Bring on the era of post-modern antibiotics
08 Nov 2015
Magdalena Flak is a post-doctoral fellow in the Centre for Experimental Medicine & Rheumatology at the William Harvey Research Institute, Queen Mary University of London. Her research there studies the role of microbiota in the onset and progression of rheumatoid arthritis. Previously she spent five years at Brigham & Women’s Hospital, Harvard, in Boston, where she investigated the individual and combined contribution of the host and its microbiota to health and inflammatory bowel disease.
Not all microbes are bad. In fact, our bodies are the habitat of trillions of harmless bacteria, called commensal microbiota. Worryingly, a growing body of evidence links antibiotics overuse to disturbances in the communities of commensal microbiota. Such disturbances, in particular during childhood, are considered major contributors to the increased global incidence of asthma, obesity, type-2-diabetes, and chronic inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis.
In 1929, Alexander Fleming discovered the potent effects of penicillin, ringing in the “era of modern antibiotics.” Antibiotics went on to revolutionise the treatment of infectious diseases, surgery, and survival of immuno-compromised patients. However, the past decades have seen a lag in the discovery of new antibiotics, aggravating the threat of what is frequently referred to as a “post-antibiotic era,” when humans will once again succumb to ubiquitous microbial infections.
In order to prevent this scenario, we must attack the problem from different angles.
Better management of existing antibiotics
On the one hand, we have to restrict the use of currently available antibiotics.
This is by no means a call to stop treating patients who benefit from and depend on antibiotics treatment.
However, we must improve diagnosis. The faster doctors know which specific microbe is causing a disease, the better they can decide which is the most effective treatment.
We must reduce or stop the use of antibiotics in agriculture. Current antibiotics kill not only pathogens, but also commensal microbiota. Thus, reducing antibiotics-overuse and protecting our microbiota will decrease both, the risk of AMR and susceptibility to infections.
We must share and distribute information on the emergence and treatment successes (and failures!) of drug-resistant diseases more rapidly and comprehensively. The incredible pace of advances in computational technology must be used to enable doctors anywhere in the world to access information that may help them to identify diseases perhaps not previously encountered, to make informed decisions on containment strategies, and to be updated on novel treatment options.
More research & development of new antibiotics
On the other hand, there is also great urgency to develop novel types of antimicrobial drugs. In order to efficiently overcome the current and future emergence of drug-resistant microbes, new drugs must fulfill a range of criteria, for example:
They must be highly specific. The ideal antimicrobial drug will be highly selective in killing the disease-causing pathogen, but sparing both host cells as well as commensal microbiota.
They must be multi-faceted. An optimal antimicrobial drug will efficiently kill pathogens to reduce further spread and damage. Furthermore, it will regulate the immune response, promote clearance of inactivated pathogens and damaged tissues, and promote resolution of inflammation and tissue repair.
They must be personalised. Pathogens in one patient may develop a different drug-resistance mechanism in another. Horizontal gene transfer, a common mechanism in bacteria to exchange resistant genes between species, also depends on each person’s macrobiotic make-up. The ideal antimicrobial drug, therefore, should be modular, like Lego, to outpace development of AMR in cases of recurrent cycles of infection.
They must be combinable. In many cases the severity of inflammation will call for additional treatment to reduce it. Moreover, antimicrobial-resistant infections arise in patients, who are immune-compromised and thus required to take other drugs. The ideal antimicrobial drug will therefore be suitable for combination therapy with other medications.
More interdisciplinary research
“The more complex the world becomes, the more difficult it is to complete something without the cooperation with others.” – A. Fleming
Development of superior antibiotics, which will rapidly pass medical regulatory approval, requires an interdisciplinary research effort:
Microbiologists and immunologists, or perhaps best “microbiome-ists”, i.e. experts in the research on human-microbiota interactions, to study the behavior of all parties involved:
- the pathogens and their resistance mechanisms to identify their “Achilles heel”;
- the commensal microbiota, to see how they are affected by infection and by antimicrobial treatment and to identify strategies to better protect them;
- the patients, to assess effects on their health from the pathogen, the altered microbiota composition, the immune response.
Bioengineers, to develop technologies to simplify broad scale screening of candidate drugs; to design new devices that allow studying effects of candidate drugs on bacteria and human cells; to generate faster processing pipelines for data and results; and finally, to develop better diagnostic tools which will accelerate diagnosis and increase accuracy, allowing for rapid administration of the most appropriate therapy.
Clinicians to identify AMR infections, report clinical symptoms and flag up shortcomings of current and novel therapies, to help continually optimise antimicrobial therapy.
Without doubt, we have much catching up to do in the race against AMR. Yet, the basic tools for innovation are here. Researchers across different disciplines are increasingly interacting, seeking out each others’ expertise, collaborations are being built and ideas fostered – I would like to think we are well on our way to steer away from the “post-antibiotic era” and towards an “era of post-modern antibiotics.”