Karolinska Institutet

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Saving the Antibiotic for Future Generations

World Health Organization (WHO) has classified the global issue of antibiotic resistance as a major threat to public health. In just Europe alone, approximately 30,000 deaths per year occur from infections with resistant bacteria and this figure is expected to have doubled in the next ten years.

In some countries, when there is risk of infection of such bacteria, the risk alone is causation enough to cancel a scheduled operation. Should we just give up then or is there light at the end of the tunnel? Well, first of all, we must change our behavior and not use antibiotics unnecessarily. Antibiotics should, in principle, be used to save lives and not for banal viral infections or colds. But if we want to save the antibiotic for future generations, new alternative treatments for infections with resistant bacteria must also be tested. These such trials are what is currently ongoing at the Center for Translational Microbiome Research, CTMR.

An alternative that seems promising is to compete the resistant bacteria in the intestinal flora with a “good microbiome” i.e., good intestinal flora. Currently ongoing in the laboratory is an experiment where resistant bacteria are supplied with a disturbed intestinal flora in test tubes and we then add “healthy intestinal flora” from a healthy donor. It is the same principle used in so-called fecal transplantation (FMT) where patients with diarrhea caused by certain antibiotics are cured with a healthy donor intestinal flora. We hope to be able to identify healthy donors whose intestinal flora can, in the future, help to compete with resistant bacteria in the intestinal flora of people who unknowingly carry. In this way, we can also reduce the risk of spreading resistant bacteria outside the body.

Another way to kill disease-causing resistant bacteria is phage therapy. Here, target-seeking viruses are used to eliminate the desired bacteria, usually with great precision. Phage therapy has long existed as a treatment option in Georgia and other post-Soviet states, but when the antibiotic entered the scene about 60 years ago the technique has not developed or advanced, as many thought antibiotics were the solution to all infectious problems. Now the researchers are beginning to realize that phage can be a good alternative when antibiotics cannot be used. Phage therapy also has the advantage that it does not interfere with the intestinal flora, which has proven to be a problem in antibiotic treatment, where even “good” bacteria are eliminated as well.

At our center, several trials are now underway. One of which we use test tubes containing good intestinal flora, then we add resistant bacteria and lastly the phages that kill them. Our results show that the phages do not disturb the intestinal flora at all and that the number of resistant bacteria decreases markedly in the test tube. The next step is to transfer this principle to humans. Today, there are occasional reports of successful treatment in patients where antibiotics did not work and where the patient’s life was rescued thanks to phages who did the job instead. A combination of phages therapy as well as supplying a dose of good intestinal flora could also be tested in some patients.

If we can prevent the spread of resistant bacteria by changing our behavior while developing new alternative treatments for infections with resistant bacteria then hope is not out. Then future generations can also use antibiotics when needed, i.e., to save lives.

Lars Engstrand is a doctor and professor at Karolinska Institute and leads the work at the Center for Translational Microbiome Research. He has been studying microorganisms in the gastrointestinal tract for over 30 years and is one of the pioneers in studying the role of the gut flora in health and disease.

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