A new study investigates the effectiveness of measuring procalcitonin levels to gauge the efficacy of antibiotics in treating acute respiratory infections.
Procalcitonin is the precursor of the peptide hormone calcitonin. Calcitonin is produced as procalcitonin primarily by the thyroid gland and reduces the levels of calcium in the blood by inhibiting the activity of osteoclasts, which are involved in the breakdown of bones. Calcitonin also prevents resorption of calcium by the kidneys, further contributing to lower blood calcium levels. In addition to the thyroid, procalcitonin is produced by epithelial cells in response to bacterial infection, and its levels can be correlated with the extent and severity of the infection.
In 2017, the US Food and Drug Administration approved the use of blood procalcitonin levels as a marker of the effectiveness of antibiotics in treating acute respiratory infections and sepsis.1 And while it has been shown that mortality may be reduced by using procalcitonin levels as a guide for antibiotic therapy in intensive care units, conclusive evidence is lacking as many studies lack statistical power. Also, while previous meta-analyses showed that measuring procalcitonin levels reduced antibiotic use, conclusive evidence of its clinical effectiveness was lacking. A new study, which combined data from previous randomized clinical trials, published its findings recently in The Lancet Infectious Diseases.2
The study used data from 26 trials in 12 countries and included a total of 6,708 patients. Of the 26 trials, two trials involved patients with upper respiratory tract infections and lower respiratory tract infections who were receiving treatment in primary care facilities, eleven trials involved patients with lower respiratory tract infection from emergency departments and medical wards, and 13 trials involved patients from intensive care wards who had sepsis because of lower respiratory tract infections. The patients in each of these trials were randomly assigned to one of two groups: those receiving antibiotic treatment based on their blood procalcitonin levels or the control group. The two primary endpoints that were monitored in the two groups were mortality and treatment failure. Apart from these, antibiotic usage, length of stay, and antibiotic side effects were also assessed.
Clinical trial data analysis showed that there were 286 deaths (out of 3,336 patients) in the procalcitonin-guided antibiotic therapy group and 336 deaths (out of 3,372 patients) in the control group. Therefore, mortality was significantly reduced in the procalcitonin group. The effects on mortality were independent of clinical setting or infection type. As for treatment failure, the number of failed cases was less in the procalcitonin-guided group, but the difference between the two groups was statistically insignificant.
Procalcitonin-guided antibiotic treatment reduced the duration of antibiotic exposure to 5.7 days from 8.1 days in the control group, and fewer patients were prescribed antibiotics in the procalcitonin group than in the control group. Furthermore, there was a significant reduction in the side effects associated with antibiotic treatment in the procalcitonin group. However, the duration of hospital stay and intensive care stay were similar in both groups.
A notable limitation of this study was that the value of procalcitonin-guided therapy in primary care settings could not be reliably assessed, as mortality was very low. Additionally, while the procalcitonin-based algorithm, which used procalcitonin cutoff levels to decide the initiation or continuation of antibiotic therapy, was similar across the various trials, adherence to this algorithm varied across trials. Similar results were obtained, however, when data from low adherence and high adherence trials were compared.
The results of this study indicate the beneficial clinical effects of using procalcitonin levels to guide antibiotic therapy in patients with acute respiratory infection. While the cost of using procalcitonin tests as part of a standard treatment regimen is yet to be assessed, its incorporation could significantly improve clinical outcomes and patient care.
Written by Usha B. Nair, Ph.D.
1) US Food and Drug Administration. FDA press release. FDA clears test to help manage antibiotic treatment for lower respiratory tract infections and sepsis. https://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm543160.htm. Updated: Feb 23, 2017. Accessed: Oct 2, 2017.
2) Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, Annane D, Reinhart K, Falsey AR, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Oliveira CF, Maravić-Stojković V, Verduri A, Beghé B, Cao B, Shehabi Y, Jensen JS, Corti C, van Oers JAH, Beishuizen A, Girbes ARJ, de Jong E, Briel M, Mueller B. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2017 Oct 13. pii: S1473-3099(17)30592-3. doi: 10.1016/S1473-3099(17)30592-3. [Epub ahead of print] PubMed PMID: 29037960.