Immunity to lysostaphin and its therapeutic value for ocular MRSA infections in the rabbit.
OBJECTIVE
To determine the effects of immunization against lysostaphin on the bactericidal action of lysostaphin in ocular tissue and the possible induction of allergic reactions.


METHODS
Rabbits were immunized against lysostaphin by subcutaneous, intranasal, or topical routes. Anti-lysostaphin antibody titers were determined by ELISA and by neutralization of lysostaphin. Methicillin-resistant Staphylococcus aureus was intrastromally or intravitreously injected into rabbit eyes. Eyes were treated either topically with drops of lysostaphin (0.3%) or with a single intravitreous injection (0.1 mL) of lysostaphin (0.1%). At the time of death, corneas or vitreous humors were cultured to determine the number of colony forming units (CFU).


RESULTS
Rabbits in keratitis experiments that were immunized subcutaneously, intranasally, or topically had serum antibody titers of 10,240, 187, and 1,867, respectively, and neutralization titers of 8 or less. In both normal and immunized rabbits with keratitis, lysostaphin significantly reduced the log CFU to less than 1 log, whereas the untreated eyes contained more than 10(6) CFU/cornea (P < or = 0.0001). Rabbits that were subcutaneously or topically immunized for endophthalmitis experiments had serum antibody titers of 1636 or 137, respectively, and neutralization titers of 2 or less. A single intravitreous injection of lysostaphin (0.1%) sterilized all eyes of immunized and nonimmune rabbits with endophthalmitis. No adverse effects were observed with the administration of lysostaphin to either normal or immunized rabbit eyes.


CONCLUSIONS
Lysostaphin treatment of immunized rabbits was effective in treating S. aureus-infected eyes, despite the presence of anti-lysostaphin antibody. No adverse reactions were produced by administration of lysostaphin to immunized rabbits.
Dajcs
Joseph J
JJ
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center in New Orleans, New Orleans 70112, USA.
Thibodeaux
Brett A
BA
Girgis
Dalia O
DO
Shaffer
Megan D
MD
Delvisco
Stephen M
SM
O'Callaghan
Richard J
RJ
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000276:immunology / Q000627:therapeutic use*; D000917:Antibody Formation / Q000276:immunology; D015169:Colony Count, Microbial; D003319:Corneal Stroma / Q000382:microbiology; D009877:Endophthalmitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D015818:Eye Infections, Bacterial / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D007109:Immunity; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D007634:Keratitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D008248:Lysostaphin / Q000276:immunology / Q000627:therapeutic use*; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D011817:Rabbits; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification*; D014822:Vitreous Body / Q000382:microbiology
D000891:Anti-Infective Agents, Local; D007074:Immunoglobulin G; D008248:Lysostaphin; D008712:Methicillin