4.7 Article

A Hyaluronic Acid Hydrogel Loaded with Gentamicin and Vancomycin Successfully Eradicates Chronic Methicillin-Resistant Staphylococcus aureus Orthopedic Infection in a Sheep Model

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 4, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01840-20

Keywords

MRSA; biofilms; gentamicin; implanted devices; local delivery; osteomyelitis; vancomycin

Funding

  1. AOTrauma as part of the Clinical Priority Program (CPP) Bone Infection [AR2016_09]

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The study introduces a clinically relevant large animal model of chronic MRSA ODRI, demonstrating that an injectable, thermoresponsive, hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment. These results suggest that local antibiotic delivery with an injectable hydrogel can significantly increase treatment success rates beyond current clinical practice in a robust animal model.
Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone to developing orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermoresponsive, hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. IV These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.

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