Published in the May 2013 issue of Today’s Hospitalist
WHEN IT COMES TO WAYS to steer clear of unnecessary antibiotics, many experts have suggested that a practice common throughout Europe might be helpful: using serum procalcitonin levels to determine if a patient has a bacterial lower respiratory tract infection that could respond to antibiotics.
It was only in the 1990s that procalcitonin levels were found to rise in the presence of bacterial infection like sepsis or pneumonia. (The levels do not increase with viral infections.) Once an infection is under control, procalcitonin levels have been shown to decrease.
In 2007, the FDA approved a serum procalcitonin assay as a prognostic indicator in septic patients in ICUs. But the test is not approved in the U.S. for treating respiratory tract infections, in part because no studies clearly correlate procalcitonin with bacterial respiratory tract disease. That means its use remains an off-label test for pneumonia care in U.S. hospitals.
A study published in the February 2013 issue of the Journal of Hospital Medicine, however, adds a little more evidence in favor of measuring procalcitonin levels in some suspected pneumonia patients.
The article’s lead author stresses that the study does not address the FDA’s main concerns about the accuracy of procalcitonin levels as a marker of bacterial infection or the safety of using the test to guide treatment. But Edward E. Walsh, MD, head of the infectious disease unit at Rochester General Hospital in Rochester, N.Y., explains that the research does show that elevated procalcitonin levels may very well help clinicians diagnose radiographic pneumonia when chest X-rays are inconclusive.
“What we were looking to see was if doing a procalcitonin would push you one way or the other” in deciding whether a patient has radiographic (and thus bacterial) pneumonia and should benefit from antibiotics using current pneumonia treatment guidelines, Dr. Walsh says. “It looks from our study that a high procalcitonin in somebody with an equivocal chest film could very well be a useful piece of information.”
A top-notch consult
Dr. Walsh’s study specifically implies that the lab test may be comparable to a consult on an uncertain patient from an experienced pulmonologist. That kind of consult can be hard to come by on a timely basis in many hospitals.
Researchers at Rochester General Hospital found that patients who had elevated procalcitonin levels were the same patients who an experienced pulmonologist doing a thorough exam concluded had pneumonia. Patients who did not have higher levels were the same ones the pulmonologist decided didn’t have pneumonia. Think of it this way: When someone comes to the ED with suspected pneumonia and a chest X-ray is ordered, “we find that the radiologist’s reading about 40% of the time notes that the patient definitely doesn’t have an infiltrate or acute disease,” says Dr. Walsh. In a smaller percentage of cases, the radiologist concludes the X-ray definitely shows an infiltrate and there is pneumonia.
But in about one-third of all cases, he explains, the radiologists “basically say, ‘We don’t know what it is. It could be atelectasis, pneumonia, a little bit of edema from heart failure or old scars. We just can’t really tell.’ ”
The Rochester researchers discovered that procalcitonin levels were well-correlated with the two “definite” groups: When the radiologist said there was definitely pneumonia, procalcitonin levels were generally above 0.25 ng/ml (the level used in Europe). And when they noted that the X-ray definitely ruled out pneumonia, median procalcitonin levels were “significantly lower.”
Reaching a more definite conclusion
But what about the group in the middle? Could procalcitonin levels help clinicians come to more definite conclusions about patients with inconclusive X-rays? To try to answer that question, the researchers asked a top-notch pulmonologist to consult in real time on each patient with an ambiguous X-ray.
“He would talk to and examine the patients, look at their white blood cell count, listen to their lungs, and look at their X-rays without the radiologist. And based on his clinical judgment, he would decide what the X-ray showed,” Dr. Walsh explains. “Not too surprisingly, the pulmonologist tended to call these X-rays one way or the other. He didn’t equivocate in most cases.”
Months later, when the researchers sent blood from those patients to a lab at another hospital for procalcitonin level evaluations, they found that the levels tracked pretty closely to the pulmonologist’s conclusions.
In a certain sense, Dr. Walsh says, the study showed that “procalcitonin was a cheap pulmonary consult.” In those cases with an indeterminate X-ray and normal procalcitonin, the exam and evaluation of a very good pulmonologist concluded that the patient probably didn’t have pneumonia. But most of the time that the procalcitonin was elevated, “the pulmonologist said ‘this patient has pneumonia.’ ”
Unanswered questions
The study was not, however, designed to determine or shed any light on whether knowing this information affected which patients received antibiotics or whether the drug choice and duration made a difference to patient outcomes. Following clinical practice guidelines that advocate for early administration of antibiotics for possible pneumonia, Dr. Walsh says that more than 90% of patients in the study received antibiotics, regardless of whether they had pneumonia or not.
That means that the study wasn’t able to answer many of the FDA’s concerns about the safety of using procalcitonin to guide pneumonia treatment. And there are still persistent questions about which groups of patients procalcitonin levels specifically work or don’t work for, such as those with COPD exacerbations or acute bronchitis that results in hospitalization.
Dr. Walsh notes that his group is currently working on a large study to see if procalcitonin levels correlate with definitive bacterial infection. (This current paper was an offshoot of that larger work.)
But study results probably will not affect the unavailability of the lab test at most hospitals. At Rochester General Hospital, Dr. Walsh says, procalcitonin levels cannot be ordered for this purpose and are still done only for patients with sepsis in intensive care.
What this study does show, however, is that procalcitonin levels could help clinicians feel more confident when deciding how to treat a patient with an inconclusive chest X-ray.
“If you are seeing a patient in the emergency room or hospital who has a definitely clear chest film,” he says, “that patient probably doesn’t have a bacterial pneumonia.” On the other hand, “if you have a definite infiltrate on the X-ray, you will give that person antibiotics right away.”
But with the big, nebulous group “this 35% or so who have a vague result on the X-ray “”the procalcitonin might help you decide that you don’t need to give that patient antibiotics.”
Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.
