COVID-19 Antibiotic Overuse Puts Stewardship Efforts at Risk

Many COVID-19 patients are getting antibiotics even when the drugs are unlikely to help, raising concerns about patient safety and antibiotic resistance, experts told MedPage Today.

That practice pairs with a recent GAO report highlighting the minimal progress of a major federal initiative to combat antibiotic resistance before the pandemic.

"It already is a huge problem," said Elizabeth Hirsch, PharmD, of the University of Minnesota, which has an Antimicrobial Stewardship Project under its Center for Infectious Disease Research and Policy (CIDRAP).

Antibiotic-resistant bacteria and fungi cause at least 2.8 million infections and 35,000 deaths nationally every year, according to a CDC report from November. Deaths were down 18% from 2013, but "the burden of antibiotic-resistance threats in the United States was greater than initially understood."

Researchers are now asking whether COVID-19 patients who are potentially getting unnecessary antibiotics will contribute to national overuse trends.

Overuse in COVID?

When practitioners first encountered the novel coronavirus, unaware of what they were facing, many treated patients with antibiotics; even now, until they get test results back, they often use antibiotics, experts said.

"It is prudent," Hirsch said. "It's hard when these patients present because they look like they have [bacterial] pneumonia."

Emerging evidence says antibiotics typically will not help COVID-19 patients unless they have bacterial co-infection. "But we still are giving them antibiotics," said Trevor Van Schooneveld, MD, a board member with the Society for Healthcare Epidemiology of America (SHEA), which recommends against the practice.

In an analysis of coronavirus studies, published online May 2 in Clinical Infectious Diseases, 72% of 2,010 COVID-19 patients received antibiotics in the hospital while only 8% suffered bacterial and fungal co-infection, researchers wrote. "No antimicrobial stewardship interventions were described."

"However, it is likely that rates of co-infection will differ between different areas of the hospital and levels of care," lead author Timothy Rawson, PhD, of Imperial College London, wrote in an email to MedPage Today. "For example, there are some reports of higher rates of co-infection in patients who die of COVID-19 on intensive care."

Van Schooneveld, medical director of the University of Nebraska's antimicrobial stewardship program, said he saw colleagues prescribing antibiotics to COVID-19 patients, contrary to guidelines established per what he calls "an aggressive stewardship program."

That trend is declining as leaders have developed and disseminated more detailed clinical guidelines, but he acknowledges "it's hard for ICU doctors to stop using antibiotics, because that's been their practice in the past."

In addition, early-pandemic guidelines elsewhere directed providers to give antibiotics for COVID-19 patients, "but everybody has rewritten their guidelines 15 times during the pandemic."

Michael Stevens, MD, who directs Virginia Commonwealth University's antibiotics stewardship program, participated in a SHEA podcast in April. "We can limit antibiotics for [COVID-19] patients," Stevens said. "It's certainly something we should be looking at," he added, noting that data do not show much co-infection with bacteria for COVID-19 patients.

Other Antibiotic Scripts Down

Data on whether antibiotics are being overused in COVID-19 are sparse. According to IQVIA, a data science firm that CDC relies on for its annual antibiotic prescribing and use reports, antibiotic use is evident among COVID-19 patients -- but a recent report showed a 45% drop in overall national antibiotic use between the first week of January and mid-April.

The company declined to share its data with MedPage Today, but report co-author Michael Kleinrock, research director with IQVIA's Institute for Human Data Science, said the drop was likely due to pandemic-induced medical system shutdowns.

"I'm kind of astonished at the extent to which [antibiotic use in] acute care has disappeared," Kleinrock said during a call that was monitored by an IQVIA spokesperson.

He added that the data do not indicate a "major ramp-up" in hospitals purchasing antibiotics, perhaps because of the temporary elective surgery decline.

The decline in overall antibiotic volume "doesn't mean we are doing better" with antibiotic stewardship, Kleinrock said. "It's inconclusive even if we know the numbers are way down."

Van Schooneveld, who said he is familiar with IQVIA data, said it is typically limited to purchase-level data. Such "databases are useful because they have a broad reach, but they don't account for fluctuations."

IQVIA's data do not factor in hospital census fluctuation that "can radically influence antibiotic use," for example. They also don't measure appropriate use.

Other typical antibiotic use sources do not have pandemic-era data available.

The Agency for Healthcare Research and Quality runs an antibiotic safety project, but data "aren't available during the current COVID-19 pandemic since many project participants are busy caring for an influx of patients," an AHRQ spokesperson said.

Data the CDC collects "are incomplete and infrequent," Mary Denigan-Macauley, PhD, a GAO healthcare director who co-authored its report, said in an email to MedPage Today. "Consequently, an analysis of national data on antibiotic use trends during COVID-19 won't likely be available for some time."

Even Before COVID, Federal Efforts Failing?

The GAO report on pre-pandemic antibiotic stewardship efforts cited failures to adequately address the nation's antibiotic resistance issue, after a 2-year performance audit.

Per a 5-year National Action Plan initiated in 2015, the CDC is leading several federal agencies. A 2014 executive order commands the Combating Antibiotic-Resistant Bacteria Task Force to annually update the President on topics including how to address Action Plan barriers.

But in its first four reports, "the task force did not identify plans to address barriers to expanding antibiotic stewardship programs or the collection of antibiotic use data," the GAO wrote. Until it devises those plans, "the federal government cannot assure that the country is prepared to overcome the urgent health consequences of antibiotic resistance."

Among ongoing challenges the CDC faces are low rates of hospital participation in CDC data collection programs and challenges with stewardship training, according to the report.

"In the United States we just don't have a good surveillance system for tracking this," Hirsch said.

"Participation in [the CDC system] is relatively poor," Van Schooneveld said. "That's one of the weaknesses we have. The CDC wants this data ... but collection is not the easiest or simplest thing to do."

Outpatient prescriptions did decline 5% from 2011 to 2016, according to the CDC's November report, and GAO's Denigan-Macauley noted outpatient settings account for 85% to 95% of national antibiotic use.

But CDC director Robert Redfield, MD, said in the November report that "antibiotic resistance remains a significant enemy."

Stewardship Difficult but Doable

Despite the GAO report, experts said now is not the easiest time to harp on antibiotic stewardship.

"The presentation to hospital with COVID-19 is very similar to bacterial infection and we currently have very few ways of differentiating the two," Rawson wrote. "It is very difficult to suggest that clinicians avoid starting antibiotics when a patient is admitted to hospital."

But Van Schooneveld warned that clinicians "don't want to forget to do what we already know is right when we are treating coronavirus. [Providers] will err on what they would consider is the side of safety and prescribe antibiotics. Whether that's really the safer strategy I think is debatable."

Cornelius Clancy, MD, of the University of Pittsburgh and a member of the Infectious Diseases Society of America (IDSA)'s antimicrobial resistance committee, said he is cautiously optimistic, assuming the pandemic has peaked.

"Now that places have had the experience [treating COVID-19], hopefully we won't get crushed over the next few weeks and months," he said, "and be able to more systematically apply stewardship."

Rawson's advice is to "focus on stopping inappropriate antibiotics early during the patient's admission. This requires the clinician to send appropriate diagnostic tests for all patients admitted with COVID-19. They must regularly review antibiotic prescriptions and stop them when there is little evidence of bacterial co-infection. Hospitals should not lose sight of the need to maintain antibiotic stewardship activity. ... This is important for the benefit of both COVID-19 and non-COVID-19 patients."

Judicious use of antibiotics is also important in light of shortages, Rawson and colleagues noted.

Other guidance on antibiotic stewardship during COVID-19 includes a guideline from Benedikt Huttner, MD, of Geneva University and colleagues, and a flagging system deployed by researchers at the Mayo Clinic.

But experts remain wary that antibiotics will be overused during the pandemic and will contribute to the nation's ongoing challenges with stewardship efforts.

"We are already facing this [pandemic] with so much antibiotic resistance," Hirsch said. "I do think we will see an increase."

"This is not a new problem. It's not going away," Van Schooneveld said. "It's really not been adequately addressed."

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