By Marie Rosenthal, MS

More than half of patients hospitalized with suspected COVID-19 in Michigan during the state’s peak months received antibiotics soon after they arrived, just in case they had a secondary bacterial infection. However, only a handful had a bacterial coinfection. 

Those who received antibiotics were more likely to be older, have lower body mass index measurements, and to show visible signs of infection on their chest radiographs. They also were more likely to be in more critical condition upon presentation to the hospital.

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However, testing showed that 96.5% of those who received antibiotics only had SARS-CoV-2 (Clin Infect Dis [Epub Aug 21, 2020]. doi: 10.1093/cid/ciaa1239). The 3.5% of patients who arrived with a bacterial coinfection were older, nursing home residents, and admitted straight to the ICU. 

Half of these patients died, compared with 18% without bacterial coinfections. The study demonstrated that faster testing and better understanding of infection risk factors could help hospital teams determine who those patients are, and spare the rest of their COVID-19 patients the risks that come with overuse of antibiotics, the researchers said.

“COVID-19 continues to teach us something new every day,” said Debra Goff, PharmD, FCCP, an infectious disease specialist at the Ohio State University Wexner Medical Center, in Columbus. “Several studies have found most patients do not have a bacterial coinfection.” 

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A team from the University of Michigan (U-M), VA Ann Arbor Healthcare System and St. Joseph Mercy Health Care System reviewed data from more than 1,700 hospitalized patients at 38 hospitals. The hospitals were part of Mi-COVID19, a massive statewide effort that launched within weeks of the first Michigan case of COVID-19 diagnosed on March 10. The goal was to leverage the power of multiple quality improvement efforts sponsored by Blue Cross Blue Shield of Michigan. During March and April, Michigan was one of the nation’s early hot spots, and the epidemiologists hoped the new data would help patient care teams. Inpatient COVID-19 treatment guidelines shared by Michigan Medicine, U-M's academic medical center, have been updated based on these results.

Antibiotic Use
In addition to widespread overuse of antibiotics, the study showed that hospitals varied widely in their use of antibiotics among people newly hospitalized for suspected COVID-19. In some, only one-fourth of suspected COVID-19 patients received antibiotics within two days of being hospitalized, while in others, nearly everyone received them.

As time went on, and COVID-19 testing turnaround time shortened, the use of antibiotics dropped—but was still too high, according to Valerie Vaughn, MD, MSc, the study’s lead author and a hospitalist who helped launch Michigan Medicine's COVID-19 ICUs.

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“For every patient who eventually tested positive for both SARS-CoV-2 and a co-occurring bacterial infection that was present on their arrival, 20 other patients received antibiotics but turned out not to need them,” Dr. Vaughn said. “These data show the crucial importance of early and appropriate testing, with rapid turnaround, to ensure appropriate use of antibiotics and reduce unneeded harm.”

The new study would not have been possible without the Mi-COVID19 registry, which includes detailed data from pre-, post- and in-hospital care on COVID-19 patients treated in hospitals of all sizes and kinds across Michigan.

Stewardship
Dr. Vaughn, who has studied and worked to improve antibiotic prescribing for hospitalized patients with pneumonia, noted that COVID-19 differs in important ways from regular pneumonia, so standard antibiotic stewardship techniques may not work.

For instance, many suspected COVID-19 patients were tested for procalcitonin (PCT) soon after admission to the hospital, because it’s often used as an early indicator of bacterial infection while doctors wait for more definitive test results.

Just more than half of those who had a bacterial infection plus COVID-19 had a high PCT reading. But so did 22% of those who did not have bacterial infections. However, a low PCT reading was almost certain to mean that the person didn’t have a bacterial infection, the researchers said.

However, elevated white blood cell counts were a good predictor of who had a bacterial infection.

“If PCT was low, it had a very high negative predictive value (98.3%), that is, was not a bacterial infection and the antibiotics were not needed,” said Dr. Goff, who was not a part of the study, but was asked to comment.

“However, if the ICU physicians were not believers of PCT before COVID, then it is not surprising that PCT levels were not used by some in the decision-making process of stopping antibiotics. That would explain the wide range (27%-84%) of antibiotic use across 38 Michigan hospitals,” added Dr. Goff.

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The faster the COVID-19 viral test results were in, the faster their antibiotics were stopped. Half were stopped within a day of a positive coronavirus test. The turnaround time for such tests decreased over time, with 89% getting their results within a day in May compared with 54% in March.

Most of the patients tested for bacterial infections did not have the test that examines the respiratory tract. This may be because these tests require health care workers to interact with patients’ airways—which can generate aerosols and risk transmitting the coronavirus—or because they require a sample of sputum, which most of the patients didn’t have because of the dry cough that typifies COVID-19.

“Since their SARS-CoV-2 infection explains their symptoms, we should all be more judicious with prescribing antibiotics unless we see signs of a bacterial infection,” Dr. Vaughn said. “We need better guidance to help clinicians figure out if the cause of a rapid decline in condition is due to cytokine storm or bacterial infection, and better antibiotic stewardship programs [ASPs] to support physicians in determining if they need to order antibiotics, and if so, for how long and with what tests for bacterial infection.”

Dr. Goff added: “I think antibiotic stewardship must work with ICU clinicians to make the decision to stop antibiotics by using all the tools in the toolbox, and that includes PCT, culture results, respiratory rapid diagnostic test results, and clinical signs and symptoms. It is important to remember every extra day of unnecessary antibiotics increases the risks of C. diff [Clostridioides difficile] and antibiotic resistance. The fundamentals of an ASP apply to every COVID-19 patient.”

The study undercounts the percentage of patients who received antibiotics, Dr. Vaughn noted, because it left out those who received azithromycin. Earlier in the pandemic, azithromycin combined with hydroxychloroquine was seen as promising for COVID-19 patients.

Patients who were transferred to another hospital as part of their initial COVID-19 stay were also omitted from the analysis.