Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections
Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10<sup>3</sup> PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.
Authors
- T. Fintan Moriarty (ORCID: https://orcid.org/0000-0003-2307-0397)
- Luis Ponce Benavente
- Jolien Onsea (ORCID: https://orcid.org/0000-0002-5096-5789)
- Mercedes González Moreno (ORCID: https://orcid.org/0000-0003-3586-6544)
- Marco Chittò (ORCID: https://orcid.org/0000-0002-9813-9515)
- Caroline Constant (ORCID: https://orcid.org/0000-0002-7846-5612)
- Virginia Post (ORCID: https://orcid.org/0000-0003-4104-0044)
- Matteo D’Este (ORCID: https://orcid.org/0000-0002-0424-8172)
- Rob Lavigne (ORCID: https://orcid.org/0000-0001-7377-1314)
- Andrej Trampuž (ORCID: https://orcid.org/0000-0002-5219-2521)
- Stephan Zeiter (ORCID: https://orcid.org/0000-0002-8155-4202)
- Willem‐Jan Metsemakers (ORCID: https://orcid.org/0000-0002-4114-9093)
- Jeroen Wagemans (ORCID: https://orcid.org/0000-0002-2185-5724)
- R. Geoff Richards (ORCID: https://orcid.org/0000-0002-7778-2480)
- Pamela Nylund
- Baixing Chen (ORCID: https://orcid.org/0000-0002-4158-6816)
Institutions
- AO Foundation (CH)
- Humboldt-Universität zu Berlin (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
- KU Leuven (BE)
Publication Details
- Journal
- npj Biofilms and Microbiomes
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1038/s41522-024-00552-2
- Citations
- 14
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 6.42
Funders
- Joint Programming Initiative on Antimicrobial Resistance
- AO Foundation
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Vlaamse regering