Does procalcitonin make it easier to choose antibiotics wisely for respiratory infections?

- Kenny Lin, MD, MPH

American Family Physician has supported the Choosing Wisely campaign in several ways since it began in 2012, from maintaining a searchable database of primary care-relevant recommendations, to including tables of best practices in clinical review articles, to publishing an occasional editorial containing suggestions of how to implement it into practice. Although Choosing Wisely remains very much a work in progress, staff at the American Board of Internal Medicine Foundation recently identified a "Top 12" list of recommendations that are successfully reducing overuse in health systems across the United States. Leading the list is appropriate use of antibiotics for patients with upper respiratory tract infections, a topic that has been previously reviewed in this journal.

A more challenging task for family physicians may be deciding which patients with lower respiratory tract infections need antibiotics - distinguishing acute bronchitis from chronic obstructive pulmonary disease exacerbations or community-acquired pneumonia. Although clinical decision tools exist, their usefulness in outpatient settings is limited. A Cochrane for Clinicians in the July 1 issue reviewed the benefits and harms of procalcitonin-guided antibiotic therapy compared with routine care for acute respiratory infections on mortality, treatment failure, duration of antibiotic exposure, and antibiotic-related adverse effects. In a meta-analysis of 26 randomized, controlled trials (n = 6708), patients receiving procalcitonin-guided therapy had lower 30-day all-cause mortality (NNT=71) across all settings, but no difference in primary care settings. Rates of treatment failure were similar. Total duration of antibiotic exposure was 2.4 days lower in the procalcitonin group, corresponding to a lower percentage of patients in the procalcitonin group experiencing antibiotic-related adverse effects (16.3% vs. 22.1% in the control group).

Should this evidence lead clinicians to adopt procalcitonin-guided therapy algorithms to improve antibiotic stewardship for acute respiratory infections? Limitations of the Cochrane review are worth noting: the studies were relatively small (mean 258 participants); most were in Europe rather than in the U.S.; and most were in emergency department rather than primary care settings. After the review's publication, Dr. D.T. Huang and colleagues reported the results of a large (n=1656) RCT in 14 U.S. hospitals that compared procalcitonin-guided antibiotic therapy with usual care for patients with lower respiratory tract infections in the emergency department and on the inpatient service, if applicable (782 patients were subsequently hospitalized). In contrast to the Cochrane review, the investigators found no significant differences between the groups in duration of antibiotic exposure or adverse outcomes. They concluded that the addition of procalcitonin results did not significantly improve antibiotic decision-making or patient outcomes.

A take-home message from the Cochrane review and the recent U.S. trial is that the effects of procalcitonin measurement on diagnosis and management of acute respiratory infections depend on the clinical setting, patient characteristics, and preexisting adherence of clinicians to high-value care guidelines for antibiotic prescribing. This test may be helpful in certain cases, but probably should not be used routinely.