The outcomes of a national randomized clinical trial show that providing physicians with procalcitonin test results did not reduce antibiotic use in patients with suspected lower respiratory tract infections, a team of US researchers reported this week in the New England Journal of Medicine.
The findings are likely to be viewed as disappointing for those who had hoped that procalcitonin levels could be a reliable biomarker for reducing unnecessary antibiotic use in patients with lower respiratory tract infections, a condition for which antibiotics are often overprescribed. Previous clinical trials in Europe have reported that antibiotic use was reduced by as much as 50% when procalcitonin tests were used to aid clinical decision-making.
Procalcitonin is a protein associated with the body's response to a bacterial infection. Elevated levels of procalcitonin in the blood indicate a bacterial infection, with high levels suggesting a more serious infection such as sepsis. Procalcitonin levels fall with successful treatment of the infection.
In February 2017, the US Food and Drug Administration (FDA) approved the use of a rapid procalcitonin test to help clinicians determine if antibiotics should be started or stopped in patients with lower respiratory tract infections, such as community-acquired pneumonia. The test, which can provide results in as little as 20 minutes, is meant to be used as an adjunct to clinical judgement and traditional diagnostic parameters.
No difference in antibiotic exposure
To assess whether a procalcitonin antibiotic prescribing guideline could reduce exposure to antibiotics without a significantly higher rate of adverse events, researchers at 14 US academic hospitals enrolled 1,656 patients with acute lower respiratory tract infections in the Procalcitonin Antibiotic Consensus Trial (ProACT). The patients, who had been diagnosed in emergency department but had not yet received antibiotics, were randomized 1:1 into two treatment groups.
In one group, clinicians received rapid procalcitonin assay results and an antibiotic-use guideline with recommendations based on four tiers of procalcitonin levels to aid treatment decisions. In the usual-care group, blood was drawn from patients for procalcitonin measurement, but the results were not made available.
The primary outcomes of the study were total antibiotic exposure and adverse outcomes. The researchers hypothesized that within 30 days after enrollment, the total number of antibiotic-days would be lower in the procalcitonin group than in the usual-care group, and adverse outcomes would not be more than 4.5% higher.
But that's not what they found. Overall, 984 patients (59.4%) received antibiotics within 30 days. Among the 826 patients in the procalcitonin group and the 830 patients in the usual-care group, there was no significant difference in antibiotic exposure (4.2 and 4.3 mean antibiotic-days, respectively).
In an analysis of secondary outcomes, there was no significant difference between the procalcitonin and usual-care groups in the percentage of patients receiving any antibiotics within 30 days (57% and 61.8%), the percentage of patients receiving an antibiotic prescription in the emergency department (34.1% and 38.7%), or the mean hospital antibiotic-days among hospitalized patients (2.6 and 2.7 days). The percentage of patients with adverse outcomes (mainly hospital readmission) was also similar in both arms (11.7% and 13.1%).
Only among patients with acute bronchitis was a difference noted, with 17.3% of patients in the procalcitonin group receiving antibiotics, compared with 32.1% in the usual-care group.
Little impact on clinical decision-making
The authors of the study, which is being presented this week at the annual conference of the American Thoracic Society, listed a few possible explanations for the findings. One is that procalcitonin levels generally matched patient symptoms and the clinicians' judgment on whether there was a bacterial infection. In both treatment arms, patients with lower procalcitonin levels were less likely to receive antibiotics than patients with higher levels. Even when clinicians didn't have test results, they prescribed antibiotics at the same rates as those that did.
That suggests that the procalcitonin test results didn't have much of an impact on the clinical decision to withhold antibiotics, perhaps because clinicians had decided to withhold antibiotics based on clinical signs.
The authors also suggest that, with the increased attention to antibiotic overuse and stewardship that has emerged in recent years, procalcitonin tests may not substantially reduce antibiotic prescribing any further.
Lead author David Huang, MD, MPH, a professor and emergency medicine specialist at the University of Pittsburgh School of Medicine, told CIDRAP News that, as a physician who is concerned about antibiotic overuse, he finds the results of the trial disappointing. But he also notes that the study reinforces the idea that, like antibiotics, diagnostic tests should also be used judiciously.
"I think our results are consistent with the overall idea behind the Choosing Wisely campaign: that clinicians should be thoughtful when deciding whether or not to order a diagnostic test," Huang said. "Particularly regarding what value the test truly has and how the test will, or will not, change management."
See also:
May 20 N Engl J Med study
