The COVID-19 pandemic is currently coinciding with the flu season and several states and areas of the world are experiencing upticks in new cases. While hospitals have some experience with COVID to go on, some experts are concerned that how doctors are administering antibiotics during the COVID-19 crisis could potentially make the fight against antimicrobial resistance harder. Data from early in the pandemic suggests that the majority of COVID patients are given antibiotics when potentially less than a tenth of them needed it. That could spell disaster if the trend continues.
What is antimicrobial resistance?
Antimicrobial resistance (AMR) occurs when microbes are no longer affected by antibiotics. Doctors can run out of options if a patient comes in with a bacterial infection that is resistant to all available antibiotics.
Part of the issue with AMR is that we are running out of antibiotics that can work against bacteria and other microbes that have developed resistance. Think about it as evolution on a fast track. At first, the antibiotics may kill all or most of the microbes present in a population. But if a few can tolerate the antibiotic and live on, that can allow it to grow into a resistant population that won’t be affected by the antibiotic in the future.
If that strain of the microbe persists, it could become the dominant form that is passed around and infect people. And when those people land in the hospital, doctors may not be able to effectively treat them and they may die from their infections.
The “superbug” crisis has been building for a long time. Increasing resistance is also in part due to antibiotics being heavily used in certain types of agricultural and livestock raising practices. The Centers for Disease Control and Prevention (CDC) published a report in 2016 that estimated “at least 30 percent of antibiotics prescribed in the United States are unnecessary.” In 2019, the World Health Organization estimated that by 2050 AMR could cause 10 million deaths a year.
Without antibiotics that we can count on, we could go back to dying from infected cuts and surgeries will be much more dangerous. “We take antibiotics for granted,” says Steffanie Strathdee, professor of medicine at the University of California, San Diego, to Changing America. “We really are entering an era where a simple surgery like C-section or hip or knee replacement can end up an infection that’s untreatable.”
AMR could become a more urgent crisis than COVID-19. “I don’t think I’m exaggerating to say it’s the biggest human health threat, bar none. Covid is not anywhere near the potential impact of AMR,” says Paul De Barro, who is the biosecurity research director at Australia’s national science agency, the CSIRO, to The Guardian. “We would go back into the dark ages of health.”
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Why this matters for COVID-19
The COVID-19 pandemic has been shining a light on many issues, including how unprepared the country was for a public health emergency and its disproportionate effect on marginalized communities. A study that looks at reports from 2019 through April 2020 found that about 72 percent of COVID patients received antibiotics while only about 7 percent of patients overall had bacterial infections. A study of ICU patients over a one-month period of time suggests that there is no difference in mortality if early antibiotic treatment is given or not. Another analysis of data from more than 1,700 patients in Michigan found that between March and June about 56.6 percent were prescribed early antibiotic treatment while 3.5 percent had confirmed bacterial infections.
This could have major implications for fighting AMR alongside COVID. Patients in the hospitals are always at risk of hospital-acquired infections. The CDC estimates 1 in 31 hospital patients could have a health care-associated infection on any given day. “It’s pretty common knowledge due to this fear of secondary bacterial infections as a result of COVID that antibiotic stewardship as we call it is going out the window,” says Strathdee. “There’s a lot more prescribing to try to prevent these infections, even if there’s a low chance of them occurring.”
Pharmacist and antibiotic resistance expert Ravina Kullar agrees that antibiotic stewardship, which she defines as giving the right drug to the right patient at the right time at the right dose, has fallen off the priority list. “Many people are receiving inappropriate antibiotics when in fact they do not have a bacterial infection. The progress that we have made will be useless if we continue on this trajectory,” she writes in an email to Changing America.
What we can do about AMR?
There are strategies to combat antimicrobial resistance. Besides searching for or developing new antibiotics, one strategy is antibiotic stewardship that involves coordinated and controlled use of antibiotics. Hospitals can set up their own antibiotic stewardship programs that promote optimal antibiotic use, educates their staff and advances that science around antibiotic use.
Another strategy to use in parallel with antibiotic stewardship is phage therapy. Phages or bacteriophages are bacteria-specific viruses that occur naturally. They can be harvested and cultivated for use against the bacteria that they feed on.
Humans have known about phages at least since 1917, but they were temporarily forgotten about by modern medicine. The advantages to phages is that there are tons of different phages out in the world and it could take less time and money to make them into treatments. “I was becoming increasingly frustrated that the drugs I was working on in the US, which typically cost $1bn to develop, were not accessible to most people living in developing countries,” says Tobi Nagel of Phages for Global Health to The Guardian. “Phages could be made into drugs in less than 10 years.”
Strathdee has personal experience with phage therapy and its potential to save lives. Her husband acquired a bacterial infection while traveling and returned to the U.S. The doctors ordered testing and the type of bacteria he had was resistant to 15 different antibiotics from the start, according to Strathdee. Eventually, the doctors ran out of options. Strathdee read about phage therapy and how that could help fight infections. They decided to try it, were able to get a hold of the right phages and his life was saved, later written into a book titled “The Perfect Predator.” But phage therapy is still in early stages and not as well funded as other activities like antibiotic development.
Although phage therapy is not meant to be the sole solution to AMR, it is one piece of the puzzle in the fight. Another piece is being able to know what we are fighting against, and that’s by being able to identify microbes. “Diagnostics and diagnostic stewardship are critical as the holy grail for tackling AMR, especially as timely and accurate diagnosis will also improve antimicrobial stewardship,” pharmacist Esteller Mbadiwe, who is Founding Partner of Ducit Blue Solutions, writes in an email to Changing America. “There should be a core stewardship triangle that includes the expertise of clinicians / prescribers, the laboratory teams for their diagnosis expertise and the pharmacy teams as the medicine experts, as well other healthcare professionals.”
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Although diagnostics exist for microbial infections, it could be quicker and more accessible. Costs of tests are a barrier that hospitals have to weigh against other budget needs. Consequently, because we don’t have a point of care diagnostic tool that’s inexpensive and widely available, doctors may make a presumptive diagnosis and prescribe antibiotics before they know for sure if there’s a bacterial infection, says Strathdee.
Part of how COVID complicates this is that some of the symptoms associated with COVID are similar to pneumonia. So even if there are diagnostic tests for bacteria present in the lungs or types of bacterial pneumonia, that may not help with diagnosis and piecing out what is actually causing illness in the patient, explains physician Jasmine Marcelin at the University of Nebraska Medical Center. The way it looks on imaging like a chest X-ray or CT scans could easily be COVID-19 or it could be a bacterial pneumonia.
Anecdotally, Marcelin has seen COVID patients develop bacterial resistance. But it’s hard to know if they already had this organism hiding out in their lungs prior to their COVID diagnosis, she notes.
The long view on COVID and AMR
Although there is some data to suggest doctors were giving antibiotics to COVID patients too often at the beginning of the pandemic, that does not mean it is still the case right now. In the coming months, Marcelin hopes to see long-term data on antibiotic use during the pandemic and whether or not we have people that are developing resistance over the course of a hospitalization. She is also hoping to be better able to figure out some of the clinical implications of the tests in the context of COVID that look for inflammation or other types of markers and how closely they correlate with a person’s likelihood of developing a bacterial infection throughout the course of their disease.
We also know that there are disparities and inequities in COVID hospitalizations and cases and deaths among Black, brown, indigenous and other people of color, and Marcelin is also interested in seeing how those disparities play out in antibiotic use as well.
Hospital-acquired infections are still a problem, and coinfections with COVID remain a valid concern. “I have absolutely no doubt that in 20 or 40 years, we will look back at healthcare as it was implemented in 2020 and shake our heads in wonder about how they could have let so many infections spread in healthcare facilities,” says former CDC director Tom Frieden to Insider. “We’re just not anywhere near where we need to be in terms of infection prevention and control.”
Better collaboration and coordination could help the situation. In Nigeria for example, the COVID-19 pandemic has seen strengthened coordination among agencies and “this needs to be sustained to tackle AMR,” writes Mbadiwe. “There have been a lot of lessons learnt globally and we need to look at the data to inform decisions going forward. There is a need for strengthened data and capacity building across Africa, in other proffer solutions for us, by us in a holistic manner.”
There’s also concern that shifting resources and attention to dealing with COVID-19 may lead to falling behind on other public health issues. The term for this is “exceptionalism,” explains physician and journalist Seema Yasmin. “We saw the same thing happen with Ebola in 2014 to 2016 where resources were diverted away from other disease areas to tackle the Ebola epidemic,” says Yasmin. “And then we saw an increase in maternal mortality in TB and HIV as a consequence.”
Strathdee coauthored a commentary in The Lancet with Sally Davies and Marcelin calling attention to AMR in the context of the coronavirus. They write that “the path forward is not only one that builds back from the COVID-19 pandemic, but also addresses AMR in the context of pandemic preparedness.”
Currently in the U.S., there are two pieces of legislation that have been introduced in Congress regarding AMR. They are the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act and the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act. The DISARM Act creates incentives to monitor antibiotic use and report data to the CDC and the PASTEUR Act supports the development of new antibiotics.
Overall, there could be more communication about AMR. There needs to be re-education of antibiotic stewardship practices for clinicians and the public, writes Kullar. “We really need to raise awareness of the superbug crisis but also the dearth of antibiotics in the pipeline,” says Strathdee. “As well as the fact that we have something like phage therapy that has been there all along.”
Kullar writes, “Now is THE time we all as a nation have to step up with antibiotic stewardship so that our children and our children’s children will have antibiotics available!”
For up-to-date information about COVID-19, check the websites of the Centers for Disease Control and Prevention and the World Health Organization. For updated global case counts, check this page maintained by Johns Hopkins University or the COVID Tracking Project.
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