The risks of bacterial resistance

Indiscriminate or incorrect antibiotic use interferes with the microbiota; changes make bacterial infections more difficult to treat

Andreza Francisco Martins*

Bacterial resistance is a natural phenomenon, which can occur spontaneously. However, in recent decades, humanity has been faced with a significant increase in the rate of infections caused by multidrug-resistant bacteria, which have sometimes been labeled “Superbugs.”

The impact of this is seen daily in hospitals’ Intensive Care Units (ICUs), where more and more patients are affected by bacterial infections that are difficult to treat and often result in death. Thus, in 2016, the World Health Organization (WHO) classified the bacterial resistance phenomenon as a global health threat. At that time, it was estimated that the phenomenon could cause 10 million deaths per year worldwide in 2050.

What was not known when these projections were made is that there would be a pandemic, caused by a respiratory virus (SARS-CoV-2), that would greatly increase antibiotic use in both hospitals and communities, further worsening the scenario. But have you ever wondered: Why does this happen? How does bacterial resistance spread? Can we do anything to prevent this catastrophe?

The discovery of antibiotics was a major medical achievement that has already saved many lives. Prior to this discovery, a simple nail puncture to the foot could lead to a serious infection resulting in limb amputation or even the patient’s death. But the decision to use antibiotics comes with a price: the impact it has on the bacteria living in our body—the so-called normal microbiota.

The pandemic and antibiotic use

Even when used properly, antibiotics interfere with our microbiota. Abusive or inappropriate use (improper dose, stopping use before prescribed, incorrect administration time) interfere even more in this environment. What has occurred over the last two years is a substantial increase in antibiotic use due to the COVID-19 pandemic.

Insecurity, fear, and lack of knowledge led many people to use antibiotics for so-called “preventive treatment” or “early treatment.” However, what these people did was interfere with the normal microbiota, mainly in the gut.

Bacteria in the gut microbiota are the most affected by oral antibiotic use. The most sensitive will die and the most resistant will survive. Those deemed “the most resistant” will, through their own mechanisms, remain in the intestine. It is what we call “selection pressure.”

When the environment is favorable, they resume proliferating and may even “pass” resistance genes to other strains or species in the intestine. Due to the death of the previous generation’s ill-adapted bacteria, this population will contain more bacteria that show some form of antibiotic resistance.

So, in the future, when this individual has an infection, they may not respond to treatment. It is the old maxim for evolution: “The most adapted organisms will survive.” But does human antibiotic use alone impact bacterial resistance? How does the environment influence this process?

We know that resistance genes naturally occur in environmental microbiomes, independent of human action. However, do our current behaviors and activities contribute to the spread of resistance? In 2015, authors such as Van Boeckel and colleagues demonstrated a 36% increase in antimicrobial consumption in 71 different countries between 2000 and 2010, and 76% of this increase occurred in BRICS countries (Brazil, Russia, India, China, and South Africa). A curiosity is that, in these countries, meat consumption is growing due to the population’s greater purchasing power.

The large-scale animal production system generates large volumes of waste that may include significant concentrations of antibiotics, since the amount of antibiotics used in animal production is greater than that used in human medicine. Almost half of the antibiotics used in meat production in BRICS countries are for non-therapeutic purposes, such as growth promotion. This has been associated with increased isolates of multidrug-resistant microorganisms detected in chickens and pigs in recent years.

Livestock farming

The significance of how animal production systems contribute to the risk of spreading bacterial resistance in humans has been questioned, since only a few antibiotics used in agriculture are considered clinically important for human medicine. However, widespread use of antimicrobials (for example, quinolones, colistin, third and fourth generation cephalosporins) as growth promoters, prophylaxis, or livestock treatment highlights the role of animal production systems as reservoirs for resistance genes.

In livestock farming, antimicrobials are frequently added to feed or drinking water because it is impossible to treat each animal individually. Therefore, it is difficult to control the antibiotic dose that each animal receives. Thus, in livestock farming, antibiotic residues can aid in the selection of resistant bacteria and promote the exchange of resistance genes among normal microbiota and pathogenic bacteria.

As an example, we will highlight the spread of the plasmid-mediated mcr-1 gene. This gene causes polymyxin-resistance and has relevant implications for treating gram-negative bacteria, particularly carbapenemase producers (resistant to carbapenems).

Finally, the environment in which we live also plays a vital role in the spread of bacterial resistance. Hospital, industrial, agricultural, and livestock farming effluents release a large quantity of antibiotic residues into the environment, inducing mutations in the microorganisms living there so that they can survive the inhospitable environment. Although most of these environmental microorganisms may not be pathogenic, many have the potential to transfer resistance genes to other species, as well as elicit genetic recombination leading to the retention of these genes in opportunistic microorganisms.

Human beings’ increasingly close contact with urbanized and polluted areas increases the risk of spreading resistance determinants that are originally found in the environment.

Considering this situation, we need to improve diagnostic methods, monitor and regulate antimicrobial use, and establish public policies aimed at controlling the spread of bacterial resistance. In this way, we can prevent the looming post-antibiotic era.

*Andreza Francisco Martins is a professor at the Federal University of Rio Grande do Sul (UFRGS).

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