Biomarker Reduces Length of Antibiotic Treatment

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For hospitalized patients with community-acquired pneumonia (CAP), lower measurements of procalcitonin, a biomarker of infection, can reduce the length of antibiotic treatment by an average of seven days.

The study, which is the first research trial of its kind, appears in the first issue for July 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Beat Mu"ller, M.D., of University Hospital in Basel, Switzerland, and nine associates examined 302 consecutive patients with suspected CAP. They divided the study cohort into 151 control subjects who received antibiotics according to usual practice, and 151 patients who were given antibiotics based on higher or lower levels of procalcitonin in their blood. (Procalcitonin is elevated in bacterial infections.)

Pneumonia, which involves inflammation of the lung caused by bacterial infection, viruses or other organisms, can be fatal, especially in the elderly. In 2003 alone, 63,241 people died from pneumonia in the U.S.

“CAP is also the major infection-related cause of death in developed countries,” said Dr. Mu"ller. “Approximately 10 to 20 percent of hospitalized patients with CAP must be admitted to the intensive care unit, where 20 to 50 percent will ultimately die.”

For bacterial CAP, promptly initiating antibiotic therapy is commonly considered the key to survival, he added, “as a delay of more than 4 hours can be associated with increased mortality.”

Yet, within the two study groups, doctors withheld antibiotics upon admission to the hospital in 15 percent of the procalcitonin group and in 1 percent of the control group.

In more than 70 percent of CAP presumed to be of bacterial origin, the causative microbe could not be identified in the lab. Therefore, the results from bacterial cultures are not considered central to the clinical care of the patient.

At the start of the study, all participants were deemed similar in respect to the pneumonia severity index and clinical, laboratory-related and microbiological characteristics.

By basing antibiotic treatment on individual procalcitonin levels, the investigators reduced the average duration of antibiotic use by 55 percent (to 5 days), in contrast to the 12 days of use associated with the “usual care” patients.

Researchers assessed data on each subject at baseline, at 4, 6 and 8 days, and after six weeks.

It took less than 20 minutes to detect levels of serum procalcitonin in the laboratory and results were routinely available within an hour. Each test cost between $15 and $30.

“Procalcitonin appears to be a more reliable measure for individual tailoring and early discontinuance of antibiotic therapy as compared with the routinely used clinical and other parameters,” said Dr. Mu"ller.

In an editorial on the research in the same issue of the journal, Richard G. Wunderink, M.D., of the Feinberg School of Medicine at Northwestern University in Chicago, noted that procalcitonin does not return to low levels for two weeks in bacteremic patients and is also delayed in severe CAP. “The pattern of procalcitonin therapy response in such patients appears to be more a marker of ongoing inflammation than persistent infection,” Dr. Wunderink wrote.

Although the therapy may reduce the duration of antibiotic treatment by an average of seven days, he noted that 14-day treatment of CAP is no longer standard. “Clinical trials and newer guidelines for management of CAP suggest that shorter courses, 7 days or less, should be used. Therefore, the use of a procalcitonin-guided therapy is unlikely to make a major impact if current guidelines are followed.”

He concluded: “The major implication of this study is to support putting a cap on the duration of antibiotic therapy for CAP, similar to that of ventilator-associated pneumonia. Needless prolongation of the duration of antimicrobial treatment is more likely to select for antibiotic resistance or, even worse, place false hope in a failing regimen if ongoing infection really is the cause. The greatest clinical benefit of procalcitonin-directed therapy still appears to be selection of patients who may not need antibiotics at all or, at least not beta-lactam (penicillin) antibiotics.”

American Thoracic Society (ATS)

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