Combination Therapy With Lysin CF-301 and Antibiotic Is Superior to Antibiotic Alone for Treating Methicillin-Resistant Staphylococcus aureus–lnduced Murine Bacteremia

• Published in: The Journal of infectious diseases Vol. 209; no. 9; pp. 1469 - 1478
• Main Authors: Schuch, Raymond, Lee, Han M., Schneider, Brent C., Sauve, Karen L., Law, Christina, Khan, Babar K., Rotolo, Jimmy A., Horiuchi, Yuki, Couto, Daniel E., Raz, Assaf, Fischetti, Vincent A., Huang, David B., Nowinski, Robert C., Wittekind, Michael
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01-05-2014
• Subjects: Antibacterials; Antibiotics; Antimicrobials; Bacteremia; Bacteria; Biofilms; Infections; Methicillin resistant staphylococcus aureus; Mice; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613

Lysins are bacteriophage-derived enzymes that degrade bacterial peptidoglycans. Lysin CF-301 is being developed to treat Staphylococcus aureus because of its potent, specific, and rapid bacteriolytic effects. It also demonstrates activity on drug-resistant strains, has a low resistance profile, eradicates biofilms, and acts synergistically with antibiotics. CF-301 was bacteriolytic against 250 S. aureus strains tested including 120 methicillin-resistant S. aureus (MRSA) isolates. In time-kill studies with 62 strains, CF-301 reduced S. aureus by 3-log₁₀ within 30 minutes compared to 6-12 hours required by antibiotics. In bacteremia, CF-301 increased survival by reducing blood MRSA 100-fold within 1 hour. Combinations of CF-301 with vancomycin or daptomycin synergized in vitro and increased survival significantly in staphylococcal-induced bacteremia compared to treatment with antibiotics alone (P<.0001). Superiority of CF-301 combinations with antibiotics was confirmed in 26 independent bacteremia studies. Combinations including CF-301 and antibiotics represent an attractive alternative to antibiotic monotherapies currently used to treat S. aureus bacteremia.