Superbugs were already on the rise. The pandemic likely made things worse.

According to public health experts, antibiotic misuse and overuse during the pandemic could exacerbate another ongoing crisis: antibiotic resistance, in which pathogens such as bacteria and fungi evolve to resist powerful drugs designed to kill them.

Antibiotic-resistant diseases kill more than 750,000 people each year, with the figure expected to rise to 10 million by 2050. Antibiotic-resistant bacteria can cause about 2.8 million infections and over 35,000 deaths in the United States alone each year.

Antibiotic overuse during the COVID-19 pandemic may now be compounding the situation. When COVID-19 author describes coughing, fever, shortness of breath, and chest X-rays indicated white spots—lung inflammation resembling bacterial pneumonia—many were offered antibiotics in the early months of the pandemic. For example, more than half of the approximately 5,000 patients admitted to hospitals in the United States between February and July 2020 were given at least one antibiotic within the first 48 hours of their stay.

"When dealing with uncertainty, you err on the side of prescribing, which isn't always the best thing to do," says Jacqueline Bork, an infectious disease physician at the University of Maryland Medical Center.

Antibiotics are only effective against bacteria, not viruses such as SARS-CoV-2, which causes COVID-19. However, pneumonia can be caused by fungi, bacteria, or viruses. Identifying which pathogen is to fault can take up to 48 hours and may need invasive tests to determine the infection's source. Sometimes the tests fail to identify the cause of the problem. "It's likely that many of us were overprescribing antibiotics. But, given the absence of a clear understanding of the situation, we did the best we could at the time," Bork says.

Some doctors were also concerned that, as with influenza and other viral infections, a fungal or bacterial infection could develop during or following COVID-19. "We couldn't even screen for viral versus bacterial illness at first because there were so many people who came in with pneumonia," Bork explains.

When she and other doctors across the world discovered that only about 20% of COVID-19 patients had fungal and bacterial co-infections, they reduced their antibiotic use. Antibiotics were required for patients who were critically ill. They were in hospitals for more extended periods, often with breathing tubes and catheters that cause bacterial infections and sepsis.

Despite this, doctors in many parts of the world continued to provide antibiotics to COVID-19 patients who didn't need them. Patients had resorted to self-medicating with antibiotics when they could not consult doctors, sometimes even as a preventive step. Overuse and misuse of antibiotics may have occurred during the pandemic due to the high cost and lack of access to diagnostic tests that establish bacterial illness and hence the necessity for antibiotics, a "just-in-case" attitude, and sometimes a lack of knowledge about the latest science.

How does antimicrobial resistance develop

Antibiotics are chemicals produced by soil-dwelling fungi and bacteria that kill or hinder the growth of other bacteria competing for the same limited resources. The targets adapt over time by developing resistance against such an arsenal. They accomplish this by producing enzymes, which inactivate antibiotics, drain antibiotics from bacterial cells, block antibiotic entry, or bypass their effects. Other bacterial species that weren't primarily aimed by antibiotics can sometimes evolve defenses by acquiring relevant genes from nearby resistant bacteria through a process known as horizontal gene transfer.

Researchers have developed commercial antibiotics based on natural antibiotics that fight bacterial illnesses in humans and animals. However, some of these infection-causing bacteria in water and soil may have already gained resistance genes.

Such resistant bacteria make up a small percentage of the bacterial population in host bodies at first, but this changes as antibiotic use increases. The medicine kills susceptible bacteria, eliminating competition and allowing resistant germs to proliferate and thrive quickly. In addition, giving incorrect antibiotic doses or misusing them, such as for the wrong condition, can kill healthy bacteria in our bodies and foster the spread of antibacterial drugs superbugs.

These drug-resistant bacteria can spread by sewage, polluted water, surfaces, and food—or through direct contact—in hospitals, communities, animals, and poultry farms. As more individuals become infected with superbugs, current antibiotics become less effective, resulting in more extended hospital stays, more medical costs, and more deaths. This is especially concerning for low- and middle-income countries, which are disproportionately affected by limited access to clean water and sanitation, quality healthcare, and over-the-counter access to generic antibiotics, encouraging self-medication when consultation is costly.

How COVID-19 may exacerbate multi-drug resistant infections

During the pandemic, 35 of 56 nations reported an increase in antibiotic prescribing, according to a global survey done by the World Health Organization in late 2020. Antibiotics were prescribed in practically all COVID-19 instances in one country, and self-medicating with these drugs was widespread in another.

Antibiotics such as azithromycin, doxycycline, fluoroquinolones, cephalosporins, and carbapenems have been prescribed to COVID-19 patients in hospitals. Although some studies have shown that bacterial or fungal co-infection or secondary infection rates among COVID-19 patients are less than 20%, they've frequently utilized broad-spectrum antibiotics that kill a variety of bacteria, including helpful bacteria. Antibiotics such as azithromycin and doxycycline have been prescribed to outpatients with mild COVID-19 symptoms.

A few studies suggested taking azithromycin and doxycycline early in the pandemic because of their antiviral and anti-inflammatory properties, which could help calm a COVID-19 patient's hyperactive immune system when it starts destroying its cells. However, more recent research has found no real benefits.

"A lot of COVID-19 patients come to me for a second opinion, and I see azithromycin on their prescriptions even now," says Lancelot Pinto, a pulmonologist at Mumbai's P.D. Hinduja Hospital. "Perhaps the justification is that there's a chance of a bacterial infection, so it's better to be covered," she says, "but I don't think many physicians [in India] care if it's a virus or not when prescribing antibiotics."

In other cases, physicians have been compelled to prescribe azithromycin in remote areas where, for example, diagnostic testing such as X-rays are unavailable to confirm pneumonia, let alone determine whether the etiology is bacterial, fungal, or viral.

"When individuals aren't as sure of themselves, they think it's better to provide it just in case," says Rumina Hasan, a pathologist at the Aga Khan University in Karachi, Pakistan. She also points out that disconnected physicians or unable to keep up with current COVID-19 information contributed to the improper overuse of antibiotics during the epidemic. "And it's tough to change a trend [of using certain treatments against a disease] once it's established," Hasan explains.

Antibiotics can save lives when used correctly, but global health experts believe that their extensive and indiscriminate use during the epidemic may have produced the perfect storm for resistant bacteria to emerge.

In the future

We may not see the rise of superbugs and their effects right away, but "the harm is done," says Pilar Ramon-Pardo, Pan American Health Organization's regional advisor on antibiotic resistance. During the pandemic, the WHO's Global Antimicrobial Resistance and Use Surveillance System took a hit due to a shortage of medical staff worldwide who could collect samples and report on drug-resistant microbes.

There's a budget shortage, and mental fatigue as all resources are devoted to defeating COVID-19. "People don't want to hear about yet another public health crisis," says Muhammad Zaman, a Boston University, professor of biomedical engineering. "Something has to give," says the speaker.

Should we expect new antibiotics to fight antibiotic-resistant illnesses if they become more common in the post-pandemic world? According to Zaman, there aren't likely to be as many. Antibiotic courses are rarely longer than 14 days, and they don't earn pharmaceutical companies as much money as therapy for common diseases like cancer and diabetes. New drugs are also more likely to encounter drug resistance sooner rather than later, making innovation less lucrative.

The National Institutes of Health, on the other hand, created an antibacterial resistance initiative in 2013 to conduct and fund research aimed at evaluating novel medications and diagnostic tools as well as improving the use of existing antibiotics. According to global health experts, the solution is to improve infection prevention and control. Vaccines against drug-resistant diseases that are now being developed could also be promising.

"However, the idea that this is merely a scientific issue is both incomplete and misleading," Zaman argues. "We need to consider economics, availability, and human behavior."

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