Procalcitonin Has Limited Value in Reducing Antibiotic Use
Procalcitonin (PCT) is the precursor peptide of calcitonin which under normal circumstances is secreted by thyroid C-cells in response to hypercalcemia. PCT is normally undetectable in serum (<0.05 ng/mL), but is produced in large quantities by many cells in response to bacterial endotoxins and cytokines such as IL-1, IL-6 and TNF. The association between elevated PCT and bacterial infection was first described in 1993. In contrast, viral infections increase secretion of interferon, which attenuates secretion of PCT.
PCT has been used clinically to distinguish bacterial from viral infections and reduce antimicrobial therapy.The strongest evidence has supported the use of PCT for managing antibiotic therapy in patients with lower respiratory tract infections. A meta-analysis of 8 studies with 3431 patients that was published in 2011indicated that PCT monitoring of patients with lower respiratory tract infections resulted in a 31% decrease in antibiotic prescriptions and a decrease in antibiotic therapy duration of 1.3 days (Li H et al. Antimicrob Agents Chemother 2011;53:379-87).
Surprisingly, the Procalcitonin Antibiotic Consensus Trial (ProACT), which was recently published in the New England Journal of Medicine, came to a different conclusion. ProACT involved 14 urban academic hospitals that enrolled 1656 adult patients who presented to the hospital emergency department and were initially diagnosed with a lower respiratory tract infection. All patients had procalcitonin levels measured by the VIDAS BRAHMS assay but results were shared only with the physicians of the patients randomly assigned to procalcitonin-guided antibiotic prescription. The study used the procalcitonin cutoff values that were approved by the FDA in 2017. Antibiotics were strongly discouraged for procalcitonin levels <0.1, discouraged for levels 0.1 to 0.25, recommended for levels >0.25 to 0.5, and strongly recommended for levels >0.5 μg per liter.
The primary outcome was total antibiotic exposure, defined as the total number of antibiotic-days within 30 days after enrollment. ProACT found no significant difference in antibiotic exposure during the first 30 days between the procalcitonin group and the usual-care group (mean antibiotic-days, 4.2 and 4.3 days). Rapid availability of procalcitonin results had no significant impact on whether or not physicians prescribed antibiotics for patients with suspected lower respiratory tract infections.
The exact reasons why the results of this recent research contrast with previous studies are unclear, but the ProACT investigators found that procalcitonin test results generally matched up with how sick a patient appeared as well as their physician’s judgment on how likely it was they had a bacterial infection. Even when physicians did not know their patient’s procalcitonin result, their decision to prescribe antibiotics was generally the same as when physicians did know the result. Procalcitonin offered no incremental value over clinical judgement.
Reference
Huang DT, et al. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection. New Engl J Med, May 20, 2018, DOI: 10.1056/NEJMoa1802670
