Immunity to lysostaphin and its therapeutic value for ocular MRSA infections in the rabbit

Invest Ophthalmol Vis Sci. 2002 Dec;43(12):3712-6.

Abstract

Purpose: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Infective Agents, Local / immunology
  • Anti-Infective Agents, Local / therapeutic use*
  • Antibody Formation / immunology
  • Colony Count, Microbial
  • Corneal Stroma / microbiology
  • Endophthalmitis / immunology
  • Endophthalmitis / microbiology
  • Endophthalmitis / therapy
  • Enzyme-Linked Immunosorbent Assay
  • Eye Infections, Bacterial / immunology
  • Eye Infections, Bacterial / microbiology
  • Eye Infections, Bacterial / therapy*
  • Immunity
  • Immunization
  • Immunoglobulin G / blood
  • Immunotherapy*
  • Keratitis / immunology
  • Keratitis / microbiology
  • Keratitis / therapy
  • Lysostaphin / immunology
  • Lysostaphin / therapeutic use*
  • Methicillin / pharmacology
  • Methicillin Resistance*
  • Rabbits
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / therapy*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / isolation & purification*
  • Vitreous Body / microbiology

Substances

  • Anti-Infective Agents, Local
  • Immunoglobulin G
  • Lysostaphin
  • Methicillin