Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model

• Published in: Journal of antimicrobial chemotherapy Vol. 60; no. 5; pp. 1051 - 1059
• Main Authors: Kokai-Kun, John F., Chanturiya, Tanya, Mond, James J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2007; Oxford Publishing Limited (England)
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteremia - drug therapy; Bacteremia - microbiology; Bacterial diseases; Biological and medical sciences; Chemotherapy; Dose-Response Relationship, Drug; dosing regimen; Drug resistance; Enzymes; Female; Human bacterial diseases; Infectious diseases; Kidney - microbiology; Liver - microbiology; Lysostaphin - therapeutic use; Medical sciences; Methicillin Resistance; Mice; Neutropenia; Neutrophils - microbiology; oxacillin; Pharmacology. Drug treatments; Rodents; Spleen - microbiology; Staphylococcal Infections - drug therapy; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus infections; vancomycin; oxacillin; vancomycin; dosing regimen; Animal model; Peptides; Metalloendopeptidases; Vancomycin; Posology; Penicillin derivatives; Oxacillin; Glycopeptide; Bacteria; Micrococcales; Micrococcaceae; Disseminated; Staphylococcus aureus; Enzyme; β-Lactams; Rodentia; Infection; Peptidases; Vertebrata; Antibiotic; Lysostaphin; Mammalia; Treatment; Mouse; Polypeptide; Bacteriosis; Hydrolases; Antibacterial agent; Staphylococcal infection
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkm347

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.