Frequent Dosing With Topical 1% Azithromycin is Effective in Reducing Azithromycin-Resistant Pseudomonas aeruginosa Colony Counts in a NZW Rabbit Model

Abstract

Purpose:: Azithromycin (AZ) is a macrolide antibiotic used systemically for the treatment of otitis media, sinusitis, and community acquired pneumonia. 1% topical AZ formulated in DuraSite has just completed Phase III clinical trials for the treatment of bacterial conjunctivitis. Results from these studies indicated successful treatment of conjunctivitis caused by Pseudomonas aeruginosa (PA), a bacterial species which is usually resistant to AZ. The goal of the current study was to investigate whether treatment with topical 1% AZ could effectively reduce PA colony counts in a NZW rabbit keratitis model.

Methods:: A total of 24 NZW rabbits, in 2 separate trials, were inoculated intrastromally in both eyes with approximately 1000 CFU of an AZ-resistant (MIC = 24 µg/ml) PA ocular isolate. The rabbits were randomly divided into 4 treatment groups of 3 rabbits each per trial. At 16 hours post-inoculation, topical treatment was initiated in both eyes. Group I was treated with 1% AZ (AzaSite, InSite Vision, Alameda, CA) every half hour for 8 hours (AZ-q0.5). Group II was treated with 1% AZ every hour for 8 hours (AZ-q1). Group III was treated with 1% AZ every 2 hours for 8 hours (AZ-q2). Group IV was treated with saline (Control) every half hour for 8 hours (Con). One hour after therapy, the rabbits were euthanized and the corneas were homogenized to determine viable bacterial counts. The colony counts from both eyes were averaged, then were Log₁₀ converted and analyzed using ANOVA.

Results:: Trial 1 AZ-q0.5 (2.2 ± 2.0 [Mean ± standard deviation Log₁₀ CFU/ml]) demonstrated significantly fewer PA corneal colony counts compared with AZ-q1 (4.7 ± 0.4), AZ-q2 (5.1 ± 0.5), and Con (5.3 ± 0.5) (P=0.024). There were no differences among AZ-q1, AZ-q2, and Con. In Trial 2, both AZ-q0.5 (4.1 ± 0.2) and AZ-q1 (4.3 ± 1.6) demonstrated significantly fewer corneal PA colony counts compared with AZ-q2 (6.5 ± 0.2) and Con (6.7 ± 0.3) (p=0.008). There were no differences between AZ-q0.5 and AZ-q1 and between AZ-q2 and Con.

Conclusions:: Frequent dosing with topical AzaSite (1% AZ) was effective in reducing the number of AZ-resistant Pseudomonas aeruginosa colony counts in a NZW rabbit keratitis model. These results warrant subsequent studies to determine the role of azithromycin for the treatment of Pseudomonas aeruginosa keratitis.

Keywords: antibiotics/antifungals/antiparasitics • Pseudomonas • keratitis