JAC Advance Access originally published online on September 10, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):1051-1059; doi:10.1093/jac/dkm347
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Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model
Biosynexus Incorporated, 9298 Gaither Rd, Gaithersburg, MD 20877, USA
Received 11 April 2007; returned 5 June 2007; revised 13 August 2007; accepted 14 August 2007
* Correspondence address. Tel: +1-301-987-1172; Fax: +1-301-944-2141; E-mail: johnkun{at}biosynexus.com
Objectives: With the isolation of clinical strains of Staphylococcus aureus carrying the gene that confers vancomycin resistance, the need for novel antistaphylococcals has become more urgent. Lysostaphin, an example of such a novel therapeutic, is an endopeptidase that rapidly lyses S. aureus through proteolysis of the staphylococcal cell wall. We evaluated its efficacy as a therapeutic agent for treatment of systemic S. aureus infection in a mouse model.
Methods: Mice (5–10 per group) challenged with methicillin-susceptible S. aureus developed bacteraemia and organ infections while mice challenged with methicillin-resistant S. aureus (MRSA) developed organ infections. The challenged mice received various intravenous doses of recombinant lysostaphin, administered once a day for 1–3 days when compared with treatment with oxacillin or vancomycin. Some mice also received treatment of lysostaphin combined with oxacillin or vancomycin. Following treatment, bacteraemia was determined, and mice were sacrificed and organ infection was determined.
Results and conclusions: Lysostaphin administered at 5 mg/kg once a day for 3 days consistently cleared S. aureus from the blood and the organs of infected mice. Furthermore, the combination of lysostaphin and oxacillin or vancomycin demonstrated increased efficacy against MRSA over lysostaphin alone allowing the therapeutic dose of lysostaphin to be reduced to 1 mg/kg. These results demonstrate that lysostaphin is an effective treatment for eradicating S. aureus from the blood and from the organs of infected mice.
Keywords: oxacillin , vancomycin , dosing regimen
Present address. National Institutes of Health, Bethesda, MD, USA.
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