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Joseph J. Dajcs, Emma B. H. Hume, Judy M. Moreau, Armando R. Caballero, Bennetta M. Cannon, Richard J. O’Callaghan; Lysostaphin Treatment of Methicillin-Resistant Staphylococcus aureus Keratitis in the Rabbit. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1432-1437.
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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 treated topically every 30 minutes from 4 to
9 or 10 to 15 hours postinfection with 0.28% lysostaphin or 5.0%
vancomycin. Rabbits were killed and corneas were excised and cultured
to determine the number of colony forming units (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
hours postinfection) lysostaphin sterilized all MRSA 301–infected
corneas, whereas untreated corneas contained 6.52 log CFU/cornea
(P ≤ 0.0001). Corneas infected with MRSA 301 and
treated similarly with vancomycin retained 2.3 ± 0.85 log
CFU/cornea, and none were sterile. When therapy was begun later (10–15
hours postinfection) the residual bacteria in lysostaphin-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 ≤ 0.0001). Three experiments were performed to
demonstrate that lysostaphin penetrated the cornea to kill bacteria in
vivo; lysostaphin-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 observed therapeutic values of
conclusions. Lysostaphin is very effective in treating keratitis mediated by
methicillin-sensitive or methicillin-resistant S.
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