Phage therapy and antibiotics: what’s the trade off?

After a mild bout of food poisoning over the weekend, my thoughts naturally turned to phage therapy. No seriously, they did. Generally when someone falls ill due to a bacterial infection, they are administered an antibiotic to kill the pathogenic bacteria. Antibiotics are not specific to one type of bacteria. This is one of the reasons they are so versatile and highly prized. While I did not receive a course of antibiotics I began to wonder about the trade off between broad spectrum antibiotics and highly specific phage.

What I really want to discuss with you is the merits of phage therapy in follow-on from my latest post regarding the safety of phage therapy here. How does antibiotic use compare to phage therapy? I do not have the literature or expertise to compare these two methods in a holistic manner so I have chosen two examples that interest me: orally administered antibiotics (e.g. for throat infections) and topical application of antibacterial ointments (skin infections). I will discuss broad spectrum antibiotics and the effects of their use the health of our gut bacteria vs. phage, and the difference in effectiveness for treating skin infections. Here’s the guts of it.

In the case of a bacterial throat infection, a patient can be prescribed an oral antibiotic. When taken properly, the symptoms of the sore throat will usually clear up quickly as the infection is overcome. However, orally administered antibiotics affect the balance of digestive bacteria in our gut. The human gut hosts an ecosystem of both beautiful, beneficial bacteria and brazen, bad bacteria. When a broad spectrum antibiotic is administered orally, the bacteria in our gut are also affected as the antibiotic passes through the digestive system. Broad spectrum antibiotics are fantastic because they allow us to treat a multitude of bacterial infections. They are very useful, especially if we do not know exactly which bacterium is making us ill. For phages to be used in therapy, the type of bacterium causing disease must be known because phage are specific to very few bacterium. The downside to oral antibiotics is the lack of control over what bacteria we do and don’t kill. If bacteria that aid our digestion and contribute to our overall wellbeing are sensitive to the antibiotic, they can be replaced by bad bacteria that have higher tolerance or are resistant to the antibiotic used and affect our overall wellbeing.

A very significant advantage of antibiotics over phage therapy is that antibiotics can be manufactured with very long shelf lives. From personal experience in the Phage Hunt labs, I have come to learn that phage are difficult to isolate and their storage is far more complex than I first imagined. Phage are ‘living’ things while antibiotics are chemical secretions that can be stored in capsules at room temperature. They do not always require refrigeration and they keep for long periods of time before losing quality e.g. months to years. It has been proposed that frequent phage use could lead to an antibody-neutralising response so with increased use, phage therapy will lose effectiveness as our immune system learns to recognise the phage. However, antibiotics can also lose effectiveness over time, particularly if they are misused. The danger of misuse is that it can also lead to antibiotic-resistant strains or ‘Superbugs’. Even ‘minor’ infections (e.g. a bladder infection), turned antibiotic-resistant can become lethal if our bodies’ cannot defend against them.

In the case of skin infections, phage therapy has been reported to be more efficient than antibiotics in some cases such as for ulcers treated in the USA. Perhaps this is because of phages’ size and the fact that they move by diffusion. I wonder if this allows them to penetrate deeper into infected wounds than topical antibiotic creams or sprays. It is worth noting that this study was not recent and lacked proper control and placebo treatments. In my research, I have found few recent studies on phage therapy. I expect this is because of the lack of research in this field  as phage were discovered 90 years ago after which, World War II and antibiotics stole the limelight.

Despite the lack of rigour in published studies and the abundance of research conducted on developing antibiotics, I still believe phage therapy has a lot of merit and should be investigated. As Sophie P posted; we are reaching peak-antibiotics. We are running out of antibiotic weaponry… and these have undesirable side effects (imbalance in gut flora). There have been no new classes of antibiotics discovered since the 1990’s and since then, we have discovered unexpected, infectious diseases that we cannot combat with our current antibiotic arsenal. If we cannot find new antibiotics to treat common and resistant bacterial infections, we need a new method of defence. Phage therapy has many challenges, scientific and ethical, but this should not deter us from new knowledge and discovery. We should remember that according to NASA’s log of space launches, 60% of launches failed to achieve their mission objectives. Even with this high failure rate, space launches still go ahead because we learn from our mistakes and we know there is more to learn. The same belief should apply here on Earth because there is so much to learn in the silent world of viruses. Who knows, what answers to phage therapy might just be awaiting discovery. We won’t know until we try.

Sources:

Bacteriophage therapy: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/

Phage treatment in humans: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278644/

Different approaches for using bacteriophages: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956485/

Antibiotics: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095020/ and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095020/

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