https://trustmyscience.com/un-traitement-a-base-de-virus-tueurs-de-bacteries-a-sauve-la-vie-dune-adolescente/
Un traitement à base de virus tueurs de bactéries a sauvé la vie d’une adolescente
Jean Jerrold Pierre
La majorité des phages ne sont pas autant efficaces que les médicaments conventionnels, car ils se contentent la plupart du temps de rester en état de dormance après avoir infecté leur hôte. Ce traitement est également inefficace contre les bactéries se cachant dans les cellules, car les bactériophages ne peuvent y pénétrer.
De plus, la plupart des recherches publiées dans ce domaine avaient été réalisées sans groupes de contrôle,
Citation : Le cas Patterson
Après avoir passé plusieurs mois à analyser dans leur collection de potentiels phages candidats, ils en ont sélectionnés 3 auxquels ils ont donné des noms : Muddy, ZoeJ et BPs. Le premier est naturellement très agressif contre les mycobactéries, tandis que les deux autres, qui ont tendance à rester en état de dormance une fois à l’intérieur de leur hôte, ont dû être modifiés génétiquement par les chercheurs.
Malgré ces quelques inconvénients mentionnés plus haut, la phagothérapie a l’avantage de pouvoir cibler l’agent infectieux désiré avec une très faible toxicité, comparé aux antibiotiques, qui peuvent également être mortels pour le microbiome, qui joue des rôles essentiels pour notre organisme.
La source : Revue Nature
Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus Rebekah M. Dedrick Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA

The patient was chronically infected with Pseudomonas aeruginosa and M. abscessus subspecies massiliense and had been on anti-NTM treatment for 8 years prior to lung transplantation.
After an uncomplicated bilateral lung transplant, immunosuppres-sive drugs and multiple intravenous (i.v.) antibiotics were adminis-tered (Extended Data Fig. 1). Severe side effects including nausea, anorexia, diarrhea, and electrolyte derangement necessitated total parenteral nutrition and discontinuation of i.v. antibiotics. Within 1 week of stopping intravenous therapy, redness was noted at the surgical incision. The chest X-ray showed consolidation, and M. abscessus grew from sputum
We exploited a collection of >10,000 phages isolated using Mycobacterium smegmatis by students in the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES)
Screening of a representa-tive subset identified one (Muddy) that kills GD01 efficiently (Fig. 2a and Supplementary Table 2). A second phage, ZoeJ, infects GD01 with reduced efficiency of plating (EOP), although the plaques are extremely turbid and difficult to visualize (Fig. 2a). A lytic deriva-tive of ZoeJ was engineered using Bacteriophage Recombineering of Electroporated DNA (BRED)17 to precisely remove its repressor gene (45);18 this efficiently infects and kills GD01 (Fig. 2a). A third phage (BPs) and its lytic derivative (BPsΔ33HTH)19 infect GD01 poorly, but we isolated host range mutants (HRM1 and HRM10) that infect GD01 efficiently and retain M. smegmatis infection (Fig. 2a and Supplementary Information). HRM1 and HRM10 have single base changes in the portal gene 3 (C2083T and A2695G) con-ferring R66W and N270D amino acid substitutions, respectively.
Brief CommuniCationNAturE MEDIcINETable 2). Thus, phages for GD01 are uncommon, but can be identi-fied with extensive searches. A search for phages of a second strain (M. abscessus GD02) from a clinically similar patient identified few useful phages (Supplementary Table 3); this patient subsequently died. Muddy, BPs, and ZoeJ do not kill other M. abscessus clinical isolates efficiently, and the three-phage cocktail is not a generaliz-able treatment (Fig. 2d).
After challenging a larger GD01 culture with the cocktail, some survivors were recovered and shown to be resistant to BPs33ΔHTH-HRM10 and ZoeJΔ45 but at least partially sensitive to Muddy
Twenty-four hours following a single topical test dose in the ster-nal wound, i.v. therapy was initiated with the three-phage cocktail (109 plaque forming units (PFU) per dose of each phage) every 12 h for at least 32 weeks
During the first 2 d of treatment, the patient felt sweaty and flushed but had no fever or changes on physical examination. Otherwise phage treatment was well tolerated throughout, without significant side effects. After 9 d, the patient was discharged and 12 h i.v. administration of the cock-tail was continued. After 1 month of treatment, the sternal wound, which had received a topical test dose, had improved more than the other skin lesions and topical daily phage therapy was commenced for both. Over the next 6 months (to the time of writing) the patient continued to improve clinically with gradual healing of surgical wound and skin lesions (Fig. 1d) and improvement of lung func-tion (Fig. 1a) and liver function. Weight increase was also observed, despite cessation of overnight supplemental feedings. A repeat CT-PET scan 6 weeks into phage treatment showed resolution of FDG activity of the previously enlarged node at the porta hepatis, although sternal and skin lesion activity remained (Fig. 1b–d).M. abscessus was not isolated from serum or sputum at any point after initiation of phage treatment, although M. abscessuswas cultured from swabs of slowly resolving skin nodules at 1, 3, 4, and 5 months. Sera showed no evidence of phage neutralization, although weak antibody responses to phage proteins were seen (Extended Data Fig. 4). Among the weak cytokine responses were interferon-γ (IFNγ), interleukin-6 (IL-6) and IL-10 after 16 d of treatment, tumour necrosis factor-α (TNFα), IL-6 and IL-10 after 1 month of treatment, and IL-6 after 3 and 4 months of treatment
Phage treatment was associated with clinical improvement, although we cannot exclude the possibility that patient gains would have occurred without phage treatment.
However, we note that patients with similar clinical conditions typically have high mor-bidity and mortality, that improvement was not temporally associ-ated with cessation or initiation of other drug administrations, and we show evidence to support in vivo phage replication. There were no adverse reactions to phage administration. We note that there is substantial variation in M. abscessus phage susceptibilities, and phage treatment of similar patients will require expansion of our understanding of phage infection of these strains.

https://edition.cnn.com/2019/05/09/health/cystic-fibrosis-teen-engineered-bacteriophage-study/index.html
Nina Avramova and Susan Scutti, CNN
When her doctors discontinued the intravenous antibiotics that caused Isabelle severe side effects, the bacterial infection that had plagued her for years returned with a vengeance. Her surgical incisions turned vibrant red.
« I know that because of the experience that I’ve had with other patients who have had a transplant and who were infected with MB, » Spencer said. « All of those patients went on and died. »
« It was actually the patient’s mum, Jo, who asked me about phage therapy, » she said.
« Cocktails of phages were used therapeutically in Europe and the United States during the pre-antibiotic era, and they are still prevalent in Russia and Central and Eastern Europe today, for wound infections, gastroenteritis, sepsis and other ailments, » wrote Charles Schmidt, a science writer, in a related article published in the journal Nature Biotechnology.
Luckily, Spencer said, « one of our microbiologist consultants here did his thesis on phage therapy 20 years ago. » Offering advice on Isabelle’s case, « he, by chance, knew a phage scientist in the [United] States, Graham Hatfull. »
A conference call between Spencer’s and Hatfull’s teams included Robert Schooley, an infectious-disease specialist who heads a phage translational research center at the University of California, San Diego, who « happened to be visiting Graham on the same day, so he came in on that same conversation. »
« Even as companies move toward clinical trials, they’re confronting entrenched biases against phage therapy by physicians inclined to view it as an old Soviet technology that was never backed by reliable evidence, » he wrote.