Comparison of Topical Chlorhexidine, Ciprofloxacin, and Fortified Tobramycin/Cefazolin in Rabbit Models of Staphylococcus and Pseudomonas Keratitis

Abstract

Abstract: : Purpose:Chlorhexidine was evaluated as a potential topical therapy for bacterial keratitis. Methods:Chlorhexidine(.1%) was compared to ciprofloxacin(.3%) and tobramycin(1.36%)/cefazolin(5%) in both in vitro and in vivo for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa infections. Minimum Inhibitory Concentration (MIC) was established for each organism with chlorhexidine, ciprofloxacin, cefazolin, and tobramycin using standardized methods. Animal experiments involved an intrastromal injection of 1000 colony forming units (CFU) of S. aureus or P. aeruginosa into rabbit corneas. A total of 96 corneas were infected and then treated with chlorhexidine, ciprofloxacin, or fortified tobramycin/cefazolin. The control was treated artificial tears. The rabbits were killed and the corneal buttons were removed. The corneal buttons were homogenized and diluted for quantitative culture. Colony counts in triplicate established the number of viable bacteria remaining after each antimicrobial therapy was completed. The total CFU was compared for the treated and control corneas. Results:The MIC data for S. aureus was in the susceptible range for all of the antimicrobial agents, while the data for P. aeruginosa showed resistance to only cefazolin. The MIC for chlorhexidine was <0.004% for both organisms. In the rabbit model of S. aureus keratitis, the median number of CFU for chlorhexidine(n=10), ciprofloxacin(n=10), tobramycin/cefazolin(n=12) and control(n=10) was 1.1x10₃, 4.7x10₄, 2.5x10₅, and 6.7x10₄ respectively. The only treatment that showed statistically significant reduction in CFU was chlorhexidine. In the rabbit model of P. aeruginosa keratitis, CFU were significantly reduced with all treatments compared to the control. The median number of CFU for chlorhexidine(n=12), ciprofloxacin(n=12), tobramycin/cefazolin(n=12), and control(n=12) was 2.0x10₅, 3.5x10₁, 3.0x10₄, and 5.5x10₆ respectively. Conclusion:Chlorhexidine is a potential therapy for bacterial keratitis, in particular S. aureus keratitis. Chlorhexidine demonstrated superior activity against both microorganisms in vitro. However, MIC data did not accurately predict in vivo success for all treatments. In the S. aureus keratitis model, chlorhexidine was the only treatment that significantly reduced CFU. In the P. aeruginosa keratitis model all the treatments reduced the number of CFU; however, ciprofloxacin was the most effective.

Keywords: 328 bacterial disease • 449 keratitis • 319 antibiotics/antifungals/antiparasitics