Has COVID-19 Exacerbated the Surge of Antimicrobial Resistance?

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Author: Nazrin Rustamzade

Antibiotics, have revolutionized medicine and empowered humankind to survive the deadliest of infections. Ever since the commercialization of penicillin, antibiotics have become an inherent component of a wide range of routine medical procedures as well as, but not limited to cancer treatments and organ transplants. Antibiotics have played a significant role in decreasing morbidity and mortality levels caused by food – borne infections in poverty – stricken developing countries, where sanitation remains poor . However , the efficacy of antibiotics is substantially compromised and weakened by the bacteria’s ability to withstand exposure to antibiotic drugs . Bacteria evolve and adapt to their environments , eventually passing their mutations onto other types of bacteria through DNA. Anti microbial resistance (AMR) has risen to dangerously high levels all around the world , making common infections harder to treat. According to the United Nations, by 2050, antibiotic – resistant diseases could bring about 10 million deaths annually.1 Today, the all – consuming era of the COVID – 19 pandemic has temporarily replaced AMR in its bid for the world’s most pressing global threat. Unfortunately, this has allowed it to propagate behind closed doors and rise to previously unthought – of heights . Thus, it becomes critical to examine whether or not COVID – 19 has exacerbated the spread of antimicrobial resistance.

 

The coronavirus pandemic and antimicrobial resistance are extensively intertwined health emergencies that provide the public health sector an opportunity for mutual learning. Epidemiological studies have demonstrated a direct relationship between misuse and overuse of antibiotics in animals and humans and the vast dispersion of resistant bacteria. The acquisition of extraneous genetic elements is responsible for the rapid development and horizontal spread of resistance among bacteria. The spread of resistance is achieved through the expression of efflux pumps or drug – inactivating enzymes which together contribute to bacteria’s natural defense mechanisms against environmental toxicants.2 The use of antibiotics is largely unregulated, amounting to multiple antibiotic treatments being prescribed per person annually. Ironically, easy access to antibiotics , their efficacy capabilities, as well as their abundance and relative cheapness have immensely contributed to the overconsumption . In the United States alone, approximately 2.8 million people annually become infected with bacteria that are resistant to antibiotics with at least 35,000 dying as a result. Moreover, antibiotics are widely used as growth supplements in livestock. Approximately, 80% of antibiotics that are sold in the United States are used to promote growth and large – yields as well as prevent animals from contracting infections. However, these continuous antibiotic treatments of the livestock and the farmlands are oftentimes unnecessary and simply prophylactic. They create a favorable environment for resistant bacteria to proliferate within the animals as well as the agricultural produce and eventually end up in the human intestinal flora through the food supply chain. Up to 90% of antibiotics that are used within the agricultural sector are excreted in urine and stool as well as scattered through fertilizer and surface runoff, ultimately altering the ecology and increasing the proportion of resistant bacteria in the environment.3 When evaluating the growth of antibiotic resistance through the prism of coronavirus, it becomes important to understand that antibiotic drugs are ineffective at treating viruses. The pandemic has undoubtedly brought about medical uncertainty that has been continuously amplified by urgency. In the absence of correctly designated treatments, doctors in the hope of being overly cautious, have been falsely prescribing a wide range of antibiotics to COVID – 19 positive patients . It is crucial to remember that the prescription of antibiotics is only appropriate with patients who are experiencing severe cases of COVID – 19 and those at an increased risk of death due to high susceptibility to bacterial co – infections. Incorrectly prescribed antibiotics to those with mild forms of COVID – 19 have questionable therapeutic benefits, potentially exposing patients to secondary infections , caused by drug – resistant pathogens like Methicillin – Resistant Staphylococcus Aureus (MRSA) . The issue is further exacerbated by the fact that SARS – CoV – 2 often presents itself through symptoms that are associated with bacterial infections, making it difficult for physicians to draw a distinction. Michigan was one of the states that w ere hit hard during the onset of the pandemic. According to Valerie Vaughn, MD, a hospitalist at the University of Michigan’s academic medical center and the lead author on the Michigan study , the shortage of tests and delays in receiving test results in March 2020 and the fact that COVID – 19 positive patients frequently displayed bacterial pneumonia – like symptoms contributed to the surge of antibiotic use. The misuse of antibiotics was also reflected in the fact that physicians , in the face of ambivalence, started to prescribe broad – spectrum drugs , that lack the specificity of narrow – spectrum antibiotics and increase the probability of spreading resistance across multiple bacterial species. 56.6% of COVID – 19 patients received antibiotic treatment and the rate of prescribing antibiotics ranged from 27% to 84% across the state.4 Moreover, the misguided use of antibiotics is attributed to the rapid development of telemedicine: doctors are unable to perform auscultations and laboratory examinations, making antibiotic prescription guidelines more difficult to follow . Paradoxically , telemedicine previously allowed for the development of antimicrobial stewardship to monitor antibiotic prescription, however , the pandemic greatly halted the efforts. Today, the heightened need to be precautious and the preemptive assumption that every COVID – 19 patient is a potential carrier of bacterial infections contribute to the over – prescription of antibiotics during online consultations greatly outweighs that of in – person visits.

The rampant pandemic has created unprecedented challenges to the functionality of the healthcare system. COVID-19 treatments have substantially disrupted hospitals’ day-to-day operations ranging from overcrowded facilities ; low healthcare workers to patient ratios ; and medical equipment and PPE shortages to longer hospital stays ; disrupted supply chains ; and catastrophic financial losses. The healthcare setting, particularly intensive care units (ICU) , are considered to be the ultimate hotbeds of AMR . Even though routine medical procedures and surgeries, which usually account for hospital – acquired antimicrobial resistance , have been largely canceled, as coronavirus hospitalizations surge and ICUs reach their full capacities, the transmission of resistant bacteria between C OVID – 19 patients becomes inevitable. This surge of antibiotic resistance is tied to the prevalence of MRSA infections. Staphylococcus A ureus’ unique ability to quickly respond and become resistant to most clinically available classes of antibiotics by mutating through the acquisition of horizontally transferred resistance determinants has resulted in the fact that MRSA has become an endemic in hospitals worldwide. Ac cording to the Centers for Disease Control and Prevention (CDC), approximately 5% of patient s in U.S. hospitals carry MRSA in either their nasal cavity or their skin. MRSA bacteria can survive on a variety of surfaces for extended periods of time. Thus, whether it is through direct or indirect contact, MRSA transmission becomes possible through numerous entry points in crowded hospital settings . This is especially apparent at a time of a pervasive health crisis that has necessitated sessional use of PPE and made it more difficult for healthcare workers to abide by the Infection Prevention and Control (IPC) precautions.5 As stated by Dr. Chitra Punjabi, an infectious disease specialist, in the recent Infection Control and Hospital Epidemiology report, hospitalized COVID – 19 patients that are admitted with severe pneumonia are almost immediately prescribed anti–methicillin-resistant Staphylococcus aureus (anti-MRSA) agents , such as vancomycin to eliminate the threat of MRSA. Additionally, Dr. Punjabi concluded that as a result of the cohort study that was conducted across all campuses of the Montefiore Medical Center in New York, 904 (21.4%) out of 4,221 adult patients received vancomycin within 48 hours of admission. Early in the course of admission, MRSA was not commonly identified even in severely ill patients. However, the prevalence increased with a prolonged hospital stay, suggesting t hat the co – infections and complications were hospital – acquired.6 When diagnosing co – infections and assigning treatments to patients, critical emphasis needs to be placed on isolation measures to lower the risk of infection transmission between patients and healthcare workers. Unfortunately, the pandemic has dramatically diminished the number of available hospital beds as well as the hospitals’ capability to isolate patients. Furthermore, COVID – 19 has greatly undermined the successes of antimicrobial stewardship efforts. Traditionally, antimicrobial stewardship programs have been implemented across the healthcare system to improve patient outcomes and control the prescription of antibiotics. Ideally, these programs could have been remodeled and utilized in pandemic response efforts by providing hospitals the stewardship expertise to assess compliance with newly created guidelines, incorporate experimental treatments, and ensure the appropriate use of therapies. However, pandemic efforts and shifting priorities have resulted in the fact that preventative and continuing measures against AMR have been largely neglected. There is a growing concern that the pandemic’s strain on the overwhelmed healthcare system may disrupt the antibiotic stewardship programs that were designed to help the hospitals minimize the risk of AMR in the first place. 

COVID19 has exponentially altered the dynamic of our lives, introducing an array of health and safety measurements that have now embedded themselves into each one of our daytoday ventures. Unquestionably, the virus brought to light the significance of cleanliness and hygiene, leading to an inescapable rise in the use of disinfectants and sanitizing agents, consequently heightening concerns over the risks of overexposure and emergence of crossresistance in bacteria. Disinfection is a systemic and efficient way of killing pathogenic microorganisms. Nonetheless, there are no universal guidelines or monitoring mechanisms regarding the largescale application of disinfecting agents to control the spread of infectious diseases.7 The activity of disinfecting agents is reflected in the quantification of the minimum concentration that is required to inhibit the growth of target organisms (MIC). Increased surface cleaning and the growing concentration of disinfectants that are being used outdoors, in healthcare environments, and inhome settings have raised concerns over the changes in the MIC and the consequential development of bacteria’s tolerance towards disinfectants, namely biocides. Biocidal agents are widely associated with the food production chain, as they are regularly used to clean the areas and equipment associated with livestock and produce. Today, the application of biocides has shifted towards indiscriminate sterilization to combat the spread of COVID19. Unfortunately, because biocides do not possess high levels of target specificity and are, instead, characterized by their lack of selectivity, they only facilitate the emergence of crossresistant bacteria during low levels of exposure. Alternative storebought cleaning products follow a pattern of bacterial behavior similar to that of biocides, as they contain genotoxic agents that can damage or alter the DNA. Bacteria, then, become resistant as a result of the DNA mutations brought about by exposure to chemicals founds in these sanitizers. The more frequent the genotoxic events occur, the higher the probability of bacteria obtaining survival advantage. Moreover, the surge in the presence of antibioticresistant bacteria is tightly knit to the rapid spread of misinformation about COVID19, particularly the prevalence of the urban myth that the best hygiene practices involve the use of antibacterial soaps. The idestems from the misconception that additives found in antibacterial soaps, particularly a chemical compound called triclosan, are better at stopping the bacteria on your skin from replicating than a regular soap bar would. However, the ingredients found in antibacterial soaps generally do not affect viruses, thus the tempting label which markets the product as “effective against 99.9% of household germs” does not actually offer more protection against COVID19. According to the U.S. Food and Drug Administration (FDA), manufactures of antibacterial soaps, cannot provide any clinical evidence to support the claim that their products are superior to nonantibacterial soaps.8 In fact, there is mounting evidence to suggest that the perpetual use of antibacterial soaps may have a cumulative effect of exposure, causing adverse risks to human health by altering hormonal pathways as well as impacting the ecosystems. Additionally, the accumulation of triclosan perpetuates the risk of precipitating an increase in resistant bacteria. Triclosan-resistant bacteria have mutations in proteins called enoylacyl carrier protein reductases (ENRs), which are important for the biosynthesis of cell membranes. Hence, when the bacterial population on our skin is continuously exposed to products containing triclosan, especially through environmental accumulation, they develop a variety of mutations in the ENR, enabling them to survive and acquire resistance. The lack of conclusive evidence regarding the efficacy of antibacterial products points to the fact that if you are washing your hands with antibacterial soap, you are exposing yourself and the environment to high levels of chemicals without any measurable benefits.9 It is important to recognize that the largescale use of disinfectants not only contributes to the accumulation of AMR but also poses a threat to the health and safety of the ecosystem. The ecological consequences directly stem from the large quantities of chlorine being used as a form of disinfectant. As chlorine is distributed on the external surfaces, it becomes exposed to sunlight and readily undergoes continuous photochemical reactions, producing free radicals of chlorine. These free radicals can interact with methane gas emitted from the biodegradation of animal manure to reduce chloromethane, which is an extremely toxic and volatile organic molecule that breaks down very slowly and can be readily inhaled by humans and animals creating a variety of health hazards. Additionally, chlorinebased products that are discharged into the water systems produce high levels of persistent chlorinated organic and inorganic compounds that have longterm residual effects as well the ability to accumulate in both humans and aquatic animals. Lastly, some of these chlorinated hydrocarbons can reach plants, giving rise to phytotoxicity, leading to significant growth inhibition.10 The vulnerability of the flora and fauna further extends to the effects of miscellaneous and unsystematic use of disinfectants on microbial diversity. The stability and the functionality of the ecosystem rely extensively on microbial diversity which acts as a protective shield against the pathogens within the communities. The loss of microbial diversity is profoundly linked to an increase in resistant bacteria in the environment, indicating that microbial populations are burdened by antibioticresistant organisms. Furthermore, the use of antibacterial products heavily disrupts the human microbiome. As resistant bacteria survive and multiply in the gut, longlasting harmful changes to the human microbiota create a dysbiotic microbiome, effectively halting all of its vital functions such as nutrient supply, vitamin production, and protection from pathogens. Even though disinfection and adequate hygiene practices can help us prevent the spread of the virus from one person to the next, that does not imply the necessity to use antibacterial products and haphazard mass application of disinfectants that are presently only propelling the adverse selection pressure on the resistome and posing a significant threat to the environment.11

 

The research around the intricacies of antimicrobial resistance and the causal factors that are ascribed to this global health crisis is often limited to looking at the issue only from the perspective of humans overusing or misusing antibiotics. However, this unilateral approach pays little attention to the role of the agricultural sector, namely the interplay of antibiotic use in animal health and food production, and overlooks its impacts on human health. The high population density of animals and intensive food production practices result in different species sharing of commensal flora and pathogens, contributing to the rapid dissemination of infectious agents. The frequent occurrence of overcrowding, lack of hygiene, and poor living conditions for animals have contributed to the emergence and spread of Livestockassociated MethicillinResistant Staphylococcus aureus (LAMRSA) not only in animals but also in farm workers due to their proximity and frequent exposure to livestock. Oftentimes, animals are asymptomatic and whether or not they are a carrier can only be determined through MRSA screening, which, unfortunately, is not part of a routine surveillance program. As a result, misinformed farmers, engage in aggressive infection management treatments with antibiotic therapy to compensate for the high risk of outbreaks in these environments. In addition to that, farmers are often guilty of engaging in economically beneficial tactics such as using antibiotics as growth promoters in an effort to keep up with the demand.12 These unnecessary practices, as well as prophylactic strategies, contribute to the propagation of resistant bacteria in livestock, which eventually make their way into the food supply chain and onto the kitchen table, increasing the risk of consuming antibiotic residues in meat and poultry, providing a selection pressure in favor of antibioticresistant bacteria in the human microbiome. Despite an array of reasons why COVID19 has exacerbated the surge of antimicrobial resistance, it is essential to touch upon a possible impact that the current pandemic might have had on decreasing the risk of humans acquiring AMR from the agricultural domain, namely through a shift away from overconsumption of meat. One reason to believe that demand for meat may be decreasing is to consider the role that the media has played in accentuating the zoonotic nature of COVID19. The popularity of the term “zoonosis”the notion that infectious diseases could originate from animals-corresponds to the onset of the pandemic. According to recent estimates, six out of every ten known infectious diseases in humans arise from interactions with animals, while three out of every four emerging infections are predicted to become zoonotic. The enclosed conditions of factory farms area breeding ground for viral infections. Before the outbreak of SARSCoV2, there was a common sentiment of disassociation between animals and the food they produce, largely reflecting modern agricultural practices where consumers only interact with the end product giving little to no thought to the role that agriculture plays in accelerating the spread of infectious diseases and the accumulation of AMR in the environment.13 According to United Nations Food and Agriculture Organization (FAO), in July 2020, the per capita consumption of meat was set to drop to the lowest levels in nine years.14 Consumers are losing their confidence in the safety of their food, acknowledging the previously ignored risks of intensive animal husbandry and the spread of antimicrobial resistance through the food supply chain. The decline in the consumption of meat positively influences the transition away from an animalcentric food system, effectively decreasing the agricultural misuse and overuse of antibiotics, lowering human exposure to AMR. Moreover, because animal agriculture constitutes 18% of humancaused global greenhouse gas emissions, this retreat from meat consumption is bound to contribute to favorable environmental outcomes. Even though consumer preferences might be evolving, it is still crucial to remain wary of the fact that the human population is expected to grow by 50% by the year 2050, yielding a consequential increase in demand from the agricultural sector. Therefore, as stated by FAO, agricultural workers should uphold their status as “important frontline defenders” and acknowledge the vital role they play in halting the spread of AMR by adopting hygienic farm operations. The success of the initiative is greatly dependent on the farmers’ access to more specialized knowledge to prevent the indiscriminate use of antibiotics as well as adequate financial support and subsidized insurance to compensate for the losses in livestock farming to avert farmers from recuperating their losses through the means of antibiotic growth promoters.15 Reshaping farmers’ behavior, knowledge, and attitude is the only way to bring about sustainable change and healthy agricultural practices.

 

The destructive ambiguity of COVID – 19 has pushed the healthcare system to its limits , singlehandedly uncover ing the limitations of the public health sector . The health crisis shed light on the apparent need for global cooperation and underscored the need for more robust monitoring and regulatory mechanisms , particularly diagnostic technologies. As the world struggled to keep its feet on solid ground, the unparalleled nature of the pandemic has forced us to reposition our priorities in the sphere of public health , leading to detrimental effects on the global efforts and successes of antibiotic stewardship programs , which were put on an indefinite pause. Stewardship programs are only as strong as the support for them is, which is why it is paramount to visualize the pandemic and its effects on the surge of antimicrobial resistance through a syndemic approach to conceptualize the multifaceted opportunities for mutual learning. The resources and the expertise of antimicrobial stewardship programs can be efficiently used to develop antibiotic prescription and treatment protocols in COVID – 19 patients, control compliance with the guideline – concordant therapies, manage supply chain interruptions, and strengthen planning and response efforts. Furthermore, new monitoring systems that have been developed and implemented for COVID – 19 mitigation efforts can be harnessed and adapted to monitor the prevalence of AMR in the environment. As we are nearing the end of the pandemic and focusing on devising effective vaccine distribution strategies, we should not sit and wait for the time to reveal the true impacts of the virus on antimicrobial resistance and its unimaginable implications for both human and animal health and the environment. A “One Health” approach that will encompass hard-earned COVID-19 lessons , as well as integrated and conscientious collaboration between science and the political, social, and economic sectors should spearhead o ur global intervention strategies against antimicrobial resistance today.e

1. Nieuwlaat, Robby. “Coronavirus Disease 2019 and Antimicrobial Resistance: Parallel and Interacting Health Emergencies.” 16 Ju ne 2020. Web. 26 Jan. 2021.

2. Gilbert, P., & McBain, A. (2003, April). Potential impact of increased use of biocides in consumer products on prevalence of antibiotic resistance. Retrieved February 11, 2021.

3. Ventola, C Lee. “The Antibiotic Resistance Crisis: Part 1: Causes and Threat s.” P & T: A Peer – reviewed Journal for Formulary Management . MediMedia USA, Inc., Apr. 2015. Web. 26 Jan. 2021.

4. Dall, Chris. “Studies Highlight Dynamic Impact of COVID – 19 on Antibiotic Use.” CIDRAP , University of Minnesota, 28 Aug. 2020.

5. Monnet, D. L ., & Harbarth, S. (2020, November 12). Will coronavirus disease (COVID – 19) have an impact on antimicrobial resistance? Retrieved February 09, 2021.

6. Punjabi, Chitra D., and Theresa Madaline. Prevalence of Methicillin – Resistant Staphylococcus Aureus (MRSA) in Respiratory Cultures and Diagnostic Performance of the MRSA Nasal Polymerase Chain Reaction (PCR) in Patients Hospitalized with Coronavirus Disease 20 19 (COVID – 19) Pneumonia: Infection Control & Hospital Epidemiology . Cambridge University Press, 26 Aug. 2020 .

7. Morgan, W. (2020, April 17). Heavy use of hand sanitizer boosts antimicrobial resistance.

8. Duda, K. (2020, April 17). Understanding the main problems with antibacterial soap.

9.  Rangel, G. W. (2017, January 11). Say goodbye to Antibacterial Soaps: Why the FDA is banning a household item. Retrieved February 17, 2021.
 
10. El – Nahhal, Ibrahim & El – Nahhal, Yasser. (2020). Ecological Consequences of COVID – 19 Outbreak. 10.13140/RG.2.2.24 456.85769.
 

11. Nabi, Ghulam, Yang Wang, Yujiang Hao, Suliman Khan, Yuefeng Wu, and Dongming Li. “Massive Use of Disinfectants against COVID – 19 Poses Potential Risks to Urban Wildlife.” Environmental Research . Elsevier Inc., 9 July 2020

12. Sandoui, Ana. “The Effects of Antibiotic Use in Animals on Human Health and the Drug Resistance Crisis.” Medical News Today . 9 Nov. 2018. Web. 24 Feb. 2021.

 
13. Attwood, Sophie, and Cother Hajat. “How Will the COVID – 19 Pandemic Shape the Future of Meat Con sumption? Public Health Nutrition.” Cambridge Core . Cambridge University Press, 12 Aug. 2020. Web. 24 Feb. 2021.
 
14. “Pandemic to Spark Biggest Retreat for Meat Eating in Decades.” Bloomberg News, 6 July 2020. Web. 25 Feb. 2021.
 
15. Bandyopadhyay S and Samanta I (2020) Antimicrobial Resistance in Agri – Food Chain and Companion Animals as a Re – emerging Menace in Post – COVID Epoch: Low – and Middle – Income Countries Perspective and Mitigation Strategies. Front. Vet.Sci.7 :620. doi: 10.3389/f vets.2020.00620
 

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