Multimechanistic Monoclonal Antibody Combination Targeting Key Staphylococcus aureus Virulence Determinants in a Rabbit Model of Prosthetic Joint Infection

Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0183220. doi: 10.1128/AAC.01832-20. Epub 2021 Jun 17.

Abstract

In a rabbit model of methicillin-resistant Staphylococcus aureus prosthetic joint infection (PJI), prophylaxis with AZD6389*-a combination of three monoclonal antibodies targeting alpha-hemolysin, bicomponent cytotoxins (LukSF/LukED/HlgAB/HlgCB), and clumping factor A-resulted in significant reductions in joint swelling, erythema, intra-articular pus, and bacterial burden in synovial tissues and biofilm-associated prosthetic implants compared with isotype-matched control IgG. Targeting specific staphylococcal virulence factors may thus have potential clinical utility for prevention of PJI.

Keywords: Staphylococcus aureus; alpha-toxin; clumping factor A; leukocidin; monoclonal antibody; prosthetic joint infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Methicillin-Resistant Staphylococcus aureus*
  • Prostheses and Implants
  • Rabbits
  • Staphylococcal Infections* / drug therapy
  • Staphylococcus aureus
  • Virulence
  • Virulence Factors

Substances

  • Antibodies, Monoclonal
  • Virulence Factors