Antibiotic resistance is linked to nearly 5 million deaths annually and could overtake cancer by 2050

The scale of the problem is measured in millions of lives. According to 2019 data, nearly five million deaths annually are linked to antibiotic resistance in one way or another, and more than one million deaths are directly caused by it. Unless the trend is reversed, Antibiotic resistance is expected to kill 10 million people annually by 2050, surpassing cancer. Even the current figure of one million is comparable to the number of people killed in traffic accidents each year or the total number of deaths caused by malaria and HIV. Economic losses amount to hundreds of billions of dollars.

Resistance is not a human invention. Most modern antibiotics are natural substances that have been around for millions of years, and resistance genes have always been present in nature: they have been found in Egyptian mummies and in permafrost. There are two mechanisms at work. The first involves chromosomal mutations, which are random errors in DNA that prevent the antibiotic from binding to its target. These mutations occur spontaneously. The drug only kills sensitive bacteria, leaving resistant bacteria in the open. The second involves resistance genes that allow bacteria to break down the antibiotic molecule using an enzyme or pump it out of the cell. These genes can move freely between different bacteria, including through plasmids – circular DNA molecules.

Why some infections can be treated with the same drug for decades depends on the combination of bacterial species and drug class. In the bacteria that cause tuberculosis, the main mechanism is target mutation; In other species, they are mobile genes and enzymes. Lyme disease represents a third condition: In the presence of an antibiotic, the bacteria become dormant, stop growing and forming protective layers, and then wake up with the same sensitivity once the drug is gone. No genetic changes occur. Gilyarov compares this mechanism to cancer treatment, where actively dividing cells die while dormant cells survive the treatment.

Agriculture is the main source of spread of resistance genes, and two separate issues are important here. In the middle of the last century, farmers noticed that small doses of antibiotics accelerated weight gain in pigs and poultry. This mechanism was never created, but the economic benefit was clear. This practice was later recognized as a problem and was banned in many countries. The second issue is the treatment of animals in intensive farming, where crowded conditions facilitate the spread of infections and parasites. Europe is trying to grow without huge amounts of drugs and without sacrificing profitability, which Gilyarov says is entirely possible. But this is not the case everywhere: agricultural use of antibiotics in China is enormous, while India faces the problem of drug manufacturing waste discharging into wastewater.

The result is global: resistance genes are now widespread even among normal bacteria in the human gut. This bacteria in itself is not dangerous. The danger arises when a person with a weakened immune system is hospitalized and the bacteria reach the lungs or wounds, causing an infection that is difficult to treat.

Gilyarov believes that concerns about antibiotics in meat are overblown: Regulatory standards prohibit pathogenic bacteria and drug residues above permissible levels, and animals must go through an antibiotic-free withdrawal period before slaughter. It is difficult to evaluate trace amounts and their impact on the gut microbiome. At the same time, he says that reducing meat consumption would make a real contribution to solving the problem: lower demand means less production, less use of medicines, and less entering the environment.

The second lever is the way hospitals operate. The introduction of antimicrobial stewardship rules combined with sanitation measures – proper sterilization, catheter care, infection prevention – can truly reduce resistance within an individual institution. Adherence to these practices varies even within a single health care system. Gilyarov was shocked by British statistics that showed this People living in economically deprived areas of England are 43% more likely to develop a drug-resistant infection than those living in affluent areas. The differences between countries are even more pronounced: the situation in Scandinavia is much better than in southern Europe, India, or Russia.

The effects of the epidemic and wars were mixed. On the one hand, overcrowding in hospitals, ventilators, and prophylactic prescriptions for antibiotics “just in case” have contributed to increased resistance. On the other hand, masks, protective suits and strict separation of patient flows had the opposite effect; Data from individual hospitals shows that stricter hygiene measures have had a positive impact. In the event of war, the picture becomes more local: a front-line hospital cannot maintain perfect sterility or wait for laboratory tests, while wounds are contaminated with soil, facilitating the development of infections caused by resistant bacteria. But this is an effect seen in specific institutions, not a global shift.

Individual misuse of antibiotics, including to treat viral respiratory infections, also increases the risk that treatment will one day fail. But Gilyarov describes resistance as a population-level problem rather than a personal problem: resistant bacteria do not “attach” a specific person as punishment for past mistakes. Stopping the cycle early is not a disaster either, the recent trend is instead towards shorter treatment durations.

The real consequences of unnecessary use of antibiotics relate to the microbiome. The human intestine contains about two kilograms of bacteria, and the antibiotic primarily eliminates beneficial anaerobic species, including bifidobacteria, whose numbers can be reduced hundreds or thousands of times. Diversity decreases, while the probability of colonization by Clostridium or pathogenic strains of Escherichia coli increases. The population recovers within several weeks after stopping the drug, but not always completely: in some cases, the balance does not return to its original state even after years. The effect is most pronounced in children under three, whose microbiome has not yet stabilized. Fiber helps him recover.

The current state of science makes a more precise answer difficult. Until recently, there were no technologies capable of tracking genetic changes in bacteria in real time within a patient taking antibiotics and then examining their condition a year later. Results also depend on the region, class of drug, and immune system of the individual.

Another problem is the almost complete halt in the development of new drugs. Historically, the productive period involved analyzing soil microorganisms, particularly Streptomycetes, which produced the lion’s share of known antibiotics: researchers grew the cultures, observed which organisms they killed and isolated the active ingredients. The most easily discovered discoveries have already been made. Bacteria are capable of producing hundreds of new molecules, but only in small quantities and only when they need to defend themselves against competitors. Their arsenal extends beyond chemicals, and also includes proteins and syringe-like devices that inject toxins into nearby cells. These systems could also eventually be used against pathogens.

The economy makes development unprofitable. Regulatory requirements have become so stringent that some antibiotics that made medical history would not be approved today due to their toxicity. It takes 10 to 15 years to bring a new drug to market and costs millions of dollars. However, antibiotics are cheap, treatment courses are short, and the number of patients eligible for any given molecule is small. If the drug is reserved as a last resort, the company will not be able to recover its investment. There is also vulnerability to off-brand drugs: unlike complex biotech products, an antibiotic is easy to imitate, and a drug that took decades and hundreds of millions of dollars to develop can be reproduced without a license. As a result, major companies have almost completely abandoned this field, and only a few remain, such as GlaxoSmithKline, Novartis, and Sanofi. The research is now led by startup companies, which test the molecule and sell it if it works or go bankrupt if it fails.

Gilyarov sees government incentives as the way forward. England applies a subscription model under which the health service pays for development regardless of future sales. The other option is to guarantee purchases at a fixed price even if the medication is never used. Such arrangements exist in developed countries but have not become a global standard. Against this background, academic science plays a larger role: some laboratories search for new molecules, while others determine how they work. Researchers are also increasingly returning to substances discovered in the 1970s as a starting point for entirely new classes of drugs.

Bacteriophages, often touted as an alternative to antibiotics, have been known for more than a century and have been extensively studied in the Soviet Union, especially in Georgia. However, no phage therapy has been formally approved or completed every stage of clinical trials yet. The reason is insufficient effectiveness. Phages are complex biological structures rather than small molecules: they degrade quickly in the bloodstream, struggle to reach deep tissue in a wound, and are difficult to dose predictably because they replicate within the body. It is also difficult to choose the right phages, as it is impossible to quickly determine which phages are needed for a particular infection, and a seriously ill patient does not have time to get tested. There are documented cases in which seriously ill patients have been saved, but they remain within the scope of experimental medicine. Phages also have big advantages: they are non-toxic to humans and have been attacking bacteria for billions of years, so resistance evolves differently. Some startups are already developing artificial intelligence tools that match phages to the genetic code of bacteria.

Meanwhile, another line of research seeks to restore the effectiveness of existing drugs. Bacteria produce beta-lactamase, which breaks down penicillin and related antibiotics, so doctors use combination therapies consisting of an antibiotic and an enzyme inhibitor, although enzymes develop resistance to inhibitors as well. A similar approach could inhibit the transporters that pump antibiotics out of the cell. Gilyarov’s laboratory studies the proteins responsible for fluoroquinolone resistance. A third approach is to make the bacteria themselves less dangerous by preventing the transfer of plasmids between them and suppressing their production of toxins and their ability to form biofilms.

In theory, old medications could also be returned. By changing a target to protect itself, the bacteria impairs the function of its own protein, which evolution has optimized for rapid growth. When the selection pressure is removed, the share of resistant bacteria in the population consequently decreases, and the drug may begin to work again. Complications are compensatory mutations: bacteria can sometimes restore the normal function of a protein while retaining its resistance, allowing this resistance to persist for a long time even when the antibiotic is not used.

Gilyarov’s overall view is cautiously optimistic: examples from individual hospitals show that resistance declines when antibiotic use is reduced, and with a clear target and adequate funding, it is possible to bring the problem under control. The obstacle here is that the world is preoccupied with other things: military conflicts, epidemics, and political instability. He compares the issue to climate change, where the global good is lost to short-term interests, and downplays the individual contribution with a simple rule: Don’t take antibiotics unnecessarily, and explain the same principle to those close to you.