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Procalcitonin-based guidance fails to significantly reduce antibiotic use
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Results of the multicenter, randomized controlled ProACT trial showed that procalcitonin-based guidance did not have a significant impact on antibiotic use compared with standard care among patients who presented to an ED for suspected lower respiratory tract infections.
The findings contradict those of previous studies assessing the value of procalcitonin, a biomarker in the blood that can distinguish between bacterial and viral infections, according to David Huang, MD, MPH, associate professor in the department of critical care medicine and emergency medicine at University of Pittsburgh, Pitt Health Sciences, and colleagues.
“These trials showed that procalcitonin-based guidance reduced the use of antibiotics with no apparent harm, and in February 2017, on the basis of a meta-analysis of these and other trials, the FDA approved a procalcitonin assay to help guide the starting or stopping of antibiotic treatment in suspected lower respiratory tract infection in the ED or hospital,” the researchers wrote in The New England Journal of Medicine. “However, the applicability of these data to routine practice is unclear.”
Huang, who is also director of Pitt’s Multidisciplinary Acute Care Research Organization Center and the Clinical Research, Investigation and Systems Modeling of Acute Illness Center’s administrative core, and colleagues randomly assigned 1,656 patients with suspected lower respiratory tract infections at 14 hospitals in the United States to receive care that was based on rapid procalcitonin assay results and interpretation guidance for clinicians (n = 826) or usual care (n = 830). The procalcitonin assays (VIDAS B.R.A.H.M.S PCT) as well as laboratory training were provided by the manufacturer, bioMérieux Inc. The primary outcome was the difference in antibiotic days between the two groups within 30 days of patient enrollment.
Clinicians obtained procalcitonin assay results for 95.9% of patients receiving procalcitonin-based care and 2.2% receiving usual care. In the procalcitonin group, clinicians adhered to all interpretation guidance 64.8% of the time.
Within 30 days, there were 4.2 antibiotic days in the procalcitonin group and 4.3 antibiotic days in the usual-care group, yielding a difference of –0.05 (95% CI, –0.6 to 0.5). The proportion of patients with adverse events was similar, with 11% experiencing an adverse event in the procalcitonin group and 13.1% experiencing an event in the usual-care group (difference, –1.5%; 95% CI, –4.6 to 1.7).
When examining secondary outcomes, Huang and colleagues found that antibiotic use was lower among patients with acute bronchitis who received procalcitonin-based care vs. usual care (17.3% vs. 32.1%). However, they noted that it was “exploratory” analysis.
The researchers said there are several possible reasons why procalcitonin-based guidance did not significantly reduce antibiotic use. They reported that clinicians providing usual care did not often prescribe antibiotics to patients with lower procalcitonin levels. These patients, they added, had fewer clinical symptoms of infection.
“In other words, it seems likely that physicians already commonly withheld antibiotics on clinical signs alone, and, therefore, instead of the magic bullet I and many others hoped procalcitonin might be, it offered only limited incremental value over clinical judgement,” Huang said in a press release. “I hope our results will help physicians decide when to order procalcitonin and will encourage future research and randomized trials to determine the clinical utility of other novel biomarkers and diagnostic tests in general.” – by Stephanie Viguers
Disclosures: Huang reports receiving nonfinancial support from bioMérieux during the study, as well as grants from ThermoFisher for research outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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These results were surprising. A recent meta-analysis (Schuetz and colleagues) suggested that procalcitonin use in suspected lower respiratory tract infection is associated with reduced antimicrobial use and mortality. Despite a rapid turnaround time on testing and relatively high protocol adherence (> 60%) compared with some other studies, Huang and colleagues were unable to show any difference in antibiotic use or other secondary outcomes in this well-designed study. This study needs to be analyzed within the larger body of procalcitonin literature to determine which subsets of patients should be targeted for testing and what protocols should be used.
There is still strong evidence to suggest that procalcitonin has a role in the hospital setting. A large multicenter ICU study conducted in the Netherlands (de Jong and colleagues) showed that following a daily procalcitonin-based algorithm was associated with a significant reduction in antibiotic use and mortality. Unlike the ProACT study, patients in this study did not just have respiratory illnesses; and they also required longer courses of antibiotics and had daily measurements of procalcitonin. This may partly explain why a benefit was seen. However, a large retrospective study looking at over 20,000 “real world” ICU patients in the U.S. (Chu and colleagues) found that most patients did not have daily procalcitonin measurements and no benefit was seen. This suggests that strict adherence to a daily procalcitonin algorithm in the ICU may be what is important. It should also be noted that ICU trials often use a higher cut-off value of 0.5 µg/L to exclude infection. It is possible the 0.1-0.25 threshold used in this study, although consistent with FDA guidelines, was too low to exclude infection in many cases. Finally, in this study patients were selected when physicians had not yet decided whether to start antibiotics and did not include patients who were already started on antibiotics. It may be that procalcitonin is more useful in the patients who look like they definitely require antibiotics up front (such as in patients with sepsis), but those antibiotics can be discontinued more quickly than clinical judgment alone would allow.
References:
Chu DC, et al. Clin Infect Dis. 2017;doi:10.1093/cid/cix179.
de Jong E, et al. Lancet Infect Dis. 2016;doi:10.1016/S1473-3099(16)00053-0.
Schuetz P, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30592-3.
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