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

Antimicrob Agents Chemother. 2021 Mar 18;65(4):e01840-20. doi: 10.1128/AAC.01840-20. Print 2021 Mar 18.

Abstract

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. 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.

Keywords: MRSA; biofilms; gentamicin; implanted devices; local delivery; osteomyelitis; vancomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Gentamicins
  • Humans
  • Hyaluronic Acid
  • Hydrogels
  • Methicillin-Resistant Staphylococcus aureus*
  • Sheep
  • Staphylococcal Infections* / drug therapy
  • Vancomycin

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Hydrogels
  • Vancomycin
  • Hyaluronic Acid