Antibiotic-resistant bacteria are specific strains of bacterial species that have developed resistance from the effects of antibacterial agents due to continued exposure. Take note that antibiotic resistance is a subset of antimicrobial resistance.
Nonetheless, the rise of several bacterial strains impervious to antibiotic therapies and the ongoing prevalence of antimicrobial resistance have now become a global public health concern. Infections from resistant microbes are hard to treat because they either require the development of new antimicrobial agents or administration of existing ones at higher doses.
General Cause of Antibiotic Resistance: Understanding Antibiotic-Resistant Bacteria
Evolution is at the center of antibiotic resistance. The emergence of antibiotic-resistant bacteria demonstrates the evolutionary processes that take place during antimicrobial exposure. Continued exposure to antibiotic essentially allows a specific bacterium to adapt and eventually evolve to the point in which it is no longer harmed by the antibacterial compound.
To be more specific, through the process of natural selection and evolutionary pressure, antimicrobial therapy may select for bacterial strains with enhanced capacity to survive the particular type of antibiotic in use. Under the right conditions, these resistant strains could propagate within the host or spread to the outside environment, such as in the case of hospital-acquired infections.
Different bacteria have different evolutionary mechanisms by which they develop resistance to antimicrobial agents. Some species may produce new resistant strains under low doses or concentrations of antibiotics. Other species may produce resistant strains under high concentrations while others response to high albeit abrupt concentrations.
Of course, it is also important to mention that resistance can occur naturally. Some bacterial strains have developed antibiotic resistance as a defense mechanism while in their natural habitats. Penicillin-resistant bacteria existed before the discovery and utilization of penicillin treatment. There are also other bacterial species with preexistent resistance to streptomycin.
Specific Factors Leading to the Emergence of Antibiotic-Resistant Bacteria
There are specific causes of antibiotic resistance, particularly factors that contribute to the emergence and propagation of antibiotic-resistant bacteria.
1. Misuse and Abuse of Medications
Remember that resistance can occur naturally, and some resistant bacteria strains predate the use of antibiotics in both healthcare and commercial or industrial settings. However, the widespread consumption of these antibiotics since the 1950s due to their clinical significance has promoted the emergence of more resistant bacteria.
The decrease in production costs and uncontrolled sales have increased the consumption of antibiotics. Prior to the recommendations from the World Health Organization and strict regulations from government agencies in different countries, antibiotics can be obtained without a prescription and a proper dosage guideline, thus enabling the misuse and abuse of these medicines by the local population.
Forms of misuse and abuse include self-medication, prescription by physicians without proper dosage and consideration of patient history, failure to complete the entire course of the therapy, and inappropriate treatment due to an incorrect diagnosis. The ICU Book by Paul L. Marino noted that the first rule of antibiotics is to try not to use them, and the second rule is to try not to use too many of them.
2. Use of Antibiotics in Agriculture and Livestock
A large body of studies has established the use of antibiotics in agriculture and livestock as a contributing factor to the emergence and propagation of resistant bacteria. The WHO specifically noted that the use of antimicrobial agents is prevalent in a production-intensive setting. In addition, in some countries, the total amount of antibiotics used in animals is four times greater than the amount used in humans.
Most countries also use antibiotics not to treat diseases in animals but to promote growth and prevention of diseases. Of course, researchers Quizhi Chang et al. noted that there are no data conclusively showing the magnitude of the threat from this practice. However, they identified three potential mechanisms by which the use of antibiotics in agriculture and livestock could affect the human population.
These mechanisms include direct infection with antibiotic-resistant bacteria from an animal source, breaches in the species barrier followed by sustained transmission in humans of resistant strains arising in livestock, and transfer of genes that confer bacteria with resistance from agriculture to human pathogens.
3. Antibacterial Agents in Consumer Products
Aside from use in a clinical or healthcare setting, antibacterial agents remain in key ingredients in a number of consumer products ranging from personal hygiene items such as skin care products to cleaning and home maintenance products such as laundry detergents, dishwashing soaps, and disinfectant sprays, among others.
The U.S. Food and Drug Administration banned 19 antibacterial additives such as triclosan and triclocarban commonly used in antimicrobial soaps and other personal hygiene products. Aside from the fact that these ingredients do not demonstrate necessity and long-term safety, they increase the risk of promoting bacterial resistance.
A study by Corey Westfall et al. revealed that triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo. For example, E. coli strains exposed to common antibiotics and triclosan were several thousands of times more likely to survive than E. coli strains exposed to the same antibiotics without triclosan. Furthermore, triclosan protects the Methicillin-resistant Staphylococcus aureus or MRSA strain from the last-resort medication called vancomycin.
4. Wastes From Pharmaceutical Companies
The magazine New Scientist published an article exploring how waste products from the operations of pharmaceutical companies in India are driving the rise of antibiotic resistance in the local population. It explained that these companies are dumping wastewater containing high concentrations of antibiotics in lakes and streams, thus possibly becoming breeding grounds for antibiotic-resistant bacteria.
A report by the Changing Markets Foundation and investigative agency Ecostorm revealed that 16 of the 35 manufacturing sites in India were harboring bacteria resistant to antibiotics. In addition, from the 16 sites, four sites were harboring bacteria resistant to the three major classes of antibiotics. The report also noted that China is also home to pharmaceutical companies with questionable wastewater management.
Researchers D. G. J. Larsson and J. Fick recommended the need for transparency in the production chain of pharmaceutical products, as well as changes in local and international regulations. Consumers should also be able to make informed decisions by providing readily available information regarding the origin of drugs and the environmental impacts of their production.
5. Antibiotic-Resistant Infections from Hospitals
Hospitals and other healthcare facilities are home to transmittable diseases. Researchers have investigated the different facets of hospital-acquired infections or HAIs. Some studies have focused on specific types of HAIs that are resistant to conventional antimicrobial treatments, including antibiotic-resistant, hospital-acquired bacterial infections.
A historical review of prior studies by A. Revelas revealed that bacterial infections are common in most HAI incidents. Gram-positive bacteria were the most common cause of HAIs from 1940 to 1950. During the late 1980s to early 1990s, HAIs caused by gram-negative bacteria emerged. Incidents of hospital-acquired bacterial infections have become more disconcerting due to the emergence of antibiotic-resistance bacteria during the 1990s.
In an article published online by the Center for Disease Control and Prevention, R. A. Weinstein explained the rise of resistant bacteria in the healthcare setting stems from failures of hospital hygiene or poor practices in maintaining a sterile environment, selective pressures created by overuse of antibiotics, and mobile genetic elements that can encode bacterial resistance mechanisms.
FURTHER READINGS AND REFERENCES
- Bomboy, A. and Barnéoud, L. 2019, May 22. “How Antibiotic Resistance is Driven by Pharmaceutical Pollution.” New Scientist. Available online
- Chang, Q., Wang, W., Regev-Yochay, G., Lipsitch, M., and Hanage, W. P. 2014. “Antibiotics in Agriculture and the Risk to Human Health: How Worried Should We Be?” Evolutionary Applications. 8(3): 240-247. DOI: 10.1111/eva.12185
- Changing Markets Foundation and Ecostorm. 2016. Superbugs in the Supply Chain: How Pollution from Antibiotics Factories in India and China is Fueling the Global Rise of Drug-Resistant Infections. Utrecht, The Netherlands: Changing Markets Foundation. Available via PDF
- Larsson, D. G. J. and Fick, J. 2009. “Transparency Throughout the Production Chain—A Way to Reduce Pollution from the Manufacturing of Pharmaceuticals?” Regulatory Toxicology and Pharmacology. 53(3): 161-163. DOI: 10.1016/j.yrtph.2009.01.008
- Marino, P. L. 2007. “Antimicrobial Therapy.” The ICU Book. Hagerstown, MD: Lippincott Williams & Wilkins. ISBN: 978-0-7817-4802-5
- Revelas, A. 2012. “Healthcare-Associated Infections: A Public Health Problem.” Nigerian Medical Journal. 53(2): 59-64. DOI: 10.4103/0300-1652.103543
- U.S. Food and Drug Administration. 2016, September 2. “FDA Issues Final Rule on Safety and Effectiveness of Antibacterial Soaps.” FDA Newsroom. U.S. Food and Drug Administration. Available online
- Weinstein, R. A. 2001. “Controlling Antimicrobial Resistance in Hospitals: Infection Control and Use of Antibiotics.” Emerging Infections Disease. 7(2): 188-192. PMID: 11294703
- Westfall, C., Flores-Mireles, A. L., Robinson, J. I., Lynch, A. J. L., Hultgren, S., Henderson, J. P., and Levin, P. A. 2019. “The Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In Vivo.” Antimicrobial Agents and Chemotherapy. 63(5). DOI: 10.1128/AAC.02312-18
- World Health Organization. 2017. “Antimicrobial Resistance in the Food Chain.” Food Safety. World Health Organization. Available online