Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis

Purpose. The purpose of this study was to determine the effectiveness of mupirocin and polymyxin B, alone and in combination, in vitro and in vivo using rabbit models of Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis. Methods. Rabbit eyes were intrastromally injected with 1,000 colony-forming units (CFUs) of P. aeruginosa or S. marcescens or 100 CFUs of S. aureus. Rabbits were then treated with 2.7 mg/mL mupirocin, 10,000 U/mL polymyxin B, a mupirocin:polymyxin B combination, or 0.3% ciprofloxacin. Vehicle and untreated controls were also included. Treatment schedules depended on the strain injected. The number of CFUs was determined for all eyes after treatment. Results. The mupirocin:polymyxin B combination was effective for all three genera both in vitro and in vivo. For S. aureus keratitis, the mupirocin:polymyxin B combination was more effective than either drug alone and significantly reduced the log number of bacteria in the cornea by more than 3 logs compared with the vehicle or untreated controls (p less than or equal to 0.0016). For P. aeruginosa, the mupirocin:polymyxin B combination treatment significantly reduced the number of CFUs per cornea relative to the individual drugs, vehicle, or untreated controls (p less than or equal to 0.016). For S. marcescens, the mupirocin:polymyxin B combination therapy significantly reduced the number of bacteria in rabbit corneas relative to the individual drugs, vehicle, or untreated groups (p less than or equal to 0.0001). Therapy with the mupirocin:polymyxin B combination was equivalent to ciprofloxacin therapy (p = 0.80). Conclusion. The mupirocin:polymyxin B combination was effective in treating experimental S. aureus, P. aeruginosa, and S. marcescens keratitis.