An antimicrobial peptide can enhance the activity of a fluoroquinolone in reducing the colony counts of fluoroquinolone‐resistant MRSA in the NZW rabbit keratitis model

Abstract

AbstractPurpose Future therapy of ocular infections may depend on enhancing current drugs if no new drugs are developed. We tested whether an antimicrobial peptide, Nisin (NIS) could enhance the activity of ciprofloxacin (CIP) in a NZW rabbit keratitis model.Methods A total of 48 rabbits were inoculated intrastromally in both eyes with ~1000 CFU of fluoroquinolone and methicillin‐resistant Staphylococcus aureus. After 4 h, the rabbits were divided equally into 4 treatment groups: 1) 0.075% NIS; 2) 0.3% CIP; 3) 0.075% NIS + 0.3% CIP; 4) PBS. Topical treatment was instilled in both eyes every 15 min for 5 hours. One hour after treatment the corneas were harvested, homogenized, and processed for colony counts. Colony counts were Log10 transformed and analyzed using ANOVA. The data is expressed as mean ± sd Log10 CFU/ml.Results CIP alone (6.76 ± 0.35) demonstrated no difference in colony counts compared to PBS (6.87 ± 0.30) (p>0.05). NIS alone (4.90 ± 1.84) significantly decreased colony counts compared to PBS and CIP (p<0.05). NIS + CIP (3.84 ± 2.01) significantly decreased colony counts compared to NIS alone, CIP alone, and PBS (p<0.05).Conclusion Combination therapy with 0.075% NIS and 0.3% CIP significantly decreased colony counts compared to PBS and either drug alone. This study provides “proof of principle” that in vivo enhancement of antibiotics can be achieved and may be evaluated using a rabbit model. Commercial interest