Antibiotic Resistance: A Global Crisis
Antibiotics have not only saved countless lives but also played a crucial role in significant advancements in medicine and surgery. They have successfully prevented infections in patients undergoing chemotherapy, complex surgeries like heart operations, and those with chronic conditions such as diabetes and kidney disease.
Antibiotics have been instrumental in effectively treating bacterial infections, thus extending life expectancy. For instance, in 1920, the average life expectancy in the United States was 56.4 years; today, it is around 80 years. Antibiotics have had similar beneficial effects worldwide, particularly in developing countries where sanitation and hygiene are still inadequate. In these regions, antibiotics help reduce illness and death rates caused by food-borne and poverty-related infections.
However, we are on the brink of a crisis in the fight against infections with antibiotics. Currently, antibiotic resistance is responsible for approximately 700,000 deaths annually. It has made treating many infections, including pneumonia, tuberculosis, and gonorrhoea, more challenging. If we fail to curb the development of antibiotic resistance in bacteria, it is estimated that preventable diseases could cause 10 million deaths annually by 2050.
How Antibiotic Resistance Spreads: The Impact of Agriculture
In both developed and developing countries, antibiotics are widely used in livestock as growth supplements. In the United States, an estimated 80% of antibiotics sold are used in animals, primarily to promote growth and prevent infections. It is claimed that the use of antimicrobials in livestock improves overall health, yields, and product quality.
The transfer of resistant bacteria from farm animals to humans was first recorded over 35 years ago. High levels of antibiotic resistance were found in the gut flora of both farm animals and farmers. Recent molecular detection methods have shown that resistant bacteria in farm animals can reach consumers through meat products. This occurs in several ways: 1) the use of antibiotics in food-producing animals kills or suppresses non-resistant bacteria, allowing resistant bacteria to thrive; 2) these resistant bacteria can be transmitted to humans via the food supply; and 3) these bacteria can cause infections in humans that may have adverse health effects.
The agricultural use of antibiotics also affects the environmental microbiome. About 90% of the antibiotics given to animals are excreted in urine and faeces, which then spread through manure, groundwater, and surface waters.
Antibacterial products sold for hygienic or cleaning purposes can also contribute to this problem. They can limit the development of immunity to environmental antigens in both children and adults. Consequently, the versatility of the immune system can be compromised, potentially increasing disease and mortality rates due to infections that would normally not be pathogenic.
Causes of Antibiotic Resistance: Overuse
In the early 1940s, Sir Alexander Fleming issued the first warning about the overuse of antibiotics, stating that the public would demand them, leading to their misuse.
Overuse of antibiotics triggers the evolution of resistance. Epidemiological studies have shown a direct relationship between antibiotic consumption and the emergence and spread of resistant bacterial strains.
In bacteria, genes can be inherited from ancestors or acquired from other bacteria through mobile genetic elements like plasmids. This horizontal gene transfer (HGT) allows the transfer of antibiotic resistance among different bacterial species. Resistance can also arise spontaneously through mutations. Antibiotics eliminate non-resistant competitors, leaving resistant bacteria to reproduce through natural selection.
Despite warnings about overuse, antibiotics are still heavily prescribed worldwide. In many countries, antibiotic use is unregulated and antibiotics are sold over the counter. This lack of regulation makes antibiotics easily accessible and contributes to their overuse. The ability to purchase these products online has also made antibiotics accessible even in countries where their use is regulated.
The Threat of Antibiotic Resistance
The modern antibiotic era began in 1928 with Sir Alexander Fleming’s discovery of penicillin. Since then, antibiotics have revolutionized modern medicine and saved millions of lives. Antibiotics were first used to treat serious infections in the 1940s. Penicillin was successful in controlling bacterial infections among soldiers during World War II. However, shortly after, penicillin resistance became a significant clinical problem, overshadowing many advancements made in the previous decade. In response, new beta-lactam antibiotics were discovered, developed, and used, providing a sense of security. But soon, the first cases of methicillin-resistant Staphylococcus aureus (MRSA) were identified in the UK in 1962 and in the US in 1968.
Almost all antibiotics developed eventually encountered bacterial resistance. Vancomycin was introduced in 1972 for treating methicillin-resistant S. aureus and coagulase-negative staphylococci. It was believed that resistance to vancomycin would be difficult to develop, but cases of vancomycin resistance in coagulase-negative staphylococci were reported in 1979 and 1983. From the late 1960s to the early 1980s, the pharmaceutical industry developed many new antibiotics to address resistance problems, but research slowed down afterwards, and fewer new drugs were introduced. As a result, bacterial infections have once again become a threat in 2015, years after the first patients received antibiotic treatment.
Causes of Antibiotic Resistance: Misuse
Improperly prescribed antibiotics contribute to the emergence of resistant bacteria. Studies have shown that in 30% to 50% of cases, the treatment approach, antibiotic selection, or duration of antibiotic therapy is incorrect. Additionally, 30% to 60% of antibiotics prescribed in intensive care units are found to be unnecessary, inappropriate, or below the required level. Misused antibiotics provide questionable treatment and expose patients to potential complications of antibiotic therapy. Sub-lethal antibiotic concentrations can promote genetic changes, such as gene expression, horizontal gene transfer, and mutations, leading to the development of antibiotic resistance in bacteria. Changes in gene expression due to antibiotics can increase pathogenicity, while increased mutation and horizontal gene transfer enhance antibiotic resistance and its spread. Low antibiotic levels have been shown to contribute to subspecies diversity in organisms like Pseudomonas aeruginosa.
A study in the UK found that at least 20% of antibiotic prescriptions in primary care were inappropriate. In response to this threat, the UK government aimed to reduce inappropriate antibiotic prescribing by 50% by 2020.
The Golden Age of Antibiotics and the Current Crisis
The “golden age” of antibiotics, which began in the 1930s, lasted until the 1960s. Unfortunately, researchers could not maintain the pace of antibiotic discovery in the face of emerging resistant pathogens. As a result, antimicrobial resistance has now become a global threat to human, animal, and environmental health. One of the most critical aspects of this threat is the emergence and spread of highly resistant “superbugs.” Among Gram-positive pathogens, the global outbreak of resistant S. aureus and Enterococcus species poses the greatest threat. Gram-negative pathogens are particularly concerning because they develop resistance to all available antibiotic options, creating situations reminiscent of the pre-antibiotic era.
In light of all this, many public health organizations have described the rapid emergence of resistant bacteria as a “crisis” or “nightmare scenario” with potentially devastating consequences. The World Health Organization (WHO) has warned that the antibiotic resistance crisis is worsening. The Centers for Disease Control and Prevention (CDC) declared in 2013 that humanity is entering a “post-antibiotic era.”
Conclusion
The battle between humans and bacteria is proving to be a fierce one. Although the discovery of antibiotics seemed to give humans an upper hand against bacteria, their superior selection capabilities have brought them back as a significant threat. As a result, the throne is under siege, and winter is coming!
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References:
- Ventola, C. Lee. “The antibiotic resistance crisis: part 1: causes and threats.” Pharmacy and Therapeutics 40.4 (2015): 277.
- Aslam, Bilal, et al. “Antibiotic resistance: a rundown of a global crisis.” Infection and Drug Resistance 11 (2018): 1645.
- Davies, Sally C. “Reducing inappropriate prescribing of antibiotics in English primary care: evidence and outlook.” Journal of Antimicrobial Chemotherapy 73.4 (2018): 833–834.