Phage Therapy and Bone Infections

"Doctor Dublanchet, 'Phage Therapy, Viruses to Fight Infections' pages 154 and 155"

Doctor Dublanchet has notably worked on the treatment of bone infections using phage therapy. He discusses ongoing studies and analyses on phage therapy and mentions some successful compassionate treatments.We invite you to read his very precise book. Georgians practice this on a daily basis, and in cases of bone and joint infections, as stipulated by Doctor Dublanchet, they always combine, where possible, antibiotic therapy and phage therapy with a very high success rate.

The following paragraphs are extracts from his book on the treatments of bone infections using phage therapy.

TREATMENT OF BONE INFECTIONS WITH PHAGE THERAPY

Ces types d’infection constituent un problème en constante augmentation et seraient une indication privilégiée de la phagothérapie. La première étude économico-épidémiologique d’importance a évalué qu’en France, en 2008, 28 453 patients étaient atteints d’une IOA, ce qui avait entraîné un coût direct de 259 millions d’Euros. Les échecs thérapeutiques (absence de réponse des traitements conventionnels bien conduits) ne sont pas rares et extrêmement coûteux pour la société.

De plus, du fait d’une invalidité très prolongée, source de problèmes socio-économiques majeurs, des surcoûts importants ne sont pas compatbilisés. L’utilisation de la Phagothérapie pourrait trouver une justification supplémentaire dans le fait que certains bactériophages sont inhibiteurs des biofilms. Or il a été montré que les biofilms sont des facteurs répresseurs des ostéoblastes : L’ostéoblaste correspond à la forme jeune de la cellule osseuse. Les ostéoblastes ont une origine mésenchymateuse, ils proviennent des cellules souches), qui sont les cellules qui participent à l’ostéosynthèse (technique chirurgicale de réparation des fractures).These types of infections are an increasingly growing problem and would be a favored indication for phage therapy. The first significant economic-epidemiological study estimated that in France, in 2008, 28,453 patients were affected by a bone and joint infection, which led to a direct cost of 259 million Euros. Therapeutic failures (lack of response from well-conducted conventional treatments) are not rare and extremely costly for society.

In addition, due to very prolonged disability, which leads to major socio-economic problems, significant additional costs are not accounted for. The use of phage therapy could find further justification in the fact that some bacteriophages inhibit biofilms. It has been shown that biofilms are repressive factors for osteoblasts (Definition of l’ostéoblast-Source wikipedia: Osteoblasts from the Greek combining forms for "bone", ὀστέο-, osteo- and βλαστάνω, blastanō "germinate") are cells with a single nucleus that synthesize bone), which are the cells that participate in osteosynthesis (surgical technique for repairing fractures).

Chances of Healing a Bone and Joint Infection with Phage Therapy

In the absence of material, while not easy to treat, bone and joint infections are probably the ones with the highest chance of healing under appropriate treatment. However, two major factors need to be considered: the poor diffusion of antibiotics in the bone and the significant frequency of antibiotic resistance (67%, 16%, and 16% respectively for staphylococci, Gram-negative bacteria, and streptococci).

S. aureus (golden staph) represents the bacteria most often involved in prolonged infections. The establishment of a biofilm by bacterial strains seems to be hindered by certain bacteriophages. Furthermore, an in vivo experimental study showed that the combination of debridement and bacteriophages would be an additional asset for a favorable outcome, especially in association with an antibiotic like gentamicin. Finally, the use of a fluorescent strain of S.aureus that has just been published will be a very useful tool for this type of study in animal models.

Phage Therapy on Joint Prostheses

Joint prostheses (hip, knee), which will become increasingly common with the aging of populations, get infected in about 2.5% of cases, predominantly with methicillin-resistant S. aureus (MRSA). Antibiotics poorly diffuse into bone tissue and as these are generally subacute or chronic infections, the formation of a biofilm on the material makes the action of antibiotics even more unlikely. The treatment of osteitis (or bone and joint infection) with material is heavy, prolonged, and requires, at least temporarily, the removal of the prostheses before treatment.

The use of bacteriophages that have a lytic activity on the bacteria and are capable of preventing, or even attacking, the biofilm, could avoid this inconvenience. We have made this bet, on a compassionate basis in some cases with success. Studies seem to confirm that this is probably not utopian... One study appears particularly demonstrative... It involves a model of bone infection in rats for two types of MRSA infection (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa... A very complete analysis concluded that appropriate phage therapy associated with appropriate antibiotic treatment could dissolve the biofilm for both bacterial species, with a more pronounced effect on the model with Staphylococcus aureus than on the one with Pseudomonas aeruginosa.

Quelles sont les conditions de réussite d'un traitement par phagothérapie

In the case of osteitis (or bone and joint infections), several factors significantly impact the outcome of phage therapy:
- Access to the infected site (fistula, wound, etc., which assist in the delivery of phages)
- Vascularization, which helps to effectively drain the blood, and hence, the immune system, to the infected site (especially in the legs)
- Diabetes, which can slow down the treatment's effectiveness
- The patient's immune system,
- AND MOST IMPORTANTLY, the bacteria responsible for the infection.
In the vast majority of cases, these are bacteria that phage therapy can easily treat: Staphylococcus aureus (golden staph), Pseudomonas, Staphylococcus epidermidis (white staph). However, there can be other bacteria for which phages have not yet been found or for which phage therapy does not work (especially intracellular bacteria).It is possible to verify the bacteria treatable by phage therapy by visiting the page "What does phage therapy treat?" “What does phage therapy treat ? To understand the treatment for Staphylococcus aureus, visit the page "How to treat Staphylococcus aureus."