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

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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.

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Journal

Journal ID (iso-abbrev): Antimicrob Agents Chemother

Title: Antimicrobial agents and chemotherapy

Publisher: American Society for Microbiology

ISSN (Electronic): 1098-6596

ISSN (Print): 0066-4804

Publication date (Electronic): June 17 2021

Volume: 65

Issue: 7

Affiliations

[1 ] Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

[2 ] Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.

[3 ] Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France.

[4 ] CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France.

[5 ] Translational Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.

[6 ] Discovery Microbiome, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.

Article

Publisher Item ID: AAC.01832-20

DOI: 10.1128/AAC.01832-20

PMC ID: 8218614

PubMed ID: 33903108

SO-VID: 7aca7c54-3cb2-457c-b7b8-52601453bbcb

History

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

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

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

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Decoding Infection and Transmission

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