El futuro de los antibioticos

Since the discovery of Penicillin by Alexander Fleming, antibiotics have revolutionised medicine and saved millions of life. But over the last twenty years the cost of this success over bacterial infections has arisen. The widespread emergence of antibiotic resistance poses a major public health problem, threatening to reverse the life saving impact of Fleming’s discovery. A flurry of recent newspaper articles and research papers have discussed the impact of antibiotic use on resistance and efforts to overcome the dearth of new treatment options.

The introduction of antibiotics to treat bacterial infections is one of the most successful developments in medicine. However, this breakthrough is now threatened by ever-increasing levels of antibiotic resistance. Antibiotic resistant strains exhibit a greater ability to survive doses of antibiotics that would be lethal to typical strains. This higher resistance reduces the effectiveness of an antibiotic, leading doctors to use alternative antibiotics, which can eventually lead to the evolution of strains resistant to multiple antibiotics. Strains of multidrug resistant Staphlycoccus aureus and TB are spreading around the world, requiring ever harsher and expensive treatment regimes and causing increasing number of deaths. In the EU these mutltidrug resistant bacteria cause around 25 000 deaths a year, with costs as a result of treatment and loss of productivity estimated to amount to around 1.5 billion Euros. Where does this leave our aforementioned medical breakthrough? How has this widespread resistance emerged, and what can we do to counteract it?

Though most of the antibiotics in use now have been chemically synthesised, they stem from naturally occurring molecules that evolved over millions of years, as different species of microorganisms fought to reign supreme in their local habitat. During this times microorganisms have evolved to both produce, and overcome, different antibiotic molecules. When humans began using these molecules to treat bacterial infections, we exposed a far greater number of bacteria to far higher levels of antibiotics than would occur naturally in the microbial world. The result has been evolution in ‘real time’. Antibiotics act as a selective pressure leading to the selection of resistant bacteria within an environment, eventually leading to the loss of any susceptible species. To find out more about the evolution and mechanisms of antibiotic resistance, watch this animation produced by the US Food and Drug Administration.
Antibiotics when first produced were hailed as a miracle cure, demanded by patients to treat all types of illnesses. This widespread, and often misguided, use of antibiotics in humans as well as animals is responsible for the speed at which antibiotic resistance has evolved. Antibiotics have been used mistakenly to treat viral infections, such as colds, when they are only effective against bacterial infections. Many studies have shown the dynamic relationship between the prescribing of antibiotics and levels of antibiotic resistance in populations, and this has led to initiatives at all levels promoting the responsible prescribing of antibiotics. But, as an article in the Telegraph newspaper states, many patients are still wrongly given antibiotics for coughs and colds. Studies into why this is still occurring suggest a number of reasons for this, including that many patients and doctors do not appreciate the risk of antibiotic resistance evolving from a single course of antibiotics – considering it a problem of the population not the individual. A new paper published in the British Medical Journal (BMJ) this week, and featured in the Telegraph newspaper highlights for the first time the impact that antibiotics have on the emergence of antibiotic resistance in individuals.

The research conducted at the University of Bristol, in collaboration with the University of Oxford, reviewed and analysed previously published data on the emergence of antibiotic resistance after patients were treated for urinary or respiratory bacterial infections. They found that patients who were prescribed antibiotics were more likely to contain bacteria resistant to antibiotics for a period of up to 12 months after they had finished their treatment. Patients that took multiple courses of antibiotics during the 12 month period had a higher chance of having resistant bacteria within them. The researchers believe that the residual effect of antibiotics in promoting resistant bacteria is the reason behind the high levels of antibiotic resistance found in the community.

The work shows that in the case of antibiotics, one more really does make a difference. The researchers hope that this work will help to promote stricter prescribing of antibiotics and prolong the lifespan of our antibiotics.

Why when antibiotic resistance has been emerging for decades is its threat only now considered so serious? The era of antibiotics began in the 1920s and 30s with the discovery of Penicillin by Alexander Fleming and Protosil by Gerhard Domagk. From these original two, there are now over 13 classes of antibiotics, some into their fifth generation, consisting of both chemically synthesised and natural compounds. In their heyday, 15–20 new antibiotics were released each decade, but in the last ten years only 6 new drugs have come on the market and, according to an article in the same edition of the BMJ, only two new drugs are under development. It is this massive drop-off in new drugs which has led to the increased concern around antibiotic resistance. The previous approach of treatment with ‘something new’, no longer works when new drugs aren’t appearing.

Why has the production of antibiotics dropped-off and what can we do to promote it? An analysis and article by Morel and Mossialos in the same edition of the BMJ discusses this topic. The pharmaceutical industry has been reluctant to invest in research into antibiotics for a number of reasons. This includes the restrictive use of new antibiotics, with doctors reserving them for the most serious cases and the curative nature of the drugs making them far less profitable than drugs that mitigate symptoms. Antibiotic resistance itself is a disincentive for industry as it threatens to shorten the lifespan of the new treatment preventing sufficient financial returns. The European Council and the US have recently set up committees and task forces to promote the research and development of new antibiotics setting the goal of developing 10 new antibacterial drugs by 2020 – a sprint given the time taken for new drugs to be developed. How to go about jump starting industry to reach this goal is the central focus of these articles.

Together these articles highlight the critical state that we are in, and how close we are to losing this evolutionary race with bacteria. We require a concerted effort at all levels from patients to the pharmaceutical industry to conserve what we have and produce what we lack, antibiotics.

References
Course of antibiotics ‘can leave a patient resistant to that drug for up to a year’ Telegraph Newspaper 19 May 2010

Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis (2010) Costelloe et al. BMJ 340:c2096

Tackling antibiotic resistance (2010) So et al. BMJ 340:2071

Stoking the antibiotic pipeline (2010) Morel and Mossialos. BMJ 340:c2115

Fuente: British Society for Immunology.