A Randomized Trial Assessing the Clinical Efficacy and Microbial Eradication of 1% Azithromycin Ophthalmic Solution vs Tobramycin in Adult and Pediatric Subjects with Bacterial Conjunctivitis

Abstract

Objective: The study was designed to evaluate the efficacy of an ophthalmic formulation of 1% azithromycin in DuraSite® (AzaSite™, InSite Vision, Alameda CA, USA) and demonstrate equivalence with 0.3% tobramycin ophthalmic solution, USP, for the treatment of bacterial conjunctivitis as defined by the resolution of clinical signs and the eradication of pathogens. Design: Prospective, randomized, active-controlled, double-masked, phase 3 trial conducted at 47 US sites between 6 August 2004 and 6 October 2005. Participants: Subjects aged 1 year or older with diagnosis of acute bacterial conjunctivitis. Methods: Bacteriologically confirmed participants received either 1% azithromycin in Dura-Site (n = 159) or tobramycin (n = 157). Masked study medications were dosed 4 times a day for 5 days. Participants in the 1% azithromycin in DuraSite group were dosed twice a day with active drug on days 1 and 2 and once daily on days 3 through 5. The other doses were vehicle. Clinical signs and bacterial cultures were evaluated at visit 3 (day 6 + 1). Results: Clinical resolution was observed in 79.9% of participants in the 1% azithromycin in DuraSite group, as compared with 78.3% of those in the tobramycin group (95% CI: −7.4–10.5). Bacterial eradication was 88.1% in the 1% azithromycin in DuraSite group vs 94.3% in the tobramycin group (95% CI: −12.4–0.0). Analyses of resistance confirmed that 1% azithromycin in DuraSite eradicated Staphylococci and Streptococci strains that are commonly resistant to azithromycin, erythromycin, and fluoroquinolones. Conclusions: The efficacy of 1% azithromycin in DuraSite and tobramycin are equivalent; however, this formulation of azithromycin also permits effective dosing intervals of twice a day on days 1 and 2 followed by once daily on the last 3 days of therapy, for a total of 65% fewer doses. In vitro, the killing spectrum of 1% azithromycin in DuraSite appears to be enhanced relative to 1% azithromycin without DuraSite.