I am regularly asked why we don’t treat infections caused by multidrug resistant bacteria with bacteriophages. Last Friday, the same question made it to the best viewed talkshow on Dutch television (The World Turns On), and in about 10 minutes the global threat of antibiotic resistance was resolved. Here is how….
A short summary of the item (see here, about 10 minutes, in Dutch) with Antoinette Hertsenberg, a well-known TV personality with a background in communication and PR, the host and a by-sitting comedian:
“A recent study demonstrated that currently 700.000 and in the future 10 million people die each year because of antibiotic resistance. This implies that you can get a community-acquired urinary or respiratory tract infection not responding to any antibiotic, until death follows. Indeed, Dutch GPs see many patients that have become resistant. Yet, there is a solution, already 100 yrs old, neglected by the medical community, but available in Tbilisi (Georgia): bacteriophages, virus-like parcticles that specifically kill bacteria. A patient with a diabetic foot, toes scheduled for amputation, went to Tbilisi, was treated with phage therapy for 3 bacteria and the wound healed (look at minute 6.24 for how to apply the therapy: no gloves and nice rings). A family was told to say goodbye to father because of an untreatable infection. His GP ordered a phage in Tbilisi. As the urologist refused to insert the phage, homecare did, and 4 weeks later the patient was clean. Host: How is it possible that GPs and other physicians are wrong when they say we can’t do anything for you? Answer: Physicians just don’t know that you can treat patients with phages, and as it is not in protocols, they refuse to use is. Yet, phage therapy only attacks bad bugs and is cheap. Comedian: phages are probably even better than antibiotics for susceptible bacteria? All agree. Remaining research question: no phage yet identified to treat Lyme disease. Why is industry not interested? Answer: You can’t patent phages as they can be found in sewage. Final words: politicians must make sure that each country has a phage library!”
Where to begin with a response? The numbers referred to come form the O’Neill report, and its scientific value has been discussed here. In the Netherlands, the number of patients with untreatable infections seen by GPs can be counted on the fingers of one hand (even after multiple finger amputations), and that’s probably also close to the number of deaths attributable to antibiotic resistance in community-acquired infections. What was not discussed is the difference between topical treatment (with an ointment or fluids) and intravenous treatment. The efficacy of phages to lyse bacteria in a test tube is spectacular, but (un)fortunately a human being is more complex. Phages and their active enzymens are proteins that evoke an immunological host response when injected, and up till now all attempts to circumvene those unwanted effects have failed. Current use of phages is, therefore, for topical treatment only. Which implies, I have heard, that anyone can start selling an “ointment with phages”, as it is not considered a medicine and thus doesn’t require data on efficacy, safety, or proof that the product contains phages (if untrue, I will immediately withdraw this statement). Well-designed studies to compare these products with our standard of care are lacking and – in my own experience – producers are not interested in such trials. In pigs colonized with MRSA bacteriophage thearpy failed, see.
Micreos, a Dutch company, “develops the world’s first targeted antibacterial products, set to replace antibiotics. The company is viewed as global leader spearheading this exciting new field. With Micreos endolysin (the killing enzyme from the phage) technology, for the first time we can kill only the unwanted bacteria – including antibiotic resistant strains – while preserving the beneficial bacteria, essential for our health. Micreos’ Staphefekt SA.100 is an enzyme (endolysin), which kills only Staphylococcus aureus, including MRSA. It is suitable for daily maintenance therapy, for inflammatory skin conditions such as eczema, rosacea, psoriasis and inflammatory acne and has already had a life changing impact for thousands of people. ”
Interesting and impressive, but I couldn’t find any clinical study resulst supporting the thousands of life events.
Most experience is derived from in vitro or animal experiments with topical application of phages for Gram-positive infections, see these 2 reviews (1 & 2). Other facts: the global AMR crisis is driven by emergence of resistance among Gram-negatives causing infections that need systemic treatment. Therefore, even if topical phage therapy would offer benefits over conventional antibiotics in treating complex skin infections, diabetic feet or inflammatory skin conditions (which cannot be excluded without clinical studies) it would hardly inluence the course of the global AMR crisis. Nevertheless, the concept is highly interesting, needs further studies, but clinical use is not expected soon.
This Monday morning my thoughts are with all Dutch GPs answering their patients’ questions on why they have not yet been treated with bacteriophages. Suggested answer: “Relax, there are billions of phages in your gut that will protect you.”