Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella.

Gopala K Mannala, Markus Rupp, Nike Walter, Raphaelle Youf, Susanne B��rtl, Martijn Riool, Volker Alt
Author Information
  1. Gopala K Mannala: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID
  2. Markus Rupp: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID
  3. Nike Walter: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID
  4. Raphaelle Youf: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany.
  5. Susanne B��rtl: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID
  6. Martijn Riool: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID
  7. Volker Alt: Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany. ORCID

Abstract

Aims: Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in .
Methods: For the haematogenous infection, larvae were implanted with a Kirschner wire (K-wire), infected with , and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses.
Results: In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models.
Conclusion: Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage implant-related infection, repetitive doses of the combination of phages and gentamicin are required.

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