A Review of Phage Therapy for Bone and Joint Infections

Ferry, Tristan

doi:10.1007/978-1-0716-3523-0_14

Cited by 2 publications

(6 citation statements)

References 60 publications

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“…Regardless of the phage phylogeny, the life cycle of phage-host interaction is similar, with viral attachment, penetration, replication, and release leading to bacterial death and multiplication of phage particles (Fig. 1A and B) (16,17).…”

Section: Basic Sciencementioning

confidence: 99%

“…Since phage therapy has been shown to support improved outcomes in MSI, the preclinical and basic science fields have continued to pursue improvements in treatment efficacy (16,17,18,19,20,21). In addition, efforts to commercialise and translate phage therapy to a wider patient population have also been a driving factor for innovation in phage therapy.…”

Section: Basic Sciencementioning

confidence: 99%

“…Another important limitation of phage therapy, particularly when considering industrial scale-up and clinical implementation, is the host range of any given phage or phage cocktail. Currently, selectivity of phages against bacterial hosts is determined by the phage receptor-binding proteins and their specificity for receptors on the bacterial surface (16,17). Classically, this is considered a positive attribute, as it limits offtarget effects of phage application on other species within the microbiome.…”

Section: Basic Sciencementioning

confidence: 99%

“…From one-shot administration of phage therapy during conservative surgery to exclusive intravenous injections, several modes of administration have been described. Ferry et al described the PhagoDAIR procedure in 2020, and since then, different treatment modalities for the treatment of complex PJI have been standardised through the PHAGEinLYON Clinic programme (supported by the Hospices Civils de Lyon Foundation) and based on the patient's medical history and clinical presentation (17,48). A national multidisciplinary team meeting, funded by the French health care ministry, has been set up at CRIOAc Lyon (https://www.crioac-lyon.fr) to determine if there is an indication for phage therapy in patients with complex MSI, and if yes, another dedicated multidisciplinary team meeting determines which phages would be the most appropriate and thereafter propose a personalised way of administration, depending on the clinical presentation.…”

Section: Periprosthetic Joint Infectionmentioning

confidence: 99%

“…For non-surgical patients, exclusive injections under sonography are proposed, and an intensive regimen has been set up with injections each Monday-Wednesday-Friday under sonography for 3 weeks (totalling 9 injections). Intravenous injections of phages for 1-3 weeks can be applied in nonsurgical patients with abscesses (17), also in combination with antibiotics.…”

Section: Periprosthetic Joint Infectionmentioning

confidence: 99%

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Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application

Ferry,

Onsea,

Roussel-Gaillard

et al. 2024

EFORT Open Reviews

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The treatment of musculoskeletal infections (MSIs), including periprosthetic joint infection (PJI) and fracture-related infection (FRI), is often complicated by biofilm-related challenges necessitating multiple revision surgeries and incurring substantial costs. The emergence of antimicrobial resistance (AMR) adds to the complexity of the problem, leading to increased morbidity and healthcare expenses. There is an urgent need for novel antibacterial strategies, with the World Health Organization endorsing non-traditional approaches like bacteriophage (phage) therapy. Phage therapy, involving the targeted application of lytic potent phages, shows promise in the treatment of MSIs. Although historical clinical trials and recent case studies present significant milestones in the evolution of phage therapy over the past century, challenges persist, including variability in study designs, administration protocols and phage selection. Efforts to enhance treatment efficacy consist of personalized phage therapy and combination with antibiotics. Future perspectives entail addressing regulatory barriers, standardizing treatment protocols, and conducting high-quality clinical trials to establish phage therapy’s efficacy for the treatment of MSIs. Initiatives like the PHAGEFORCE study and the PHAGEinLYON Clinic programme aim to streamline phage therapy, facilitating personalized treatment approaches and systematic data collection to advance its clinical utility in these challenging infections.

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Section: Basic Sciencementioning

confidence: 99%

Section: Basic Sciencementioning

confidence: 99%

Section: Basic Sciencementioning

confidence: 99%

Section: Periprosthetic Joint Infectionmentioning

confidence: 99%

Section: Periprosthetic Joint Infectionmentioning

confidence: 99%

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Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application

Ferry,

Onsea,

Roussel-Gaillard

et al. 2024

EFORT Open Reviews

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Case report: Local bacteriophage therapy for fracture-related infection with polymicrobial multi-resistant bacteria: hydrogel application and postoperative phage analysis through metagenomic sequencing

Alt,

Gessner,

Merabishvili

et al. 2024

Front. Med.

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Fracture-related infections can be challenging, particularly with concomitant severe bone defects and multi-resistant microorganisms. We present a case of a 42-year-old patient with a fracture-related infection following a war injury from a gunshot, resulting in a 12-cm subtrochanteric segmental bone defect and the detection of four different multi-resistant Gram-negative bacteria. Due to antibiotic drug resistance, treatment with bacteriophages was considered. Phage susceptibility testing revealed the activity of a commercially available bacteriophage cocktail (Intesti bacteriophage, Eliava Institute, Tbilisi, Georgia). This phage cocktail was included in a modified two-stage Masquelet technique. During the first intervention, the bone was debrided and samples for microbiological and phage testing were harvested. The indwelling intramedullary rod was removed, and the bone defect was filled with a PMMA spacer loaded with colistin and the bone stabilized with a plate. During the second procedure, the PMMA spacer was removed and a silver-coated angular stable plate was implanted. The bone defect was filled with a fibular autograft and allograft cancellous bone chips. At the end of the procedure, the Intesti bacteriophage cocktail was injected into a DAC hydrogel and this bacteriophage hydrogel composite was then put onto the angular stable plate. Postoperatively the wound fluid was collected over 72 h, and high-throughput metagenomic sequencing was performed. This showed a time-dependent release of the bacteriophages in the wound fluid, with a relatively high concentration after 12 h, decreasing to DNA copies of 0 after 72 h. Furthermore, we have assessed the release of phages from DAC gel and the effect of DAC gel on the phages in vitro. The results showed a stable and rapid release of phages from the DAC gel (~1×103 PFU/mL). The clinical course of the patient showed no relapse of the infection with good bone consolidation of the bone defect after 1 year without the need for any surgical revision. To the best of our knowledge, this is the first case that shows the detection of bacteriophage DNA copies by high-throughput metagenomics sequencing in a patient with a complex fracture-related infection. Successful treatment of this case encourages further investigation of bacteriophage therapy in patients with complex bone and joint infections.

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A Review of Phage Therapy for Bone and Joint Infections

Cited by 2 publications

References 60 publications

Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application

Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application

Case report: Local bacteriophage therapy for fracture-related infection with polymicrobial multi-resistant bacteria: hydrogel application and postoperative phage analysis through metagenomic sequencing

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