4
May
2020

If We’re Smart, COVID19 Will Strengthen Our Defense Against Drug-Resistant Bugs

Vidya Atluri, MD PhD, infectious disease fellow, University of Washington Medical Center

The COVID-19 pandemic makes it clear that infectious diseases can devastate the world with remarkable speed. But long before this crisis, we were fighting another infectious scourge below most people’s radar – antimicrobial resistance.

One estimate by the CDC in 2013 found that 2 million people in the US get infected with drug-resistant bacteria, leading to a huge toll of suffering, death, and economic cost. These infections can strike anyone, any time, and the problem is global in scope. Bacterial infections like tuberculosis, pneumonia and salmonella are becoming harder to treat as these bugs and others evolve and evade our current arsenal of antibiotics.

Paul Pottinger, MD. Director of the Infectious Diseases & Tropical Medicine Clinic at University of Washington Medical Center; University of Washington professor of Medicine and Allergy and Infectious Diseases; Director of UWMC’s Antimicrobial Stewardship Program

Our main weapon in that fight: antibiotic stewardship, meaning the right drug for the right bug for the right duration. If we aren’t careful in how we use the antibiotics we currently have, we face the risk of drug-resistant bacterial infections that could leave another brutal mark on our society.

Although our resources are understandably diverted to rise to the challenge of coronavirus, the fight against antimicrobial resistance continues. COVID-19 presents many obstacles, but also opportunities.

If we as physician-scientists take the initiative, and proceed deliberately — not impulsively changing standard of care based on every anecdotal report — we will emerge with a stronger, more impactful public health system that responds to both viral pandemics and the long-neglected, emerging disaster of bacterial drug resistance.

The Right Bug

Antibiotics don’t treat viruses. This is basic knowledge for almost everyone at this point, not just physicians. And yet … the majority of viral respiratory infections are treated with antibiotics.

Why? Diagnostic uncertainty. How do clinicians know if an infection is viral … or bacterial … or bacterial after viral? Or … does this patient even have an infection at all?

Diagnostic uncertainty is the fundamental driver of inappropriate medical antibiotic use, aka overprescribing.

Long before COVID-19, the solution has been either giving antibiotics to patients at highest risk for complications or “watchful waiting.” That means avoiding antibiotics unless things get worse. Neither solution is ideal. And, neither should be acceptable.

The market has already responded with very reliable molecular testing for respiratory specimens. The technical performance of these assays is superb, and their turnaround time is short … and yet, their cost and regulatory concerns prevent them from being deployed in every medical office in the nation. Some insurance plans will cover this expense, but many will not … and only some offices are willing to take on the burden of ensuring they are CLIA-approved to perform these assays on-site.

If we are savvy, the pandemic will lead us to fix this problem. The massive buildup of a  network of point-of-care rapid testing platforms could be leveraged for use against SARS-CoV-2, but also for other respiratory infections long after this pandemic is gone. In this case, this federal investment could pay off in unseen ways for decades to come.

The other exciting development that shows promise is self-administered at-home viral respiratory testing. It has performed spectacularly here in the Pacific Northwest (initially through the Seattle Flu Study, now retooled against COVID19 under the new name of SCAN).

Using the nation’s rapid parcel delivery infrastructure to get specimens to reference labs is no longer a pipe dream. Everyone knows Amazon can get a package to your doorstep in a day. The general public intuitively gets that they can take advantage of this capability by taking a sample at home and shipping it to a lab. The urgency to do this kind of testing is clear. In the near term, our goal must be to diagnose COVID-19 correctly right away, because these patients are at high risk for getting antibiotics they may or may not need … which will further exacerbate our systemic pre-existing problem of breeding antimicrobial resistant (AMR) organisms.

On the other hand, the emphasis on COVID-19 within the community and healthcare settings leads to encounters focused on one question: “Does this patient have COVID-19?”

Answering that question, without going on to “What else might this patient have?” may lead to premature diagnostic closure. By focusing on COVID-19, we can miss our opportunity to treat other infections, from flu to strep throat. While most of those patients will recover on their own (hence the success of “watchful waiting”), some will go on to have complications, which may require longer durations of antibiotics than if the patient had been treated early on. The longer you have to take a course of antibiotics, the greater the opportunity for the bacteria to develop resistance to the drug.

The Right Drug

The response to COVID-19 has included the quest for an effective medical treatment. In some cases, we have proceeded thoughtfully by conducting well-designed, randomized, controlled trials. In other cases … not so much.

Time is a precious resource in a pandemic, and if physicians are acting too much in the moment based on the latest anecdotes or published case series or yesterday’s hunch, then they’re spending time that could be better used by enrolling patients in a well-designed clinical trial that could give us solid evidence to act on in a couple months.

Although our hunger to help is palpable—and very understandable—the rush to publish or espouse unproven claims might have very real adverse effects. As we have learned the hard way, time after time, the disciplined response often turns out in the end to be the best response. An oft-repeated mantra in antimicrobial stewardship is, “Don’t just do something… stand there!”

This is true whether we are considering treating a mild infection with antibiotics, even if we feel that treatment is unnecessary, or whether we are considering using an experimental agent in an unproven manner. In antibacterial drug stewardship, of course, the concern is that our injudicious use will accelerate resistance.

A similar concern relates to respiratory viral infections: During the 2009 H1N1 “swine flu” pandemic, the antiviral oseltamivir (marketed by Roche as Tamiflu) was used indiscriminately, and this was associated with genesis of drug-resistant influenza.

It is too soon to know whether COVID-19, another RNA respiratory pathogen, will develop resistance to treatments to come, although this question is very much on our minds now in light of the happy news that remdesivir is approved for administration to severely ill patients under an emergency use authorization.

Will this drug be used willy-nilly? We certainly hope not, and the EUA mechanism may help protect against that… for now. Time and again, out of our eagerness to help patients, we medical professionals have over-prescribed antibacterials, and that pattern may play out in the case of whatever treatments are (we hope) ultimately proven to help in COVID-19.

Overprescribing of an antiviral could have serious consequences. One of the strange features of COVID-19 is that treating a virus may have collateral damage in terms of increasing antibacterial resistance, if the antibiotic azithromycin is commonly prescribed in combination. To be clear: If randomized trials support its use, then we are all for that! Outside of trial use, we do have concern for this practice, not only for its potential to drive resistance but also because of possible cardiotoxic side effects.

The Right Surveillance

Antimicrobial stewards have long worried about the amplification of resistant bacteria in skilled nursing facilities, assisted living facilities, and long-term acute care centers. The patients tend to be elderly and infirm, with multiple co-morbidities, and frequently are treated for respiratory or urinary infections (probably too frequently).

Now, enter COVID-19, which has a strong predilection for this exact same patient population, often with lethal results. Surveillance testing of workers and residents of these facilities has revealed that some have a strikingly high prevalence of SARS-CoV-2 viral PCR test positivity, suggesting that this group remains at risk and may serve as a reservoir of infection for prolonged periods of time.

What if surveillance could be expanded to include multi-drug-resistant gastrointestinal or genitourinary colonization? It would only take a simple extra step of sample collection. Could the knowledge gain enhance infection control practices, and guide prescribers in their choice of antibiotics for those who need to be treated? Bringing surveillance to this at-risk population is an attractive opportunity.

The Right Tools

COVID-19 has ushered in telemedicine, with a vengeance. We applaud that. It’s about time! The desire to help patients avoid healthcare settings has led to an incredible increase in remote medical visits, potentially increasing access in underserved areas, especially rural areas far away from major hospitals.

The effect of remote visits on antibiotic prescribing is yet to be determined. Perhaps the ease with which these visits can occur will decrease the impulse to prescribe an antibiotic in order to make patients feel like they got something for their trouble of spending time driving to the clinic, sitting in traffic, finding a place to park, etc. On the other hand, the inability to truly examine the patient physically in person could increase antibiotic prescribing “just in case” the reported symptoms are being caused by some unknown bacteria. Better remote medicine capabilities could also enhance collaborations between healthcare workers in the farthest corners of the world – to help them make better choices, which will protect us all.

This epidemic has taught us that we are all connected, and microbes don’t respect boundaries of any kind. We need to cross boundaries even faster.

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