CLN - Focus on Molecular Diagnostics

How to Approach Antimicrobial Stewardship After COVID-19

An interview with Elizabeth Palavecino, MD

Jen A. Miller

During the worst of the pandemic, clinicians threw everything at COVID-19 to try to save patient lives. That often included antibiotics. About 80% of patients hospitalized with COVID-19 received antibiotics between March 2020 and October 2020, according to the Centers for Disease Control and Prevention (CDC), even though fewer than 3% of patients showed any sign of a bacterial infection (www.cdc.gov/drugresistance/covid19.html). CDC noted this was likely due to difficulties distinguishing COVID-19 from community-acquired pneumonia when patients first arrived at a hospital. In addition, critically ill patients might have been treated for bacterial co-infections.

CDC is now devoting millions of dollars for local health departments to tamp down on improper antibiotic prescribing, including $120 million to departments in New York City, Los Angeles County, and 60 other jurisdictions, according to Bloomberg Law.

Laboratory medicine professionals play a crucial role in antimicrobial stewardship programs (ASP), and in ensuring appropriate antibiotic use. We spoke to Elizabeth Palavecino, MD, professor of pathology at the Wake Forest University School of Medicine, about changes she’s seen in ASP throughout her career, especially during the COVID-19 pandemic.

How have advances in molecular testing changed the approach to ASPs?

There is no doubt that molecular testing has improved antimicrobial stewardship. In our institution, when we started doing more molecular testing, we saw the impact of having results available to the clinicians much faster. They can decide on a therapy at almost the same time they are seeing patients.

We implemented the use of a multiplex panel for detection of organisms from positive blood cultures on a specific group of patients: those admitted to the hospital, especially the intensive care unit (ICU). The results were available shortly after growth was detected in the blood culture bottles 7 days a week, 24 hours a day.

Of course, if you send a result at 2 a.m., you really need somebody on the clinical side to evaluate the report and make a treatment decision. If the lab sent the result to the ICU, there was always a clinician available there who could make a therapeutic decision. That’s why, at the beginning, we focused primarily on those patients who could benefit the most. In our hospital, the use of rapid molecular testing from positive blood culture has led to rapid diagnosis and appropriate treatment of bacteremia.

Our goal is to test the right patients at the right time to ensure appropriate use of antibiotics. If we do a lot of testing on patients who are not having an infectious process, we get more chances of a false positive, and then that patient is going to be treated for something they don’t have.

How has COVID-19 affected ASP performance, and what have we learned for the future of ASPs?

COVID-19 impacted us a lot. At the beginning, we didn’t have reagents. Manufacturers dedicated all their resources to producing coronavirus tests. For other tests—syndromic panels, molecular testing—we didn’t have enough reagents, or we didn’t have the disposables needed to perform testing. We really had to prioritize when to use molecular testing for infections other than COVID-19.

Later, COVID-19 impacted us due to how long patients were in the hospital. Some were hospitalized for a long time, in the ICU and on ventilators. All these things are risk factors for getting an infection of a multi-drug resistant organism. If you look at the surge of COVID-19, that same curve is seen in prescription of antibiotics in the hospital.

That made things more difficult for us and ASP. Remember, we didn’t know a lot about COVID-19 at the time.

We have been focused on communication with providers and explaining how they can ensure appropriate use of antibiotics, and we are seeing significant improvement. We also know more about COVID-19 and how it behaves. For example, after people have a viral infection, they have a higher chance of getting a bacterial infection because the virus can damage tissue and interfere with the body’s defense mechanisms and with immunity. This is true for other viruses as well as for the SARS-CoV-2 virus.

So we still are in the process, now that we have learned more about the behavior of this virus, of educating our clinicians.

How do the unique qualities of molecular testing, such as speed, affect how the lab collaborates with clinicians, nurses, and pharmacists?

Every time I do a lecture on ASP for microbiologists and technologists, I always emphasize that we need to collaborate with multidisciplinary clinical teams. To do that, we must spend more time outside of the laboratory and participate in different institutional committees designed to improve the care of the patient.

We know exactly the testing that we can do, and whether there are limitations to these tests. Typically, the pharmacists in my program are the ones who understand that first. We usually do preliminary studies with them when we want to implement a new panel, then the ASP staff and I decide whether to use it. Next, we offer education to providers throughout the hospital.

We have education programs designed for medical students, residents, fellows, general practitioners, and specialists—each of those groups has unique needs. We educate the nurses, too, particularly on the collection of samples, as we need a good sample to provide the right answer for the patient.

Does integrating molecular tests as part of ASP require different types of interpretation from the laboratory?

Clinicians, nurses, and pharmacists need to be educated about the advantages and limitations of tests. To help with the selection of the best treatment for a particular infection, the lab adds comments in the microbiology report to help other healthcare professionals understand results. It is difficult to educate everybody. We have a large number of clinicians throughout our healthcare system. Physicians must continually learn about their own specialties. They’re not going to be as focused on laboratory medicine, so we need to translate what the results for a specific test mean. Adding comments in the reports has allowed us to provide education to a vast community of providers.

This is particularly important for those molecular tests performed for patients in ambulatory care settings. I don’t worry as much about interpretation for patients in the hospital, because I have my ASP group review results, especially for blood cultures, and provide consultation to the clinical team if needed.

But for something like a gastrointestinal (GI) panel, we try to tell a provider not to order that unless the patient has been sick for more than 7 days, because most mild GI infections are self-limited and the patient is usually going to get better within that time frame. We leave specific comments for these situations so that at the time of ordering, the provider can see the requirement for ordering the test, and if the test is positive, a comment is added for an interpretation of those specific results. This has helped a lot in ambulatory clinics where it is otherwise very difficult to educate everyone working there.

What are some of the ways that you see molecular testing improving patient care in the context of ASPs?

No doubt having rapid results, particularly PCR testing for bloodstream infections, has been a huge help because every hour you delay administering not only antimicrobial therapy but the right antimicrobial therapy, the patient has lower chances of survival.

Sometimes we have the identification of an organism coming from the blood culture, but we don’t yet have all the susceptibility testing. So, we publish our antibiogram with the rate of antibiotic susceptibility for each organism seen in our hospital. That way, all our providers can select empiric therapy based on pathogen identification, until the full susceptibility report is available, so they don’t have to start with a broad antibiotic.

What do you think will be the future ways that advances in molecular testing will improve patient care?

Years ago, I wrote an article about how we didn’t expect to see molecular testing performed outside the main laboratory. I was afraid of people performing these tests without the right experience and that they could cause cross-contamination. But COVID-19 really changed my perspective. We didn’t have any other choice but to provide molecular testing in other clinics. We trained them, validated the tests, then monitored how they were doing. We didn’t have any problems during the pandemic with cross-contamination.

In the future, we need to have more molecular tests at the point of care. These tests could quickly diagnose some of the most frequently encountered infections and rule out things like SARS-CoV-2, group A Streptococcus, and influenza A and influenza B. Several test manufacturers have also added respiratory syncytial virus, as there has been an increase in cases of infection. Home testing also will continue. All of these advances can help decrease the likelihood of inappropriate antibiotic prescribing.

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