Efficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in Mice

Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00346-19. doi: 10.1128/AAC.00346-19. Print 2019 Aug.

Abstract

Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy compared with control antibody plus vancomycin in two mouse models of S. aureus SSI. Therefore, monoclonal antibody-based neutralization of multiple S. aureus virulence factors may provide an adjunctive perioperative approach to combat S. aureus SSIs.

Keywords: ClfA; MRSA; Staphylococcus aureus; alpha-toxin; clumping factor A; hla; leukocidin; surgical.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Bacterial Proteins / immunology
  • Broadly Neutralizing Antibodies / pharmacology
  • Coagulase / immunology
  • Leukocidins / immunology
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Surgical Wound Infection / drug therapy*
  • Surgical Wound Infection / microbiology
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bacterial Proteins
  • Broadly Neutralizing Antibodies
  • ClfA protein, Staphylococcus aureus
  • Coagulase
  • Leukocidins
  • leukocidin S-component protein, Staphylococcus
  • LukF protein, Staphylococcus aureus
  • suvratoxumab
  • Vancomycin