Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit

PURPOSE. To determine the efficacy of lysostaphin treatment of methicillin- sensitive and methicillin-resistant Staphylococcus aureus (MRSA) keratitis in a rabbit model. METHODS. The sensitivity to lysostaphin and vancomycin were compared for 34 MRSA and 12 methicillin-sensitive strains. Methicillin-resistant S. aureus strain 301 (MRSA 301) or a methicillin-sensitive strain of low virulence, ISP546, was intrastromally injected into rabbit corneas. Rabbit eyes were t reated topically every 30 minutes from 4 to 9 or 10 to 15 hours postinfecti on with 0.28% lysostaphin or 5.0% vancomycin. Rabbits were killed and corne as were excised and cultured to determine the number of colony forming unit s (CFU) per cornea. RESULTS. Ninety percent minimal inhibitory concentrations were at least 19- fold lower for lysostaphin than for vancomycin. With early therapy (4-9 hou rs postinfection) lysostaphin sterilized all MRSA 301-infected corneas, whe reas untreated corneas contained 6.52 log CFU/cornea (P less than or equal to 0.0001). Corneas infected with MRSA 301 and treated similarly with vanco mycin retained 2.3 +/- 0.85 log CFU/cornea, and none were sterile. When the rapy was begun later (10-15 hours postinfection) the residual bacteria in l ysostaphin-treated eyes were significantly less numerous than in vancomycin -treated eyes (0.58 +/- 0.34 vs. 5.83 +/- 0.16 log CFU/cornea, respectively ; P less than or equal to 0.0001). Three experiments were performed to demo nstrate that lysostaphin penetrated the cornea to kill bacteria in vivo; ly sostaphin-treated eyes were found to recover from infection, bacteria that did not cause epithelial defects (ISP546) were susceptible to lysostaphin, and inhibition of lysostaphin when harvesting corneas did not alter the obs erved therapeutic values of lysostaphin. CONCLUSIONS. Lysostaphin is very effective in treating keratitis mediated b y methicillin-sensitive or methicillin-resistant S. aureus.