Reducing unnecessary antibiotic use in CAP

Testing and treatment are rapidly evolving for inpatients with community-acquired pneumonia.


The hospitalist's approach to community-acquired pneumonia (CAP) is rapidly evolving to include new diagnostic tests and different drugs.

Scott A. Flanders, MD, FACP, gave a rundown of when to use procalcitonin assays and antibiotics during his session on CAP in hospitalized patients at Internal Medicine Meeting 2017.

Identifying CAP etiologies is tricky, Dr. Flanders said. In a 2015 study in the New England Journal of Medicine, 62% of nearly 2,300 adults with CAP requiring hospitalization had no pathogen identified, “even with all the tests the CDC could come up with,” Dr. Flanders explained. About 23% of the patients had only viral pathogens found, and about 11% had only bacterial pathogens.

“I look at this and I realize that, for 90% of our hospitalized patients, we find nothing or a virus. And I ask you, how many of our hospitalized pneumonia patients do we treat with antibiotics? Pretty close to 100%,” said Dr. Flanders, a professor of medicine and director of the hospital medicine program at the University of Michigan Medical School in Ann Arbor.

He explained how biomarkers may help hospitalists determine which CAP patients warrant antimicrobial treatment as opposed to supportive treatment, as well as how to use antibiotics when indicated.

Procalcitonin

Of all the biomarkers for pulmonary infections, procalcitonin has become the most common, Dr. Flanders said. When he asked session attendees how many have the test available, many hands went up in the air. “It's amazing how five years ago, I asked that question, and two hands went up. It has just skyrocketed,” he said.

Procalcitonin levels are higher in patients with bacterial infections, and a quick rise or fall can indicate severity of illness or clinical response, Dr. Flanders explained. Levels are not affected by steroids, and rapid testing is available in many hospitals, he said.

Studies have suggested that procalcitonin may be a useful tool for deciding when to start or continue antimicrobial treatment.

Scott A Flanders MD FACPslashPhoto by Kevin Berne
Scott A. Flanders, MD, FACP/Photo by Kevin Berne.

Most researchers use a cutoff of 0.25 ng/mL to establish the likelihood of a bacterial infection, Dr. Flanders noted. Pooled outcomes from 14 trials suggest that using procalcitonin lowers antibiotic usage and produces similar outcomes for patients, he said.

But there are downsides to consider. “I'm cautious with procalcitonin, and I think you should be too,” Dr. Flanders said. “There are numerous examples of when this fails us, if you will.”

One study of 259 hospitalized CAP patients, published in 2013 by the Journal of Infection, concluded that low procalcitonin level at admission cannot reliably exclude a serious bacterial infection. “The important part of this study was, of the patients they thought were definitely bacterially infected, 23% had an incredibly low procalcitonin,” Dr. Flanders said. On the flip side, about 23% of those with viral infections had elevated procalcitonin levels.

Dr. Flanders emphasized that although procalcitonin is not perfect, it can be a valuable diagnostic tool when used correctly, with serial measurements. “If this is going to safely reduce antibiotic use, you need to follow this on a serial basis,” he said, and it should not be the sole variable used to decide whether to give antibiotics.

If a hospitalist is convinced a patient needs antibiotics, she doesn't need to order a procalcitonin test unless she will serially follow levels to try to reduce treatment duration, Dr. Flanders said, adding that there's no use ordering the test if no antibiotics will be used. “It's most useful when you're sitting on the fence,” he said.

Antibiotics

The need to reduce unnecessary antibiotic use is quite clear.

In 2016, a CDC analysis of more than 300 hospitals showed that 55% of patients hospitalized between 2006 and 2012 received antibiotics. Although use remained stable during that time period, there was a significant shift toward broad-spectrum drugs versus narrow-spectrum drugs.

Many hospitalized patients need broad-spectrum antibiotics, but several studies have estimated that anywhere from 30% to 50% of antimicrobial use in U.S. hospitals is inappropriate, Dr. Flanders said.

“That's a lot of ground to make up,” he said. “When you look at the conditions where we're seeing antibiotic use in U.S. hospitals, pneumonia, urinary tract infections (UTIs), and skin and soft-tissue infections are the big three, and pneumonia is the big daddy of them all,” with more than half of use dedicated to pneumonia and UTIs.

When treating CAP in the hospital, Dr. Flanders suggested using the lowest number and narrowest spectrum of antibiotics and shortening treatment durations if at all possible.

Some patients will benefit from atypical coverage with a macrolide, he noted. For sicker hospitalized patients, especially the ICU population, Dr. Flanders recommends use of a beta-lactam plus a macrolide versus a beta-lactam alone. “A lot of my patients in my hospital don't look so good, so I slant toward the beta-lactam plus the macrolide,” he said.

That said, an increasingly large number of ward patients—especially those in whom Legionella has been considered and is not suspected—may be candidates for beta-lactam monotherapy, Dr. Flanders said. “This may be the patient who gets hospitalized because their COPD is flaring; it's not their pneumonia, per se, or they have heart failure on top of [pneumonia],” he said.

When deciding between fluoroquinolones or a beta-lactam and a macrolide, Dr. Flanders again suggested keeping the patient's condition in mind. “Many hospitalists debate between those. I would say the outcomes are comparable for ward patients. I think beta-lactam plus macrolide seems to be better for the sicker patient populations, but beware of the fluoroquinolones,” he said, noting important downsides such as adverse drug events and declining activity of the broad-spectrum drugs against Pseudomonas and Escherichia coli.

Dr. Flanders said physicians at his institution are moving away from fluoroquinolones, instead preferring beta-lactams/beta-lactamase inhibitors, with azithromycin as their empiric treatment choice.

Some institutions, he said, are choosing to use beta-lactams plus doxycycline, which has some activity against Clostridium difficile. “That may actually be a very reasonable regimen if C. diff in particular is a problem at your institution,” he said. “There will be less outcome data for you to hang your hat on, especially with the doxy-based regimens, but a lot of experienced institutions out there have had good results.”

There are varying thoughts on CAP treatment durations, as well. The 2007 guidelines from the American Thoracic Society and Infectious Diseases Society of America recommend a minimum of five days and suggest that the patient should be afebrile for 48 to 72 hours and have no more than one CAP-associated sign of clinical instability (e.g., heart rate greater than 100 beats/min) before treatment is discontinued. “That was great advice, but it had actually never been studied until this last year, where we got a randomized trial comparing that very approach compared to what the docs usually do,” Dr. Flanders said.

The trial, published in the September 2016 JAMA Internal Medicine, found that five days of treatment versus the doctors' preference (a median of 10 days) produced similar 30-day success rates, and there were fewer 30-day readmissions in the five-day treatment group. In addition, 70% of the intervention group was stable enough to receive five days of treatment, Dr. Flanders noted. “This study suggested it might actually be a better approach than longer durations,” he said.

However, when it comes to stopping therapy, “we don't do this very well,” said Dr. Flanders. Data from his team's ongoing study across 10 Michigan hospitals and 2,500 pneumonia patients showed that about 53% of patients received excess duration of antibiotic treatment. “There's a huge opportunity for us to shorten treatment durations, and I think we need to move more in that direction.”