Broad-Spectrum Antibiotic Use Questioned in Intensive Care

Ingrid Hein

October 17, 2019

"I don't think we should be withholding antibiotics from our sickest group of people," said Angel Coz Yataco, MD, from University of Kentucky Healthcare in Lexington.

Coz Yataco, who is a member of the Surviving Sepsis Campaign, will be speaking in favor of the immediate administration of broad-spectrum antibiotics for all sepsis patients at the upcoming CHEST 2019.

Antibiotics need to be administered to all sepsis patients without delay. Evidence has shown that in the 6 hours after the onset of hypotension, delays in antibiotic administration increase mortality by 7.6% every hour (Crit Care Med. 2006;34:1589-1596).

"If I was a patient with sepsis, I would want broad-spectrum antibiotics early," said Coz Yataco, who is one of the authors of an argument for the administration of broad-spectrum antibiotics published this month in CHEST (2019;156:645-647).

"I would not want my physician to wait for more information, knowing that the longer I wait, I have a much higher chance of dying," he told Medscape Medial News. Then, 1 or 2 days later, when more information about the infection is available from cultures or it becomes clear that a patient has been misdiagnosed, "we can peel off as many antibiotics as we can."

This is in line with the Surviving Sepsis Campaign guidelines, which recommend the administration of broad-spectrum antimicrobial therapy covering all likely pathogens within 1 hour of sepsis recognition. The campaign also recommends measuring lactate levels, obtaining blood cultures, treating hypotension, and applying vasopressors.

"Sepsis is lethal. Most people would agree this is a better strategy than just waiting for information," Coz Yataco said.

But going broad is not always a good idea, according to Jayshil Patel, MD, from the Medical College of Wisconsin in Milwaukee, who will argue at the meeting that research in this area is flawed and greater scrutiny is needed because broad-spectrum antibiotics can harm some patients.

"A lot of times, we don't know what the source of the infection is," noted Patel, who cowrote a counterpoint to the suggestion (CHEST. 2019;156:647-649).

For younger patients, broad-spectrum antibiotics could ultimately lead to harm. "If we implement a one-size-fits-all blanket approach, we are bound to increase antimicrobial resistance," he explained.

Antimicrobial Resistance Rising

The recommendation from the Surviving Sepsis Campaign would have everyone on broad-spectrum antibiotics "just in case," he said. "This should give clinicians pause."

Given that the incidence of sepsis is on the rise, broad-spectrum antibiotics should be saved for patients who are sicker on presentation.

"The older, immunocompromised patient who is at greater risk for fungal burden — that's the patient who would draw the most benefit from broad spectrum," he said. For the others, it is important to try to diagnose so that antibiotics administered are appropriate.

If we implement a one-size-fits-all blanket approach, we are bound to increase antimicrobial resistance.

"We should ask ourselves, is this a bad pneumonia or urinary tract infection? And we should look at epidemiology data, which might help us predict the infection," he argued.

"Larger centers usually have an active microbial-surveillance program," which could help determine the source of the infection, and what it likely will not be, Patel said. "Antibiotics resistance patterns vary, not only in a center, but also around the world."

For example, the rate of methicillin-resistant Staphylococcus aureus (MRSA) is 45% in the United States, 17% in Canada, 11% in the United Kingdom, and virtually 0% in the Netherlands, according to Center for Disease Dynamics, Economics, and Policy data cited by Patel and his coauthor, Paul Bergl, MD, also from the Medical College of Wisconsin, in their published counterpoint.

The guidelines are based on data comparisons that do not make a logical argument, he suggested. To evaluate harm, observational studies have looked at two broad groups: those exposed to antibiotics and those not exposed.

The common definition of appropriate antibiotics — "those that drive in vitro activity" — means the comparative group is bound to do worse. This is a non-sequitur and does not follow from the argument posed," Patel explained. "It offers a valid argument, but not a sound argument — which would infer an unsound conclusion."

Comparing appropriate with inappropriate antibiotics is the same as comparing appropriate antibiotics with no antibiotics at all, he and Bergl note.

"We think it's important to tailor antibiotic treatment," Patel told Medscape Medical News. No two patients in the intensive care unit are the same. With a policy that favors broad-spectrum therapy for all, "the opportunity for overtreatment is huge, and that can lead to unintended consequences, including harm."

And if guidelines recommend broad-spectrum antibiotics for all, "of course every patient will want them," he added.

Other Ways to Reduce Antibiotic Use

"We are advocating a thoughtful choice of antibiotics to cover the most likely pathogens," Coz Yataco said. "There will never be a study to compare broad-spectrum antibiotics with no antibiotics; that's not ethically doable," he pointed out.

Every year there are 2.5 million sepsis cases and 270,000 deaths. "We have an aging population with a higher number of chronic diseases and significantly more comorbidities," he reported. "We know that antibiotic overprescribing is a problem, but we should not withhold them from our sickest population."

However, the use of antibiotics in outpatients can be decreased. "That's where a lot of the prescriptions go," he said. And "70% of antibiotics are used in animals for animal production to improve the product," according to a report from the US Food and Drug Administration. That can be reduced.

If we wait for cultures to come back before administering antibiotics, "it could be too late for the patient." Until we have ways to diagnose more accurately, "this is the best course of action," Coz Yataco said.

CHEST 2019: American College of Chest Physicians Annual Meeting. To be presented October 21, 2019.

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