy. Corneas were harvested from treated and untreated rabbits for the quantitation of bacteria. Minimal inhibitory concentrations (MICs) were determined in vitro for each fluoroquinolone.
The baseline log10 CFU recovered from corneas prior to treatment was 6.104 ± 0.932. The average log10 CFU of QRPA recovered from besifloxacin-treated corneas (3.875 ± 0.487) was not statistically different from the corneas treated with gatifloxacin (5.415 ± 0.306) or moxifloxacin (5.455 ± 0.503; P > 0.050; n = 12 corneas per group). All three fluoroquinolones were effective in reducing bacterial CFU in infected corneas compared to PBS (P < 0.050). The average log10 CFU recovered from the PBS-treated corneas at 25 hours post-infection was 7.706 ± 0.299 (n = 10). The average clinical scores of besifloxacin-treated eyes (6.109 ± 0.321; n = 16) and gatifloxacin-treated eyes (7.648 ± 0.660; n = 16) were not significantly different from the average clinical score of PBS-treated eyes (7.071 ± 0.356; n = 14; P > 0.050). However, the besifloxacin-treated eyes had a significantly lower average clinical score compared to eyes treated with gatifloxacin (7.648 ± 0.660; n = 16; P = 0.045) or moxifloxacin (9.047 ± 0.570; n = 16; P < 0.001). Eyes treated with moxifloxacin had a significantly higher average score compared to control eyes (P = 0.008). The MICs for besifloxacin, gatifloxacin and moxifloxacin against the QRPA strain were 2, 16, and 32 µg/ml, respectively.
These data show that besifloxacin is as effective as gatifloxacin and moxifloxacin in reducing the CFU of QRPA in the cornea following topical treatment at 16 to 24 hours post-infection. Besifloxacin treatment causes significantly reduced clinical severity compared to gatifloxacin or moxifloxacin treatment. Moxifloxacin treatment increases the clinical severity compared to control treatment with PBS. Moreover, besifloxacin has the lowest MIC against the QRPA strain.
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