Cornea · 2011
Comparison of besifloxacin, gatifloxacin, and moxifloxacin against strains of pseudomonas aeruginosa with different quinolone susceptibility patterns in a rabbit model of keratitis.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sanders Melissa E, Moore Quincy C, Norcross Erin W, Sanfilippo Christine M, Hesje Christine K, Shafiee Afshin, Marquart Mary E
Аннотация
PURPOSE: 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.
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.
Предметные рубрики MeSH
Administration, TopicalAnimalsAnti-Bacterial AgentsAza CompoundsAzepinesColony Count, MicrobialCorneal UlcerDNA, BacterialDisease Models, AnimalDisease SusceptibilityDrug Resistance, BacterialEye Infections, BacterialFemaleFluoroquinolonesGatifloxacinMaleMicrobial Sensitivity TestsMoxifloxacinPolymerase Chain ReactionPseudomonas InfectionsPseudomonas aeruginosaQuinolinesRabbitsSequence Analysis, DNA