WHO · alert
Top-10 global threat
The WHO ranks antibiotic resistance among the ten greatest threats to global public health.
WHO
Microbiology · precision therapeutics
Phage Therapy: A Targeted Approach to Antibiotic Resistance
The problem: when antibiotics are no longer enough
Antibiotic resistance is now recognised by the WHO as one of the top ten threats to global public health. In response, research has turned toward strategies that complement or offer alternatives to conventional antibiotics: bacteriophages, naturally occurring viruses that exclusively infect bacteria, are among the most actively studied avenues.
2019 mortality
1.27 million direct deaths
The Lancet (2022): 1.27 million deaths directly attributable to antimicrobial resistance, and nearly 5 million associated deaths.
AMR Collaborators, Lancet 2022
2050 projection
Over 39 million deaths
If current trends continue, more than 39 million cumulative deaths are expected by 2050.
Recent literature
Alternative avenues
Target rather than eradicate
Faced with this impasse, research is exploring strategies that complement antibiotics. Bacteriophages, natural viruses that infect only bacteria, are among the most studied.
The mechanism: how a phage destroys a bacterium
A bacteriophage follows a five-step cycle to destroy its target bacterium. The animation below walks through each step.
Animation interactive
Le cycle lytique d'un bactériophage
1
Adsorption
Le phage reconnaît et se fixe sur des récepteurs spécifiques présents à la surface de la bactérie cible, via les fibres de sa queue. Cette reconnaissance est extrêmement précise : un phage donné n'infecte généralement qu'une espèce, parfois une seule souche bactérienne.
Schéma basé sur Explor Drug Sci. 2025;3:1008133 et MedComm 2025 (PMC12256688). Représentation pédagogique simplifiée, à visée éducative uniquement.
Step 1
Adsorption
The phage recognises specific receptors on the surface of a particular bacterium and attaches to it. Specificity is very narrow: a given phage typically infects one species, sometimes a single strain.
Step 2
Genome injection
The phage punctures the bacterial cell wall and injects its genetic material inside, without entering the cell itself.
Step 3
Hijacking
The viral genome takes control of the cell, which begins producing the components needed to build new phages.
Step 4
Assembly
The viral components self-assemble into complete particles inside the infected bacterium.
Step 5
Lysis & release
Two viral enzymes, holin and endolysin, degrade the inner membrane and the cell wall (peptidoglycan). The bacterium bursts, releasing dozens to hundreds of new phages.
Strictly lytic phages only. Only these phages are selected for therapeutic use. A second family, known as temperate or lysogenic phages, integrate their genome into the bacterial genome without immediately destroying the cell (a dormant prophage state). This profile is excluded because it does not produce the desired bactericidal effect and can, in some cases, transfer genetic material between bacteria.
The core difference with an antibiotic: an antibiotic works through a broad-spectrum chemical mechanism that often indiscriminately affects many bacterial species, including those of the microbiome. A phage works through a physical, targeted destruction mechanism aimed at a single species, sometimes a single strain, without directly affecting the surrounding bacterial flora. This specificity explains the absence of cross-resistance with antibiotics.
History: a century of continuous practice, and a French comeback
Contrary to a claim sometimes repeated, the historical foundation of clinical phage therapy lies in Georgia and Poland. It is a French biologist, Félix d'Hérelle, who co-discovered bacteriophages in 1917, before the field was largely abandoned in the West in favour of antibiotics.
Georgia · 1923
Eliava Institute, Tbilisi
The world's oldest bacteriophage research and clinical centre, in continuous operation for a century. Specialities: internal medicine, urology, gynaecology, paediatrics. Patients from around the world.
Poland · 2005
Hirszfeld Institute, Wrocław
Phage Therapy Unit established under Prof. Andrzej Górski. Branches in Kraków and Częstochowa. One of the few European centres offering structured access to experimental phage therapy.
France · 2017→2026
PHAGEinLYON & PHAG-ONE
Programme led by Prof. Laurent and Prof. Ferry at the Hospices Civils de Lyon. On 28 May 2026, the ANSM granted the HCL a manufacturing authorisation for purified therapeutic phages: a first in France and the EU for a public institution.
HCL press release, 28 May 2026
The French pathway in detail. Since 2017, the PHAGEinLYON programme, led by Prof. Frédéric Laurent and Prof. Tristan Ferry at the Hospices Civils de Lyon (Croix-Rousse and Édouard Herriot hospitals), has been isolating, characterising and producing therapeutic phages on French soil. Phages are collected from the environment (notably wastewater), tested against the patient's bacterial strain, then assembled by a pharmacist into cocktails of two or three phages before administration, under the supervision of the French medicines agency (ANSM) and within a strictly compassionate-use framework.
In a letter dated 28 May 2026, the ANSM granted the HCL an authorisation to manufacture Pharmaceutical-Grade Raw Material (MPUP) for purified therapeutic phages, a first in France and in the European Union for a public healthcare institution. This authorisation paves the way for secure, GMP-compliant production, and for scaling toward a national phage therapy pathway carried by the PHAG-ONE project and the THERAPhage research hospital-university programme, both funded by the French National Research Agency.
The state of clinical research in 2025
The scientific literature has seen a notable acceleration recently.
Randomised trial · 2025
diSArm Phase IIa (AP-SA02)
First randomised demonstration of efficacy for intravenous phage therapy in complicated S. aureus bacteraemia. Day-12 clinical response: 88% (phage + ATB) vs 58% (placebo + ATB), p = 0.047.
IDWeek 2025 · Armata Pharmaceuticals
Meta-analysis · 2025
130 studies, 1,115 patients
Systematic review: promising clinical results for both personalised and standardised phage therapy, but only 9 randomised trials identified across the entire body of evidence.
Systematic review, ScienceDirect 2025
Ongoing trials
Gram-negative & bone infections
Chinese trial on ventilator-associated pneumonia (A. baumannii, P. aeruginosa, K. pneumoniae). In France, PHAGEinLYON cohort (NCT06185920): ~100 compassionate-use patients since 2017, enrolment through 2028.
Ferry et al., IJAA 2024
The most extensively studied pathogens remain Pseudomonas aeruginosa (hospital-acquired infections, cystic fibrosis) and Escherichia coli (multidrug-resistant urinary tract infections). In France, the Lyon team documented in 2024 (International Journal of Antimicrobial Agents) the implementation of its access programme since 2022, primarily for complex bone and joint infections linked to prosthetics or implants.
E. coli's role as a tool serving human health
Bio-engineering
From phage therapy to metabolic peptides
E. coli's role as a tool serving human health goes beyond phage therapy. The same bacterium, known for strains responsible for multidrug-resistant urinary tract infections, is also widely used as a production platform in bio-engineering. This is notably the case for GLP-1, the gut hormone at the heart of type 2 diabetes and weight-loss treatments (semaglutide), whose peptide sequence can be produced by fermentation of genetically modified E. coli strains.
Problem / Solution
One species, two faces
The same bacterial species sits both on the problem side (resistant infections) and on the solution side (production of therapeutic molecules), depending on the strain and context.
To explore GLP-1 and metabolic peptides further, head to our dedicated exploration.
Current limitations, worth knowing before any enthusiasm
Four points to keep in mind, to avoid confusing promise with everyday access.
French framework
Production authorised, access managed
Since 28 May 2026, the HCL manufacture under GMP. Phage therapy still has no conventional marketing authorisation: access remains compassionate-use, decided in multidisciplinary case review, under ANSM supervision. No public pathway, no outpatient prescription.
Outside compassionate use
Travel abroad
For patients who do not fall under French protocols (notably in Lyon), travel to the historic centres in Georgia or Poland remains a route documented in the literature.
Biology
Resistance to phages
Bacteria can develop resistance to phages, just as they do to antibiotics. Hence the shift toward multi-phage cocktails, or protocols combining phages and antibiotics synergistically.
Methodology
Heterogeneous evidence
The 2025 meta-analysis notes that trials remain poorly standardised (personalised vs fixed preparations), which complicates direct comparisons between studies.
Why this logic resonates with a naturopathic approach, and where the comparison ends
The underlying appeal of phage therapy, from a naturopathic perspective, lies in its logic of targeting: acting on a precise cause without disrupting the broader bacterial ecosystem, an approach that echoes a philosophy of caring for the terrain rather than broad-spectrum eradication.
Do not blur the two registers. Phage therapy is an experimental medical treatment, administered in a hospital setting under strict medical supervision, with laboratory selection of phage strains active against the pathogen identified in the patient (a phagogram test). It is not a naturopathic terrain-based practice (diet, microbiome, lifestyle), and it does not replace one. Placing it in the same register as conventional naturopathic approaches would create confusion between scientific popularisation of a medical research topic and terrain-based guidance.
Medical disclaimer
This article is for informational purposes only and does not constitute medical advice or a guarantee of treatment access.
Sources
- Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet, 2022;399(10325):629-655. Source
- Niazi SK. Bacteriophage Therapy: Discovery, Development, and FDA Approval Pathways. Pharmaceuticals, 2025;18(8):1115. Source
- Armata Pharmaceuticals / Lundquist Institute. Phase IIa diSArm: efficacy of bacteriophage therapy for Staphylococcus aureus bacteremia. IDWeek 2025. Source
- Auteurs multiples. Clinical application of customized and non-customized bacteriophage therapy in patients with refractory/resistant bacterial infections: a systematic review and meta-analysis. ScienceDirect, 2025. Source
- Auteurs multiples. Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches. J Clin Invest. 2025;135(5):e187996. Source
- Lapras B, Marchand C, Merienne C, Medina M, Kolenda C, Laurent F, Pirot F ; PHAGEinLYON study group. Rationalisation of the purification process for a phage active pharmaceutical ingredient. PubMed, 2024. PMID: 39111580. Source
- Ferry T, Le Bouar M, Briot T, et al. ; PHAGEinLYON Clinic Study Group. Access to phage therapy at Hospices Civils de Lyon in 2022: Implementation of the PHAGEinLYON Clinic programme. Int J Antimicrob Agents. 2024 Dec;64(6):107372. Source
- Ferry T, Kolenda C, Gustave CA, et al. Phage therapy in bone and joint infection: history, scientific basis, feasibility and perspectives in France. PubMed. PMID: 32108017. Source
- Hospices Civils de Lyon. Phagothérapie : les HCL autorisés à produire des phages thérapeutiques pour lutter contre l'antibiorésistance. Communiqué officiel, autorisation ANSM du 28 mai 2026. Source
- Eliava Phage Therapy Center. Institut Eliava de bactériophages, microbiologie et virologie. Tbilissi, Géorgie (fondé en 1923). Source
- Phage Therapy Unit, Institut Hirszfeld. Institut d'immunologie et de thérapie expérimentale, Académie polonaise des sciences. Wrocław (créé en 2005). Source
Sources last verified: June 2026.