Bacteriophages: sharing pharmaceutical experience around a clinical case
Hôpital Henri Mondor - Créteil
Phage therapy, an ancient therapy forgotten in our Western countries, consists of the administration of bacteriophages, virus that specifically infect a bacterial strain, for the treatment of infected patients at the end of their therapeutic options. At the moment, it does not have a regulatory framework.
Case of a 65-year-old patient with an osteo-articular infection with multi-resistant Streptocuccus dysgalactiae equisimilis and Staphylococcus aureus on a calcaneal stump, amputated for diabetic foot ulcers.
A request for a nominative Temporary Use Authorisation (ATU) is addressed to the National Drug Safety Agency (ANSM) but cannot be honored. The ANSM requires recent microbiological results and takes into account the pejorative clinical situation. In parallel, a request for compassionate treatment is made to the only industrial company involved in France: Pherecydes Pharma, which produces a phagogram (sensitivity test to available phages based on a bacteriological sample). Two strains of anti-staphylococcus aureus phages are active.
The pharmaceutical compounding is completed under medical and pharmaceutical responsibilities due to the absence of quality and industrial production standards, under sterile conditions. The entire contents of each 1 ml vial of phage should be administered to the patient after NaCl resuspension in an empty sterile bag. The total volume of the preparation is agreed with the physician according to the surface to be treated (here 30 ml). The preparation can be stored for 2 hours at room temperature. A file tracking the decrease in the concentration provides information on the last concentration known by the manufacturer.
Bio-decontamination of the biological safety cabinet before and after preparation; waste disposal via Waste from Infectious Risk Care Activities (DASRI).
Administration: First cycle J1 J3 then 2nd cycle 7 days later J1 J3 J6 applied locally and in osteo-articular injection.
The results were satisfactory in association with detersive gestures and antibiotic therapy, with harmonious wound budding after 5 administrations. The evolution was secondarily unfavourable following the discontinuation of tazocillin 3 days after the last phage administration. This led to a transtibial amputation 16 days after the last phage administration.
As a promising therapy, supported by the ANSM, phage therapy requires the definition of its precise indications and administration methods (rhythm, route, dose), after the completion of clinical trials (phagoburn completed, others to come). For the time being, a manufacturing laboratory in France is making available compassionate strains of anti-S. aureus and anti-P. aeruginosa, not industrially manufactured but of a quality compatible with clinical use, pending its ability to produce phages according to a qualified process that will allow the granting of ATU by the end of 2019.