Antibiotics part 2 a double-edged sword

Nov ,25 2016

In 1945, in his Nobel Prize winner’s speech, Sir Alexander Fleming had foreseen that microbes would develop resistance to penicillin if it is used unwisely. Unfortunately, as we know now, his words turned out to be true. But why do the microbes develop resistance? And how is it possible in the first place?

In nature, there is a constant fight among microbes for space and nutrients. During this fight, some microbes produce substances toxic to other microbes to take an advantage. However, confronted microbes can “armour” themselves in order to survive until the invading microbes develop a new antimicrobial compound. And when they do the cycle starts all over again, in other words, the natural selection is happening.

Unlike microbes, our bodies have not developed such a defensive mechanisms against bacteria. And when Fleming and other scientists discovered antibiotics, we thought we had found an ultimate weapon against the deadly bacteria. However antibiotics in their synthetic form have lost the ability to evolve as it occurs in nature. As long as there were new antibiotics discovered, the resistance was not considered a big problem. However, despite the huge diversity of bacteria, we have not discovered a new class of antibiotics since 1980s.

And antibiotics and antimicrobial are more widespread than many people might imagine, consequently, the vast majority of them is misused or wasted. For example, many people don’t finish their course of antibiotics. Since some bacteria are naturally stronger than others, these bacteria will survive and develop resistance to antibiotics and become even stronger and harder to kill. Antibacterial products are also hidden in soaps and other cleaning products in people’s bathrooms and kitchens. Antibacterial and antimicrobial agents were created to prevent the spread of infections in hospitals and they are good at their job. But in order to be efficient, the antimicrobial soaps require full 20 seconds of washing your hands. And when companies started selling these products, they left this piece of information out of their adverts. As a result, antimicrobial soaps are wasted and more microbes are developing resistances to these agents and may become more virulent than they were before.

Importantly, antibiotics are also widely used in agriculture to prevent and to cure diseases in the livestock. In addition, long-term administration of low antibiotic doses, also known as a subtherapeutic antibiotic use, is often used to improve growth and reproduction of animals. As a result, our reckless use of antibiotics and antimicrobial products has led to widespread problems with evolution of drug-resistant bacteria and spread of antibiotic resistance. It is a serious problem and according to the World Health Organization the antimicrobial resistance is a "serious threat that is no longer a prediction for the future, but it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country".

It seems that several simple measures could help to reduce the antibiotic resistance. The key is to spread awareness and knowledge among people. But there are still doctors prescribing antibiotics to patients with viral infections like flu or common cold, or vice versa patients are demanding antibiotics as a cure for every disease. But antibiotics do nothing against viruses. On a flip side though, Europe has banned the use of antibiotics to boost the growth of livestock. However this practice is common in other parts of the world.

And bacteria are fickle foes. Some species of bacteria can double their population every 20 minutes so in the presence of antibiotics the resistance can emerge pretty rapidly. But more importantly, bacteria can swap pieces of their genetic codes with other bacteria even from different species in a process called conjugation. As a result, beneficial mutations that often change the structures targeted by antibiotics can quickly spread within the bacterial world.

Consequently, in 2008, bacterium Klebsiella pneumoniae carrying a gene for New Delhi Metallo-beta-lactamase-1 (NDM-1) was detected in Sweden in a patient of Indian origin. NDM-1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics including carbapenem family, which are used to treat multi-drug resistant bacterial infections. NDM-1 has probably appeared in India where poor sanitation and broad antibiotic use helped the emergence and the spread of the NDM-1 gene. So far, NDM-1 has been found in E. coli and Klebsiella and it has been already found around the world including the United Kingdom, the United States, Canada, and Japan, most likely as a result of the international travel.

Meanwhile in Brazil, for the first time the scientists have detected E. coli harbouring an MCR-1 resistance gene against colistin, an important antibiotic, in humans. Colistin remains one of the last-resort antibiotics for treatment of multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa as well as Enterobacteria harbouring the NDM-1 gene. Interestingly, the Brazilian scientists were monitoring the occurrence of the MCR-1 gene and they found that colistin resistant E. coli was present in food-producing livestock since at least 2012. Importantly, Brazil is a major producer and exporter of poultry and commonly uses large quantities of antibiotics including colistin, to promote livestock growth. Prior to Brazil, the plasmid bearing the MCR-1 gene had been detected in E. coli and Klebsiella pneumoniae in Europe, Asia (China), North America, and South Africa. Surprisingly, the plasmid responsible for the colistin resistance is highly similar despite having been found in different species of bacteria, on different continents, and isolated under different clinical conditions suggesting that a single structure is responsible for the resistance.

The antibiotic resistance has enormous health and economic consequences. Patients fighting with infections that can’t be efficiently treated are spend longer time in hospitals and are in higher risks of life-threatening complications. Consequently, there is the economic impact of not being at school or work. And the future prospects are not very optimistic. According to a Review on Antimicrobial Resistance, the multi-drug resistant bacteria will kill every three seconds by 2050 unless we start acting now. So it is the highest time to take the action.