JAC Advance Access originally published online on April 27, 2009
Journal of Antimicrobial Chemotherapy 2009 64(1):94-100; doi:10.1093/jac/dkp145
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Original research |
Lysostaphin eradicates established Staphylococcus aureus biofilms in jugular vein catheterized mice
Biosynexus Incorporated, 9298 Gaither Rd, Gaithersburg, MD 20877, USA
Received 5 January 2009; returned 16 March 2009; revised 20 March 2009; accepted 31 March 2009
* Corresponding author. Tel: +1-301-987-1172; Fax: +1-301-944-2141; E-mail: johnkun{at}biosynexus.com
Objectives: Staphylococcus aureus infections associated with indwelling devices can be very difficult to treat due to the recalcitrant nature of bacterial biofilms to conventional antibiotics. Lysostaphin has been shown to clear S. aureus biofilms in vitro, and in this study we determined whether lysostaphin could also eradicate established S. aureus biofilms on implanted jugular vein catheters in mice.
Methods: Jugular vein catheterized mice (four to six per group) challenged with S. aureus developed multiorgan infection and biofilm infections on the catheters. The infected mice with established biofilms received various doses of recombinant lysostaphin through the catheters, administered up to three times daily for up to 4 days. Some mice also received lysostaphin combined with nafcillin. Following treatment, mice were sacrificed and cfu on the catheter and in the liver and heart were determined. In another set of experiments, implanted jugular vein catheters in mice were pre-instilled with lysostaphin to determine whether this pre-treatment would protect the mice from biofilm infection.
Results and conclusions: Lysostaphin administered at 15 mg/kg in combination with 50 mg/kg nafcillin three times per day for 4 days eradicated established S. aureus, including methicillin-resistant S. aureus, biofilms from implanted catheters and sterilized heart and liver infections of S. aureus-infected mice. Furthermore, a single pre-instillation of 10 mg/kg lysostaphin in catheters completely protected catheterized mice from a subsequent biofilm infection. These results demonstrate that lysostaphin is an effective treatment as well as prophylaxis for S. aureus biofilms on indwelling catheters.
Keywords: MRSA , nafcillin , heart , liver , dosing regimen , pre-instillation
Present address: National Institutes of Health, NIDDK, Building 31, 31 Center Dr., Bethesda, MD 20892, USA.