Test for Bacteria vs Virus Doesn't Influence Antibiotic Prescribing

David Huang, MD, MPH

Treatment guidelines linked to procalcitonin levels, from an assay approved by the US Food and Drug Administration (FDA) in 2017 to help distinguish bacterial from viral lower respiratory tract infections, did not appear to influence whether antibiotics were prescribed, according to the results of a study of the lab test effect on antibiotic utilization in hospital emergency departments reported at the 2018 American Thoracic Society (ATS) International Conference, San Diego, California, May 18-23.

The findings from the Procalcitonin Consensus Trial (ProACT) were presented by David Huang, MD, MPH, director of the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Administrative Core, and associate professor, Departments of Critical Care Medicine and Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh Pennsylvania. The results were published simultaneously in the New England Journal of Medicine.

Dr. Huang and the ProACT investigators identified a cohort of 1656 patients presenting to emergency medicine departments, at 14 hospitals in the United States which were confirmed to have a high level of adherence to Joint Commission pneumonia core measures. The patients, enrolled in the study between November 2014 and May 2016, had received an initial diagnosis of acute lower respiratory tract infection with notation of uncertainty regarding the need for antibiotics.

The patients were randomized 1:1 to a procalcitonin-guided treatment group or to a treatment-as-usual group. Clinicians for both treatment groups received national antibiotic guidelines for lower respiratory tract infection, and the procalcitonin-linked antibiotic treatment guide, which is based on typically higher procalcitonin peptide levels in bacterial than in viral infections. Levels are reported in 4 tiers, with corresponding guidance for antibiotic treatment ranging from "strongly discouraged" (for procalcitonin levels <0.1µg/liter) to "strongly recommended" (for levels >0.5µg/liter).

For clinicians of the procalcitonin-guided treatment group patients, the investigators took several steps to ensure the test was ordered, the results were received timely, and the implications for treatment were clear, Dr. Huang told Contagion^®.

"We rolled out the PCT (procalcitonin) intervention using quality improvement principles, including extensive use of education, prompts, and feedback, and deployed the intervention in the emergency department and hospital setting, the same setting for which the FDA granted approval for PCT for antibiotic guidance," stated Dr. Huang.

"We also took extra steps to provide outreach to outpatient primary care providers, such as sending letters to providers explaining the study, and for each patient in the PCT intervention arm, providing a letter at discharge with the PCT test result and implications, to be shared with the primary care provider," he said.

The clinicians for the procalcitonin-guided intervention group received assay results for 95.9% of their patients, in a median time of 77 minutes after ordering. In contrast, the level was ordered for 2.2% of patients receiving treatment-as-usual. There was no significant difference between the groups in antibiotic exposure, measured in antibiotic-days by day 30 after the initial visit (mean 4.2 with intervention, mean 4.3 with treatment-as-usual). There was also no significant difference between groups in the percentage of patients receiving any antibiotics within 30 days (57.0% with intervention and 61.8% with treatment-as-usual).

The investigators suspect that there was no apparent effect on antibiotic utilization from consistently applying the procalcitonin assay because prescribing was relatively appropriate without the intervention. The clinicians accurately judged the likelihood of bacterial infection from how the patient presented.

"It is important to note that the FDA approved the use of procalcitonin as an adjunct to clinical decision making, not necessarily to follow the results 'carte blanche', and regardless of other clinical signs and symptoms," Dr. Huang explained to Contagion^®.

"Thus, while it is certainly possible that the lack of benefit was due to clinicians choosing not to follow the procalcitonin guideline, we think it equally plausible that clinicians tended to ignore the guideline mainly in those instances where there were signs and symptoms concerning for infection. In this way, they were arguably using the test as indicated by the FDA," he concluded.