Published in the November 2011 issue of Today’s Hospitalist
THROUGHOUT EUROPE, physicians regularly order blood tests for the biomarker procalcitonin. They use those levels to help them determine whether “and for how long “to use antibiotics to treat patients with bacterial infections.
In North America, however, few physicians think that procalcitonin-guided therapy is ready for prime time. An article in the Aug. 8/22, 2011, Archives of Internal Medicine, however, aims to kick-start its wider adoption.
In that study, authors created algorithms to help physicians make therapy decisions for patients with suspected pneumonia, sepsis or other illnesses commonly treated with antibiotics. Paying attention to procalcitonin levels, the authors contend, can go a long way toward "reducing antibiotic overconsumption … without sacrificing patient safety."
The algorithms are based on the results of 14 randomized controlled trials that included more than 4,400 patients treated in primary care, emergency departments and intensive care units, mostly in Europe. Those studies consistently found that basing antibiotic decisions on procalcitonin levels led to many fewer antibiotics being given to fewer patients without causing any harm, explains lead author Philipp Schuetz, MD, MPH, an endocrinologist and internist at the University of Basel in Switzerland.
"If it works in Europe, why would it not work in the U.S. as well?" he asks. "For pneumonia patients and inpatients, the data are very solid."
Antibiotic stewardship vs. taking risk
Why have procalcitonin algorithms been slow to catch on in the U.S.? Dr. Schuetz cites differences in medical practice. "In Europe, patients and physicians are more worried about the side effects of antibiotics," he says. "In the U.S., physicians are worried about lawsuits and not taking risks." Dr. Schuetz has witnessed that practice difference over the past two years, doing research at Harvard University and Beth Israel Deaconess Medical Center. In the U.S., he points out, most physicians "would rather overtreat 20 patients who may have viral pneumonia to not miss the one in 100 that maybe needs antibiotics. In Europe, there is more of a sense that overtreating can have detrimental effects as well, for patients and society as a whole."
Another barrier, Dr. Schuetz adds, is that nearly all the studies on procalcitonin ” and certainly the largest ones “have been conducted in Europe. Without significant U.S. and Canadian trials published in top North
American journals, American opinion leaders are wary about revising treatment guidelines.
But change may be coming. Many physicians in the U.S. are becoming just as concerned as their European colleagues about finding ways to curb the overuse of antibiotics. Some states, including California, now mandate antimicrobial stewardship programs in hospitals.
Monitoring procalcitonin levels can help, says Dr. Schuetz. He has recently worked with hospitals from California to Florida that now include use of the marker in their sepsis guidelines.
Tailoring individual treatment
Procalcitonin, which is separate from calcitonin, was discovered in the 1980s. Ten years later, researchers found that procalcitonin levels rise in the presence of sepsis, pneumonia or another systemic bacterial infection. In 2007, the FDA approved a serum PCT immunoassay as a prognostic indicator in septic patients.
The first studies on using procalcitonin as a marker of bacterial infections, Dr. Schuetz says, looked at patients walking into emergency departments with respiratory infections. Doctors found that elevated procalcitonin levels allowed them to distinguish between patients who would be helped by antibiotics, such as those with pneumonia, and those who wouldn’t because they had bronchitis, a COPD exacerbation or something else not caused by bacteria.
"If someone comes in with clinical symptoms, in addition to doing the regular blood draw, nurses also obtain a procalcitonin level," Dr. Schuetz explains. (In the U.S., the test costs $25, with results back in about 60 minutes.) "When the patient comes back from X-ray and you are ready to do the overall assessment, you have the marker back."
The marker also helps physicians determine the duration of treatment. "If you have somebody with pneumonia, you always want to treat that patient right away," says Dr. Schuetz, "but the question really is how long do you want to treat." While guidelines say to treat patients between seven and 10 days, "it would make much more sense to be able to make an individualized treatment decision. The guy with a not very good immune system needs 10 days, but the young guy with not very bad pneumonia, maybe four days is enough. Treating everybody for seven days doesn’t make any sense, but there are no good studies of duration."
How to use the marker
With pneumonia patients, Dr. Schuetz now gets a baseline procalcitonin level, starts the patient on antibiotics if warranted and then orders procalcitonin levels every two days.
Normally after three or four days, the patient improves clinically and the marker comes down. When it reaches normal values “often at day five “he will stop the antibiotics. If the marker is not coming down, Dr. Schuetz explains, it may be a signal to give the patient another close look, change drugs or do more diagnostics. If the marker remains very low from the start, that may indicate that the patient doesn’t have pneumonia but a pulmonary embolism, lung tumor or other missed problem presenting like pneumonia.
Studies in ICUs of patients with sepsis also indicate that tracking procalcitonin levels can help physicians decide on antibiotic duration. "In the ICU," he notes, "the idea is that if you can stop early, you can prevent secondary complications."
In the Archives study, Dr. Schuetz and colleagues in Switzerland, Massachusetts and Canada summarize the randomized trials to date in different settings and then propose treatment algorithms for patients in each setting.
"All the studies have shown that there is no harm associated with these algorithms, and antibiotics are reduced by between 30% and 50%, depending on the study," he says. While the data are particularly solid for pneumonia patients, he would like to see another trial in the ICU. "ICU patients are very high-risk," Dr. Schuetz notes. "You don’t want to risk anything for these patients."
In his experience, Dr. Schuetz says, physicians need to use the algorithms a few times before they start trusting them.
"In the beginning, you feel very awkward if you are used to treating a patient with pneumonia for 14 days," he says. However, once physicians see 20 patients improve normally on only five days of antibiotics, "they start to believe and change the way they practice medicine," says Dr. Schuetz. "But it takes a while."
Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.