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Eric G. Romanowski, Kathleen A. Yates, Francis S. Mah, Y J. Gordon, Regis P. Kowalski; An Antimicrobial Peptide Can Enhance the Activity of a Fluoroquinolone in Reducing Colony Counts of Fluoroquinolone-Resistant MRSA in the NZW Rabbit Keratitis Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6257.
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© ARVO (1962-2015); The Authors (2016-present)
Fluoroquinolone-resistant, methicillin-resistant Staphylococcus aureus (FQR-MRSA) ocular infections are increasing in number. Unfortunately, there are no new antibiotics in development to treat these ocular infections. An approach to solve this problem is to enhance the activity of older antibiotics with additional agents to make a combination more effective against resistant pathogens than either alone. To determine whether the activity of a highly resistant antibiotic could be enhanced, we tested whether combination therapy with ciprofloxacin (CIP) and an antimicrobial peptide (Nisin [NIS], a 34 amino acid amphiphilic antimicrobial peptide used as a food preservative) will have enhanced activity compared to either alone in reducing FQR-MRSA colony counts in the NZW rabbit keratitis model.
A total of 48 rabbits were inoculated intrastromally in both eyes with ~1000 CFU of FQR-MRSA. After 4 h, the rabbits were divided into 4 treatment groups (n=12/group): I) 0.075% NIS; II) 0.3% CIP; III) 0.075% NIS + 0.3% CIP; IV) PBS. Topical treatment was instilled in both eyes every 15 min. for 5 hours. One hour after the final dose, the corneas were harvested, homogenized, and colony counts were performed. Colony count data were Log10 transformed and analyzed statistically using a one-way ANOVA with Fisher’s pairwise comparisons. The data is expressed as mean ± sd Log10 CFU/ml.
CIP treatment alone (6.76 ± 0.35 CFU/ml) demonstrated no difference in the number of colony counts compared to PBS (6.87 ± 0.30 CFU/ml) (p>0.05). NIS alone (4.90 ± 1.84 CFU/ml) significantly decreased the number of colony counts compared to PBS and CIP (p<0.05). NIS + CIP (3.84 ± 2.01 CFU/ml) significantly decreased the number of colony counts compared to NIS alone, CIP alone, and PBS (p<0.05).
Combination therapy with 0.075% NIS and 0.3% CIP demonstrated a significant decrease in FQR-MRSA colony counts compared to the PBS control and either drug alone. This study provides "proof of principle" that in vivo enhancement of topical antimicrobial agents can be achieved and may be evaluated using the NZW rabbit keratitis model.
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