title: Combination therapy with lysin CF-301 and antibiotic is superior to antibiotic alone for treating methicillin-resistant Staphylococcus aureus-induced murine bacteremia.
abstract: 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.
authors.affiliation: ContraFect Corporation, Yonkers, NY.
authors.forename: Raymond
authors.initials: R
authors.lastname: Schuch
authors.forename: Han M
authors.initials: HM
authors.lastname: Lee
authors.forename: Brent C
authors.initials: BC
authors.lastname: Schneider
authors.forename: Karen L
authors.initials: KL
authors.lastname: Sauve
authors.forename: Christina
authors.initials: C
authors.lastname: Law
authors.forename: Babar K
authors.initials: BK
authors.lastname: Khan
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Rotolo
authors.forename: Yuki
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Couto
authors.forename: Assaf
authors.initials: A
authors.lastname: Raz
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
authors.forename: David B
authors.initials: DB
authors.lastname: Huang
authors.forename: Robert C
authors.initials: RC
authors.lastname: Nowinski
authors.forename: Michael
authors.initials: M
authors.lastname: Wittekind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D018441:Biofilms; D004357:Drug Synergism; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000737:chemistry / Q000494:pharmacology*; D039002:Prophages / Q000201:enzymology / Q000235:genetics; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014764:Viral Proteins / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D009088:Mucoproteins; D014764:Viral Proteins; C010393:lysin, gastropoda
keywords: MRSA; Staphylococcus aureus; bacteremia; daptomycin; lysin; vancomycin