Since the 1940s, antibiotic resistance has vexed scientists, researchers, and the general public. The widespread usage of penicillin in World War II first propelled microbe evolution, resulting in the rise of numerous bacterial species resistant to the antibiotic [1]. Microbial infections caused by superbugs are extremely problematic; their difficulty to treat lies in their ability to bypass previously effective drugs.
Throughout the past decades, however, this public health crisis has been neglected by researchers and physicians alike, allowing bacterial and fungal microbes to grow increasingly resistant to the drugs designed to kill them. New research shows that the COVID19 pandemic has exacerbated the threat that antibiotic resistance poses to public health, and our narrow lead in the race against superbug evolution may cease to exist by the time this pandemic draws to a close.
The relationship between COVID-19 and antibiotic resistance may not seem evident at first — antibiotics are used to treat bacterial and fungal infections, while COVID-19 is caused by the SARSCoV-2 virus. However, one significant danger posed to a COVID19 patient is the risk of developing a co-bacterial infection, such as bacterial pneumonia [2]. Co-infection, which can significantly increase the patient’s mortality rate due to their already weakened immune system, requires antibiotic treatment [3]. Hospitals are also one of the easiest places to contract an antibiotic-resistant infection, as they are consistently prescribing antibiotics to patients and promoting the evolution of superbugs [4]. When antibiotics are used in such a prevalent manner, however, severe long-term consequences may emerge.
One systematic review reports that 72 percent of hospitalized COVID-19 in the U.S. and China received antibacterial therapy. However, only 8 percent of those who received antibiotics had a bacterial or fungal infection [5]. This data suggests that antibiotics were distributed to patients despite a lack of evidence for a co-bacterial infection. In another study on patients in Michigan hospitals, the rate of bacterial co-infections was 3.5 percent. Yet, 56.6 percent of patients were prescribed antibiotics prematurely [6]. This overuse of antibiotics is the result of physicians’ attempts to prevent fatal bacterial co-infections, but in the long run, antibiotic misuse can propel the development of antibiotic-resistant superbugs. Bacteria that are antibiotic-resistant have the ability to neutralize antibiotics, pump out the antibiotic from their bodies, or redirect the antibiotic to target another site such that it does not affect cell function. Because these bacteria are essentially immune to known antibiotics, they survive and multiply rapidly, eventually allowing that general bacteria population to evolve into an antibiotic-resistant one [7]. This evolution sets off a chain reaction that prompts the growing superbug population and the inability to successfully treat infected patients.
History repeats itself. This isn’t the first time we’ve witnessed a sharp increase in antibiotic use during a viral outbreak, followed by an increase in antibiotic-resistant infections. During the 2002- 2004 SARS pandemic, it was reported that doctors used antibiotics as a first line of defense in Hong Kong. The usage of carbapenem — the strongest type of antibiotic used for high-risk bacterial infections — increased by 73 percent during the outbreak [8]. After the pandemic subsided, hospitals noticed a rise in the number of bacterial infections that couldn’t be treated with carbapenem. In a retrospective study conducted on influenza cases from 2005 to 2009, it was found that 80 percent of patients who were prescribed antibiotics did not actually have a diagnosis for bacterial infection [9]. Antibiotic misuse during the Ebola outbreak from 2014 to 2016 was also documented and cautioned against, with reports of an Ebola patient being sent home with antibiotics for his “low-grade, common viral disease” [10].
The methods used to treat SARS, influenza and now COVID-19 patients have amplified the existing crisis — antibiotic resistance is skyrocketing. As of July 2020, the CDC reports that 2.8 million people in the U.S. catch an antibiotic-resistance infection, while 35,000 people die from these infections [11]. Even as antibiotic resistance grows, however, large pharmaceutical companies such as AstraZeneca and Novartis are gradually abandoning antibiotic research due to a lack of financial incentive. Research and development require an immense amount of time and resources, and the cost-benefit ratio seems far too high. With a multitude of factors contributing to antibiotic resistance, it is evident that more action must be taken in the race against superbug evolution. However, the question that has stumped us for years remains: how exactly do we combat antibiotic resistance?
Reflecting on the events of COVID-19 and past SARS pandemics, one way of fighting antibiotic resistance might include finding alternative methods to treat viral outbreaks with a limited arsenal of antibiotics. One alternative method includes PPMO, which are synthesized forms of DNA and RNA with the ability to silence gene targets. In contrast to antibiotics, which disrupt bacterial cell function, PPMO interferes with bacterial genes directly. Researchers state that PPMO must undergo testing for toxicity before it is used in humans, but that its mechanism shows promise [13]. Specialists have discovered phages that target C.diff, a prominent superbug in hospitals. The phages are viruses that seek bacteria as a host and inject their DNA, subsequently replicating and destroying the bacterial cell in the process [13]. Phage therapy is advantageous as it is specific for a target bacterial population, but it is still prone to antibiotic resistance [14]. Probiotics have also been found to potentially modulate gut microbial composition to expand the “good” bacteria population. The field of gut microbiota is relatively unexplored, however, and the precise mechanisms of probiotics acting on host health are unknown [14].
Additionally, incentivizing pharmaceutical industries to innovate new drugs could aid in the fight against antibiotic resistance. A proposed method suggests shifting the economic mechanisms involved in the funding of research. The “Netflix model,” a model in which companies receive an up-front payment in the early development of research, has shown promise in motivating firms to continue antibiotic research [15].
Catalyzed by the effects of the COVID-19 storm, the lingering effects of past viral pandemics, widespread antibiotic misuse, and the reluctance of big pharma to continue antibiotic research, antibiotic resistance poses a greater threat to public health than ever. It has always been a concern lurking under the surface, but the presence of the pandemic has given it the potential to emerge and bring upon a wave of damage.
The COVID-19 pandemic has taught us that it is imperative to be aware of what antibiotic resistance will look like in the next few years and that it is time to fight it head-on. The COVID-19 pandemic may slow down and gradually reach its end, but the antibiotic resistance public health crisis is far from over — instead, it is a ticking time bomb.
References:
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