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Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit
J J Dajcs1, E B Hume, J M Moreau
1Department of Microbiology, Immunology, and Parasitology, LSU Medical Center in New Orleans, LA 70112, USA.
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 < or = 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 < or = 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 lysostaphin.
Conclusions:
Lysostaphin is very effective in treating keratitis mediated by methicillin-sensitive or methicillin-resistant S. aureus.
Insights
Lysostaphin effectively treats Staphylococcus aureus keratitis, including MRSA. Early and late topical lysostaphin treatment sterilized or significantly reduced bacterial load in rabbit corneas compared to vancomycin.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Microbiology
Background:
- Staphylococcus aureus, including methicillin-resistant strains (MRSA), is a common cause of bacterial keratitis.
- Current treatments may have limitations in efficacy against resistant strains.
Purpose of the Study:
- To evaluate the efficacy of topical lysostaphin in treating experimental Staphylococcus aureus keratitis in a rabbit model.
- To compare lysostaphin's effectiveness against both methicillin-sensitive and methicillin-resistant S. aureus (MRSA).
Main Methods:
- Compared lysostaphin and vancomycin sensitivity against MRSA and methicillin-sensitive strains.
- Induced keratitis in rabbit corneas using MRSA or a low-virulence strain.
- Administered topical lysostaphin or vancomycin at different time points post-infection.
- Quantified bacterial load (CFU/cornea) after treatment.
Main Results:
- Lysostaphin demonstrated significantly lower minimal inhibitory concentrations than vancomycin.
- Early lysostaphin therapy (4-9 hours post-infection) sterilized MRSA-infected corneas.
- Late lysostaphin therapy (10-15 hours post-infection) resulted in significantly lower residual bacterial counts compared to vancomycin.
- Experiments confirmed lysostaphin's corneal penetration and in vivo efficacy.
Conclusions:
- Lysostaphin is a highly effective treatment for keratitis caused by both methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
- Topical lysostaphin shows promise as a therapeutic agent for bacterial keratitis.