“There will come a day when anyone can buy penicillin in stores. Then there will be the danger that an ignorant man can easily take an insufficient dose, and that by exposing his microbes to non-lethal amounts of the drug, he will make them resistant ”.
These prophetic words were uttered by Alexander Fleming on December 11, 1945, in his speech at the Nobel Prize award ceremony.
Currently, bacteria resistant to antibiotics are responsible for 700,000 deaths a year. The situation is not going to improve and it is estimated that by 2025 many of the usual antibiotics will be ineffective against the so-called “superbugs”. Globalization encourages new types of antimicrobial resistance to cross borders and spread effortlessly across continents. They are spreading at breakneck speed, and the growing increase in antibiotic resistance is already rampant, threatening to create a critical global health crisis.
It is essential to warn society about the global phenomenon of antibiotic resistance. Therefore, in a meeting held in May 2020, the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE) and the World Health Organization (WHO) decided that, Starting in 2020, Global Antimicrobial Awareness Week will be held every year from November 18 to 24. The motto will be ” Antimicrobials – Handle With Care .”
The main problem is that we are running out of alternatives with which to treat specific pathogens, particularly those that cause hospital-acquired infections, but have the potential to spread throughout the community. This indicates that antibiotic resistance could turn into a global catastrophe that, for the moment, shows no signs of abating.
Predictions suggest that by 2050 superbugs may cause 10 million deaths annually worldwide. In addition, health problems stemming from antibiotic resistance could cost the planet a trillion euros a year in healthcare, leading to a reduction of between 2% and 3.5% in gross domestic product.
WHO has listed multidrug-resistant pathogenic bacteria in three priority groups:
- Group 1: critical priority. It includes Acinetobacter baumannii, Pseudomonas aeruginosa, and some Enterobacteriaceae such as Klebsiella pneumonie, Escherichia coli, and several species of the Serratia and Proteus genera. All of them are resistant to carbapenems.
- Group 2 : high priority. It includes Enterococcus faecium (resistant to vancomycin), Staphylococcus aureus (resistant to methicillin and with intermediate sensitivity and resistance to vancomycin), Helicobacter pylori (resistant to clarithromycin), Campylobacter spp . (resistant to fluoroquinolones), Salmonella (resistant to fluoroquinolones) and Neisseria gonorrhoeae (resistant to cephalosporin and fluoroquinolones).
- Group 3: medium priority. It includes Streptococcus pneumoniae (not sensitive to penicillin), Haemophilus influenzae (resistant to ampicillin), and Shigella spp . (resistant to fluoroquinolones).
Resistances that have been in the making for decades
In the 1980s, some strains of Klebsiella pneumonie were found to be resistant to many beta-lactam antibiotics, a group to which penicillin belongs and which are among the most prescribed. The Klebsiella pneumonie strains were capable of producing enzymes called beta-lactamases that chemically inactivated beta-lactam antibiotics. This phenomenon heralded the first wave of antibiotic resistance observed in this bacterium.
It was very bad news and, far from improving, the issue got worse.
In order to treat beta-lactam-resistant infections, a group of antibiotics called carbapenems began to be used, which are a last-generation type of beta-lactams and which were very effective for a time.
Unfortunately, in 1996 it was observed that bacteria had developed another enzyme called carbapenemase that had the ability to hydrolyze and destroy carbapenemic antibiotics.
In 2009, the bacterium Klebsiella pneumonie showed a new mechanism of resistance to antibiotics, it was a metallo-beta-lactamase produced by the resistant bacteria found in a diabetic patient who had been administered multiple antibiotics after undergoing surgery in a hospital in New Delhi. In the same patient, a strain of Escherichia coli was also found that had the same type of resistance mechanism and that had been transmitted to him by Klebsiella pneumonie.
This exchange of resistance between different species greatly affects the future outlook.
Multi-resistance drugs forced the administration of a powerful antibiotic that is considered a last resort: colistin (polymyxin E). This drug alters the cell membrane of the bacteria and thus causes its death, but it must be used with caution because it produces certain toxicity in the human nervous system and kidneys.
In 2010, some strains of Klebsiella pneumonie were also found to be resistant to colistin. In 2015, the discovery of resistance to colistin mediated by plasmids carrying the mcr-1 gene, both in Escherichia coli and in Klebsiella pneumoniae isolated from humans and animals, caused acute global concern about the possibility of horizontal transfer of this gene between human and animal isolates.
Historically, colistin was first used in the 1950s intravenously. Colistin and polymyxin B have been used for decades in veterinary medicine for prophylactic and therapeutic purposes. Unfortunately the cross-resistance between colistin and polymyxin B is almost 100%.
In 2017, Nevada public health officials reported the case of a woman in Reno who died in September 2016 from an incurable infection caused by a strain of Klebsiella pneumoniae that was resistant to 26 different antibiotics. That is, all available in the United States. Neither was effective.
One billion dollars to break resistance
The problem has reached such magnitude that, a few months ago, more than 20 biopharmaceutical companies, with the support of the International Federation of Pharmaceutical Products Manufacturers and Associations (IFPMA), announced the launch of the Antimicrobial Resistance Action Fund (AMR) . It expects to invest more than $ 1 billion in the development of innovative antibacterial treatments. The goal is to develop 2 to 4 new antibiotics by 2030 for patients suffering from multidrug-resistant infections.
There are currently only 32 antibacterial treatments, in clinical development, targeting the WHO priority pathogens list. Of these, only 6 meet at least one of the innovation criteria defined by the WHO. We are falling behind and we may lose the race. Innovation can be the key. According to the latest WHO review, of the 252 antibacterial agents that were in preclinical development, more than a third were non-traditional products.
Considering the seriousness of the problem, a consensual approach to new strategies is urgent. For this reason, it is essential to communicate to the public the danger posed by these pathogens and to promote awareness in hospitals and research centers about the importance of approaching the scenario without waiting for the future. Also provide an open space for discussion of the various approaches and new findings.
Meanwhile, the general population must pitch in. We must apply prevention and control measures.
- Take antibiotics only when prescribed by a certified healthcare professional. Do not buy them if they have not been prescribed by a professional.
- Follow the instructions of the health workers regarding the use of antibiotics.
- Complete treatments.
- Do not reuse antibiotics or take leftovers from another treatment.
- Do not use them to stimulate the growth of animals and administer them only under veterinary supervision. Vaccinate animals to reduce the need for these drugs.
- Prevent infections with the pertinent hygienic-sanitary measures and handle food correctly and hygienically.
The WHO warns it and the proverb warns: “Prevention is better than cure”.
Raúl Rivas González, Professor of Microbiology, University of Salamanca
This article was originally published on The Conversation. Read the original.
