When thinking about obstacles to a broad use of phage therapy, regulatory hurdles, storing issues or efficacy concerns may come first into one’s mind. Yet, another major barrier is often forgotten: the lack of knowledge or disinterest of the people who are at the end of the phage therapy chain—physicians themselves.

In this issue of Capsid & Tail, I explore what physicians’ (mis)conceptions about phages are, and how we could improve awareness of phage therapy in the medical community. To help achieve this, I got input from two French physicians who recently used phages to treat their most desperate patients, Dr. Alexandre Bleibtreu (Assistance-Publique des Hôpitaux de Paris) and Prof. Tristan Ferry (Hospices Civils de Lyon).

Compassionate phage treatment of a multiresistant knee joint infection at the Hospices Civils de Lyon Hospital (France) - Taken from “Bacteria Killers, the Story of Phage Therapy”, directed by Jean Crépu, ARTE, 2019. © LADYBIRDS FILMS

Phage therapy and the medical community

Analysis of the phage therapy requests to the Queen Astrid Military Hospital (Brussels, Belgium), the largest center for phage therapy in Western Europe, revealed that phage therapy was sought three times more often by the patients themselves than by physicians.

The recent coverage of phage therapy by popular media may certainly have fueled the interest in this new therapeutic alternative. However, physicians, who have to decide whether to initiate a treatment by phages, are often ill-informed about this therapeutic possibility.

Lack of information during medical studies may be one major cause of the general ignorance of the medical community towards phages. In France, phages are for example not even mentioned once in the infectious disease textbook serving as the reference text for medical students nationwide.

Physicians then come to know phages by chance or during additional scientific training (e.g. Master of Science or PhD). This is how Dr. Bleibtreu first came in contact with phages: some isolates of the E. coli collection he was testing during his master’s studies showed atypical growth behavior, which turned out to be caused by phages. “It was surprising, but very far from therapeutics learned during my medical studies and fellowship”, Dr. Bleibtreu explains. “As a result, phages stayed in my mind but as an inaccessible possibility”.

Extensive exposure to science is limited to physicians engaged in academic careers, so this remains a limited way to raise awareness of phages among physicians.

What can be done to improve physicians’ awareness of phage therapy?

As Dr. Bleibtreu points out, “colleagues don’t know phages rather than are opposed to them”.

According to Prof. Ferry, combining cases of patients with homogeneous clinical situations (case series) and then performing clinical trials are paramount to increase awareness of phage therapy among physicians. Importantly, reports published in journals highly regarded within the medical community do a great job at bringing recognition to phage therapy, as did the recent article describing the use of engineered phages to treat a Mycobacterium abscessus infection, reported in Nature Medicine.

We must also underline the role played by pioneering doctors, who fought against odds to implement phage therapy. Tristan Ferry in France, Ard Struijs in the Netherlands, Ran Nir-Paz in Israel, Robert “Chip” Schooley in the US, to name but a few - they all demonstrated that use of phages was possible and could have a positive outcome. These early adopters of phages can then help their peers to introduce phages in their clinical practice, which can have a “snowball effect”.

Final words

Once again, for physicians and regulators alike, clinical trials are key to supporting a broader use of phages in the clinical setting. The current trend is encouraging, as cases accumulate and trials are being developed throughout the world. Only time will tell how fast phage therapy becomes common practice and enters medical textbooks.

Further information

• A recent reporting about phage therapy by ARTE, a French/German public broadcast service.