The Effectiveness of Lysostaphin Therapy for Experimental Coagulase-Negative Staphylococcus Endophthalmitis

Abstract

Purpose: To quantitatively determine the effectiveness of lysostaphin therapy for experimental endophthalmitis mediated by coagulase-negative Staphylococcus species, the leading cause of postsurgical endophthalmitis. Methods: Minimal inhibitory concentrations (MIC) of lysostaphin were determined for 54 isolates representing the following species: S. epidermidis, S. warneri, S. haemolyticus, S. cohnii, S. simulans, and S. capitis. The effectiveness of lysostaphin therapy was tested in an experimental model of endophthalmitis by intravitreally injecting log phase bacteria (100 colony-forming units; cfu) into rabbit eyes (n ≥ 3 eyes per group). At 8 hr postinfection (PI), lysostaphin (250 μg) was injected intravitreally, and the number of cfu/ml of vitreous was determined at 24 hr PI. Results: Average MIC for S. epidermidis was 0.7 μ g/ml for 90% of the 33 strains tested. Six methicillin-resistant strains of S. epidermidis (MRSE) had an average MIC of 0.74 μ g/ml. All other species had MIC values of ≤1.1 μg/ml, except for one strain of S. capitis (MIC = 15.6 μ g/ml) and one S. haemolyticus (MIC = 1.41 μ g/ml). At 24 hr PI, all untreated eyes had between 5.7 and 8.08 log cfu/ml vitreous humor. Treatment with lysostaphin significantly reduced the cfu/ml as compared with untreated eyes for 13 strains tested in vivo (p ≤ 0.020), but not for two S. haemolyticus strains (p ≥ 0.13), two MRSE strains (p ≥ 0.544), or one S. cohnii strain (p = 0.1366). Treatment with lysostaphin reduced the cfu/ml of methicillin-sensitive S. epidermidis strains by 6 logs; for S. warneri, there was a 2 log reduction; and for the other species a 4 log reduction in cfu/ml relative to untreated eyes. Conclusions: Lysostaphin was mostly effective in treating coagulase-negative staphylococcal experimental endophthalmitis.

KEYWORDS:

• coagulase-negative
• endophthalmitis
• lysostaphin
• Staphylococcus