The effectiveness of lysostaphin therapy for experimental coagulase-negative Staphylococcus endophthalmitis.
OBJECTIVE
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 microg) 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 microg/ml for 90% of the 33 strains tested. Six methicillin-resistant strains of S. epidermidis (MRSE) had an average MIC of 0.74 micro g/ml. All other species had MIC values of =1.1 microg/ml, except for one strain of S. capitis (MIC = 15.6 microg/ml) and one S. haemolyticus (MIC = 1.41 microg/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.
Department of Microbiology, Immunology and Parasitology, LSU Health Sciences Center, New Orleans, Louisiana, USA.
Clare C
CC
McCormick
Joseph J
JJ
Dajcs
Julian M
JM
Reed
Mary E
ME
Marquart
Richard J
RJ
O'Callaghan
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D007267:Injections; D008248:Lysostaphin / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013210:Staphylococcus / Q000302:isolation & purification; D016896:Treatment Outcome; D014822:Vitreous Body / Q000382:microbiology
D000891:Anti-Infective Agents, Local; D008248:Lysostaphin