A novel antibacterial compound decreases MRSA biofilm formation without the use of antibiotics in a murine model

Author:

Bouloussa Houssam1,Durand Zoe1,Gibon Emmanuel1ORCID,Chen Antonia F.2ORCID,Grant Matthew3,Saleh‐Mghir Azzam4,Mirza Mohsin1,Stutzman Bradley5,Vergari Claudio6ORCID,Yue James7,Anzala Nelson8,Bonnot Dorian8,Albac Sandrine8,Bouloussa Othman5,Croisier Delphine8

Affiliation:

1. DeBogy Molecular Inc. Farmington Connecticut USA

2. Department of Orthopaedic Surgery, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

3. Section of Infectious Diseases New Haven Connecticut USA

4. UVSQ‐Inserm, UMR 1173 Infection and Inflammation Montigny‐le‐Bretonneux France

5. Technology Incubation Program Farmington Connecticut USA

6. Arts et Métiers Sciences et Technologie Institut de Biomécanique Humaine Georges Charpak Paris France

7. CT Orthopaedic Specialists, Department of Surgery Frank H Netter School of Medicine Quinnipiac University North Haven Connecticut USA

8. Vivexia SARL Dijon France

Abstract

AbstractDespite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in vivo safety and antibacterial efficacy of titanium implants treated with a novel broad‐spectrum biocidal compound (DBG21) against methicillin‐resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21‐treated for 44 treated mice. After implantation, 1 × 107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were killed at 7 and 14 days to determine the number of adherent bacteria (biofilm) on implants and in the peri‐implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21‐treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU [99.97%] reduction [p < 0.001] and 1.9 median log10 CFU [98.7%] reduction [p = 0.037], respectively) and peri‐implant surrounding tissues (2.7 median log10 CFU/g [99.8%] reduction [p < 0.001] and 5.6 median log10 CFU/g [99.9997%] reduction [p < 0.001], respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG‐21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant‐related infections.

Publisher

Wiley

Subject

Orthopedics and Sports Medicine

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