Comparison of besifloxacin, gatifloxacin, and moxifloxacin against strains of pseudomonas aeruginosa with different quinolone susceptibility patterns in a rabbit model of keratitis.
OBJECTIVE
Determine the effectiveness of topical besifloxacin, gatifloxacin, and moxifloxacin in treating keratitis caused by 2 strains of Pseudomonas aeruginosa with different quinolone susceptibility profiles.


METHODS
Minimal inhibitory concentrations (MICs) were determined for each fluoroquinolone. Sequence analysis was performed on the quinolone resistance determining regions of the ciprofloxacin/levofloxacin-resistant strain. Rabbit corneas were injected with 10 colony-forming units (CFU). After 16 hours, phosphate-buffered saline, besifloxacin (6 mg/mL), gatifloxacin (3 mg/mL), or moxifloxacin (5 mg/mL) was applied topically every 15 minutes for 5 doses, then every 30 minutes for 14 doses. Eyes were examined pre- and posttreatment. Corneas were harvested for bacterial quantitation.


RESULTS
MICs against the fully susceptible strain were 0.5, 0.25, and 0.5 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. The MICs against the ciprofloxacin/levofloxacin-resistant strain were 2, 16, and 32 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. Sequence analysis revealed amino acid mutations in all 4 fluoroquinolone target genes. None of the treatments had an effect on clinical severity of eyes infected with the fully susceptible strain (P > 0.05); however, all were effective at significantly reducing the bacterial CFU in the corneas (P < 0.05). For the ciprofloxacin/levofloxacin-resistant strain, clinical scores of besifloxacin-treated eyes were significantly lower than moxifloxacin-treated eyes (P < 0.037). The quantities of ciprofloxacin/levofloxacin-resistant bacteria recovered from corneas of all treatment groups were significantly lower than those recovered from phosphate-buffered saline-treated corneas (P < 0.05). Besifloxacin-treated eyes had significantly lower CFU recovered as compared with that of gatifloxacin- and moxifloxacin-treated eyes (P < 0.05).


CONCLUSIONS
These results support clinical investigation of the effectiveness of besifloxacin in treating Pseudomonas keratitis.
Sanders
Melissa E
ME
Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Moore
Quincy C
QC
Norcross
Erin W
EW
Sanfilippo
Christine M
CM
Hesje
Christine K
CK
Shafiee
Afshin
A
Marquart
Mary E
ME
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D001381:Azepines / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D024881:Drug Resistance, Bacterial; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D000077734:Gatifloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D016133:Polymerase Chain Reaction; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D011804:Quinolines / Q000627:therapeutic use; D011817:Rabbits; D017422:Sequence Analysis, DNA
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001381:Azepines; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D011804:Quinolines; C522124:besifloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin