SpringerLink
Log in

A Review of Phage Therapy for Bone and Joint Infections

  • Protocol
  • First Online:
Bacteriophage Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2734))

Abstract

There is a strong rationale for using phages in patients with bone and joint infections (BJIs). Indeed, specific phages can infect and replicate in bacterial pathogens and have also demonstrated their activity in vitro against biofilm produced by different bacteria. However, there is a high variability of the different clinical forms of BJI, and their management is complex and frequently includes surgery followed by the administration of antibiotics. Regardless of the availability of active phages, optimal ways of phage administration in patients with BJIs are unknown. Otherwise, all BJIs are not relevant for phage therapy. Except for diabetic foot infection, a BJI with bone exposure is potentially not a relevant indication for phage therapy. On the counterpart, prosthetic joint infections in patients for whom a multidisciplinary expert team judges a conservative approach as the best option to keep the patient’s function seem to be a relevant indication with the hypothesis that phage therapy could increase the rate of infection control. The ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA) was created in 2022. One century after the first use of phages as a therapy, the phage therapy 2.0 era, with the possibility to evaluate personalized phage therapy in modern medicine and orthopedic surgery, is just open.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
EUR 44.95
Price includes VAT (France)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 149.79
Price includes VAT (France)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
EUR 189.89
Price includes VAT (France)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Sulakvelidze A, Alavidze Z, Morris JG (2001) Bacteriophage therapy. Antimicrob Agents Chemother 45:649–659

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Rostøl JT, Marraffini L (2019) (Ph)ighting phages: how bacteria resist their parasites. Cell Host Microbe 25:184–194

    PubMed Central  Google Scholar 

  3. Ackermann H-W (2007) 5500 phages examined in the electron microscope. Arch Virol 152:227–243

    CAS  PubMed  Google Scholar 

  4. Ferry T, Kolenda C, Briot T et al (2021) Past and future of phage therapy and phage-derived proteins in patients with bone and joint infection. Viruses 13:2414

    CAS  PubMed Central  Google Scholar 

  5. Tagliaferri TL, Jansen M, Horz H-P (2019) Fighting pathogenic bacteria on two fronts: phages and antibiotics as combined strategy. Front Cell Infect Microbiol 9:22

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Lew DP, Waldvogel FA (2004) Osteomyelitis. Lancet 364:369–379

    CAS  PubMed  Google Scholar 

  7. Lemaignen A, Grammatico-Guillon L, Astagneau P et al (2020) Computerized registry as a potential tool for surveillance and management of complex bone and joint infections in France: French registry of complex bone and joint infections. Bone Joint Res 9:635–644

    PubMed  PubMed Central  Google Scholar 

  8. Ferry T, Seng P, Mainard D et al (2019) The CRIOAc healthcare network in France: a nationwide health ministry program to improve the management of bone and joint infection. Orthop Traumatol Surg Res 105:185–190

    PubMed  Google Scholar 

  9. Ferry T, Kolenda C, Briot T et al (2022) Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4 years’ experience. Clin Microbiol Infect 28:145–146

    PubMed  Google Scholar 

  10. Depypere M, Morgenstern M, Kuehl R et al (2020) Pathogenesis and management of fracture-related infection. Clin Microbiol Infect 26:572–578

    CAS  PubMed  Google Scholar 

  11. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint infections. N Engl J Med 351:1645–1654

    CAS  PubMed  Google Scholar 

  12. Andrianasolo J, Ferry T, Boucher F et al (2018) Pressure ulcer-related pelvic osteomyelitis: evaluation of a two-stage surgical strategy (debridement, negative pressure therapy and flap coverage) with prolonged antimicrobial therapy. BMC Infect Dis 18:166

    PubMed  PubMed Central  Google Scholar 

  13. Peltola H, Pääkkönen M (2014) Acute osteomyelitis in children. N Engl J Med 370:352–360

    CAS  PubMed  Google Scholar 

  14. Tande AJ, Patel R (2014) Prosthetic joint infection. Clin Microbiol Rev 27:302–345

    PubMed  PubMed Central  Google Scholar 

  15. Bjarnsholt T, Alhede M, Alhede M et al (2013) The in vivo biofilm. Trends Microbiol 21:466–474

    CAS  PubMed  Google Scholar 

  16. Virot E, Servien E, Laurent F et al (2015) Reactivation of Clostridium tertium bone infection 30 years after the Iran-Iraq war. BMJ Case Rep 2015:bcr2014209169

    PubMed  PubMed Central  Google Scholar 

  17. Zimmerli W, Sendi P (2017) Orthopaedic biofilm infections. APMIS 125:353–364

    PubMed  Google Scholar 

  18. Ferry T, Batailler C, Brosset S et al (2020) Medical innovations to maintain the function in patients with chronic PJI for whom explantation is not desirable: a pathophysiology-, multidisciplinary-, and experience-based approach. SICOT J 6:26

    PubMed  PubMed Central  Google Scholar 

  19. Ellington JK, Harris M, Hudson MC et al (2006) Intracellular Staphylococcus aureus and antibiotic resistance: implications for treatment of staphylococcal osteomyelitis. J Orthop Res 24:87–93

    PubMed  Google Scholar 

  20. Adnan M, Ali Shah MR, Jamal M et al (2020) Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm. Biologicals 63:89–96

    CAS  PubMed  Google Scholar 

  21. Amankwah S, Abdusemed K, Kassa T (2021) Bacterial biofilm destruction: a focused review on the recent use of phage-based strategies with other antibiofilm agents. Nanotechnol Sci Appl 14:161–177

    PubMed  PubMed Central  Google Scholar 

  22. Chegini Z, Khoshbayan A, Taati Moghadam M et al (2020) Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review. Ann Clin Microbiol Antimicrob 19:45

    PubMed Central  Google Scholar 

  23. Topka-Bielecka G, Dydecka A, Necel A et al (2021) Bacteriophage-derived depolymerases against bacterial biofilm. Antibiotics (Basel) 10:175

    CAS  PubMed  Google Scholar 

  24. Lu H, **ong W, Li Z et al (2021) Activity of the lyases LysSSE1 and HolSSE1 against common pathogenic bacteria and their antimicrobial efficacy in biofilms. Bioorg Chem 116:105322

    CAS  PubMed  Google Scholar 

  25. Souche A, Kolenda C, Teoli J et al (2022) Activity of Exebacase (CF-301) against biofilms formed by Staphylococcus epidermidis strains isolated from prosthetic joint infections. Antimicrob Agents Chemother 66:e0058822

    Google Scholar 

  26. Raven TF, Moghaddam A, Ermisch C et al (2019) Use of Masquelet technique in treatment of septic and atrophic fracture nonunion. Injury 50(Suppl 3):40–54

    PubMed  Google Scholar 

  27. Pelissier P, Masquelet AC, Bareille R et al (2004) Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res 22:73–79

    CAS  PubMed  Google Scholar 

  28. Ferguson J, Diefenbeck M, McNally M (2017) Ceramic biocomposites as biodegradable antibiotic carriers in the treatment of bone infections. J Bone Jt Infect 2:38–51

    PubMed Central  Google Scholar 

  29. Ramanathan D, Siqueira MB, Klika AK et al (2015) Current concepts in total femoral replacement. World J Orthop 6:919–926

    PubMed  PubMed Central  Google Scholar 

  30. Osmon DR, Berbari EF, Berendt AR et al (2013) Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 56:e1–e25

    PubMed  Google Scholar 

  31. Kak V, Chandrasekar PH (2002) Bone and joint infections in injection drug users. Infect Dis Clin N Am 16:681–695

    Google Scholar 

  32. Hartemann-Heurtier A, Senneville E (2008) Diabetic foot osteomyelitis. Diabetes Metab 34:87–95

    CAS  PubMed  Google Scholar 

  33. Gouliouris T, Aliyu SH, Brown NM (2010) Spondylodiscitis: update on diagnosis and management. J Antimicrob Chemother 65(Suppl 3):iii11–iii24

    CAS  PubMed  Google Scholar 

  34. Berbari EF, Kanj SS, Kowalski TJ et al (2015) 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 61:e26–e46

    PubMed  Google Scholar 

  35. Slopek S, Durlakowa I, Weber-Dabrowska B et al (1984) Results of bacteriophage treatment of suppurative bacterial infections. III. Detailed evaluation of the results obtained in further 150 cases. Arch Immunol Ther Exp 32:317–335

    CAS  Google Scholar 

  36. Raiga A (1932) Le Bactériophage et ses applications thérapeutiques. La Science Médicale Pratique, Paris

    Google Scholar 

  37. Kutateladze M (2015) Experience of the Eliava institute in bacteriophage therapy. Virol Sin 30:80–81

    PubMed  PubMed Central  Google Scholar 

  38. Miedzybrodzki R, Fortuna W, Weber-Dabrowska B, Górski A (2009) A retrospective analysis of changes in inflammatory markers in patients treated with bacterial viruses. Clin Exp Med 9:303–312

    PubMed  Google Scholar 

  39. Ferry T, Leboucher G, Fevre C et al (2018) Salvage Debridement, Antibiotics and Implant Retention (“DAIR”) with local injection of a selected cocktail of bacteriophages: is it an option for an elderly patient with relapsing Staphylococcus aureus prosthetic-joint infection? Open Forum Infect Dis 5:ofy269

    PubMed  PubMed Central  Google Scholar 

  40. Ferry T, Boucher F, Fevre C et al (2018) Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages. J Antimicrob Chemother 73:2901–2903

    CAS  Google Scholar 

  41. Gonda I (2006) Systemic delivery of drugs to humans via inhalation. J Aerosol Med 19:47–53

    CAS  PubMed  Google Scholar 

  42. Purohit TJ, Hanning SM, Wu Z (2018) Advances in rectal drug delivery systems. Pharm Dev Technol 23:942–952

    CAS  PubMed  Google Scholar 

  43. Briot T, Kolenda C, Ferry T et al (2022) Paving the way for phage therapy using novel drug delivery approaches. J Control Release S0168-3659(22):00283–00288

    Google Scholar 

  44. Dąbrowska K, Abedon ST (2019) Pharmacologically aware phage therapy: pharmacodynamic and pharmacokinetic obstacles to phage antibacterial action in animal and human bodies. Microbiol Mol Biol Rev 83:e00012–e00019

    PubMed  PubMed Central  Google Scholar 

  45. Onsea J, Soentjens P, Djebara S et al (2019) Bacteriophage application for difficult-to-treat musculoskeletal infections: development of a standardized multidisciplinary treatment protocol. Viruses 11:891

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Malik DJ, Sokolov IJ, Vinner GK et al (2017) Formulation, stabilisation and encapsulation of bacteriophage for phage therapy. Adv Colloid Interf Sci 249:100–133

    CAS  Google Scholar 

  47. Onsea J, Wagemans J, Pirnay JP et al (2020) Bacteriophage therapy as a treatment strategy for orthopaedic-device-related infections: where do we stand? Eur Cell Mater 39:193–210

    CAS  PubMed  Google Scholar 

  48. Łusiak-Szelachowska M, Zaczek M, Weber-Dąbrowska B et al (2014) Phage neutralization by sera of patients receiving phage therapy. Viral Immunol 27:295–304

    PubMed  PubMed Central  Google Scholar 

  49. Górski A, Dąbrowska K, Międzybrodzki R et al (2017) Phages and immunomodulation. Future Microbiol 12:905–914

    PubMed  Google Scholar 

  50. Berbari EF, Marculescu C, Sia I et al (2007) Culture-negative prosthetic joint infection. Clin Infect Dis 45:1113–1119

    PubMed  Google Scholar 

  51. Malekzadeh D, Osmon DR, Lahr BD et al (2010) Prior use of antimicrobial therapy is a risk factor for culture-negative prosthetic joint infection. Clin Orthop Relat Res 468:2039–2045

    PubMed  PubMed Central  Google Scholar 

  52. Pääkkönen M, Kallio MJT, Kallio PE, Peltola H (2013) Significance of negative cultures in the treatment of acute hematogenous bone and joint infections in children. J Pediatric Infect Dis Soc 2:119–125

    PubMed  Google Scholar 

  53. Morozova VV, Kozlova YN, Ganichev DA, Tikunova NV (2018) Bacteriophage treatment of infected diabetic foot ulcers. Methods Mol Biol 1693:151–158

    CAS  PubMed  Google Scholar 

  54. Stravinskas M, Horstmann P, Ferguson J et al (2016) Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: in vitro and clinical release studies. Bone Joint Res 5:427–435

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Onsea J, Post V, Buchholz T et al (2021) Bacteriophage therapy for the prevention and treatment of fracture-related infection caused by Staphylococcus aureus: a preclinical study. Microbiol Spectr 9:e0173621

    PubMed  Google Scholar 

  56. Nir-Paz R, Gelman D, Khouri A et al (2019) Successful treatment of antibiotic-resistant, poly-microbial bone infection with bacteriophages and antibiotics combination. Clin Infect Dis 69:2015–2018

    PubMed  Google Scholar 

  57. Sarr L, Dembélé B, Mouhamed D et al (2018) Chronic pandiaphysity with chronic osteomyelitis. SM J Orthop 1:1064

    Google Scholar 

  58. Pape HC, Zwipp H, Regel G et al (1995) Chronic diaphyseal osteomyelitis of long bones refractory to conventional therapy – benefits and risks of reaming of the femoral medullary cavity. Eur J Orthop Surg Traumatol 5:53–58

    CAS  PubMed  Google Scholar 

  59. Djebara S, Maussen C, De Vos D et al (2019) Processing phage therapy requests in a Brussels military hospital: lessons identified. Viruses 11:265

    PubMed  PubMed Central  Google Scholar 

  60. World Medical Association (2013) World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194

    Google Scholar 

  61. Ferry T, Kolenda C, Laurent F et al (2022) Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection. Nat Commun 13:4239

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Cano EJ, Caflisch KM, Bollyky PL et al (2021) Phage therapy for limb-threatening prosthetic knee Klebsiella pneumoniae infection: case report and in vitro characterization of anti-biofilm activity. Clin Infect Dis 73:e144–e151

    PubMed  Google Scholar 

  63. Doub JB, Johnson AJ, Nandi S et al (2023) Experience using adjuvant bacteriophage therapy for the treatment of 10 recalcitrant periprosthetic joint infections: a case series. Clin Infect Dis 76(3):e1463–e1466. https://doi.org/10.1093/cid/ciac694

    Article  PubMed  Google Scholar 

  64. Ferry T, Kolenda C, Briot T, et al. (2021) Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4 years’ experience. Clin Microbiol Infect S1198-743X(21)00556–5

    Google Scholar 

  65. Ferry T, Kolenda C, Batailler C et al (2020) Phage therapy as adjuvant to conservative surgery and antibiotics to salvage patients with relapsing S. Aureus prosthetic knee infection. Front Med 7:570572

    Google Scholar 

  66. Ferry T, Kolenda C, Batailler C et al (2021) Case report: arthroscopic “debridement antibiotics and implant retention” with local injection of personalized phage therapy to salvage a relapsing Pseudomonas aeruginosa prosthetic knee infection. Front Med (Lausanne) 8:569159

    PubMed  Google Scholar 

Download references

Acknowledgments

This chapter was written with the experience acquired for many years throughout the Lyon Bone and Joint Infection study group and the PHAGEinLYON study group. The author acknowledges all the following colleagues belonging to these groups:

Lyon Bone and Joint Infection Study Group

Coordinator: Tristan Ferry

Infectious Diseases Specialists: Tristan Ferry, Florent Valour, Thomas Perpoint, Florence Ader, Sandrine Roux, Agathe Becker, Claire Triffault-Fillit, Anne Conrad, Cécile Pouderoux, Pierre Chauvelot, Paul Chabert, Clément Javaux, Johanna Lippman, Evelyne Braun;

Surgeons: Sébastien Lustig, Elvire Servien, Cécile Batailler, Stanislas Gunst, Axel Schmidt, Eliott Sappey-Marinier, Gaspard Fournier, Etienne Deroche, Robin Canetti, Michel-Henry Fessy, Anthony Viste, Jean-Luc Besse, Philippe Chaudier, Lucie Louboutin, Marcelle Mercier, Vincent Belgaid, Anouk Rozinthe, Tristan De Leissegues, Aram Gazarian, Arnaud Walch, Christophe Gaillard, Antoine Bertani, Frédéric Rongieras, Sébastien Martres, Franck Trouillet, Cédric Barrey, Ali Mojallal, Mathilde Lherm, Sophie Brosset, Hélène Person, Caroline Ospital, Philippe Céruse, Carine Fuchsmann, Arnaud Gleizal, Clémentine Daveau;

Anesthesiologists: Frédéric Aubrun, Mikhail Dziadzko, Caroline Macabéo, Dana Patrascu, Audrey Chevreau-Ciliberti;

Microbiologists: Frederic Laurent, Laetitia Beraud, Tiphaine Roussel-Gaillard, Céline Dupieux, Camille Kolenda;

Imaging: Fabien Craighero, Loic Boussel, Jean-Baptiste Pialat, Isabelle Morelec;

PK/PD specialists: Michel Tod, Marie-Claude Gagnieu, Sylvain Goutelle, Romain Garreau;

Clinical research assistant and database manager: Johanna Boulant

PHAGEinLYON Clinic Study Group

Coordinator: Tristan Ferry

Tristan Ferry, Myrtille Le Bouar, Thomas Briot, Gilles Leboucher, Camille Kolenda, Tiphaine Roussel-Gaillard.

Author information

Authors and Affiliations

  1. Service de Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

    Tristan Ferry

  2. Université Claude Bernard Lyon 1, Villeurbanne, France

    Tristan Ferry

  3. Centre de Références des IOA Complexes de Lyon, CRIOAc Lyon, Lyon, France

    Tristan Ferry

  4. StaPath team, Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France

    Tristan Ferry

  5. Education and Clinical Officer of the ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA), Basel, Switzerland

    Tristan Ferry

Authors
  1. Tristan Ferry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tristan Ferry .

Editor information

Editors and Affiliations

  1. Centre of Biological Engineering, University of Minho, Braga, Portugal

    Joana Azeredo

  2. International Iberian Nanotechnology Laboratory, Braga, Portugal

    Sanna Sillankorva

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Ferry, T. (2024). A Review of Phage Therapy for Bone and Joint Infections. In: Azeredo, J., Sillankorva, S. (eds) Bacteriophage Therapy. Methods in Molecular Biology, vol 2734. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3523-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-3523-0_14

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3522-3

  • Online ISBN: 978-1-0716-3523-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation