Procalcitonin assay has little impact on antibiotic prescription for lower respiratory infection
The use of procalcitonin assays had little impact on antibiotic exposure in patients who presented to emergency departments (ED) with suspected lower respiratory tract infections, according to findings of the ProACT* trial presented at the recent sessions of the American Thoracic Society (ATS 2018).
“[I]t seems likely that physicians already commonly withheld antibiotics based 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 judgment,” said study lead author Associate Professor David Huang from the Department of Critical Care Medicine and Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, US.
The study was conducted at 14 hospitals in the US where 1,656 adult patients presenting to the ED with suspected acute lower respiratory tract infections (<28 days) and in whom the need for antibiotics was uncertain were randomized to either usual care (n=830, mean age 53.2 years, 42.7 percent male) or the procalcitonin group (n=826, mean age 52.9 years, 43.2 percent male).
Physicians treating patients in the procalcitonin group were provided with real-time results of procalcitonin assays as well as guidelines on antibiotic use. Blood samples for procalcitonin measurement were obtained at the ED for all patients and again 6–24 hours later and at days 3, 5, and 7 among those hospitalized. Participants in the usual care group also had their blood drawn at the ED for procalcitonin assay but treating physicians were not provided with the results.
Of the total cohort, 47.2 percent of patients required hospitalization and 36.5 and 59.4 percent received antibiotics at the ED and within 30 days of enrolment, respectively. Procalcitonin assay results were available for 95.9 percent of patients in the procalcitonin group and 2.2 percent of patients in the usual care group.
The initial assay revealed that most patients were in the lowest procalcitonin level tier (<0.1 µg/L; 77.4 percent), the tier at which the FDA strongly discourages antibiotic use.
Comparable efficacy and safety outcomes
The number of antibiotic days within 30 days of enrolment was comparable between patients in the procalcitonin and usual care groups (mean, 4.2 vs 4.3 days, difference -0.05 days, 95 percent confidence interval [CI], -0.6 to 0.5; p=0.87). [N Engl J Med 2018;doi:10.1056/NEJMoa1802670; ATS 2018, abstract A7706]
At 30 days, the proportion of patients who experienced adverse outcomes (intensive care unit admission and subsequent visits to the ED) was also similar regardless of whether they had received procalcitonin-guided or usual care (11.7 percent vs 13.1 percent, difference -1.5 percentage points, 95 percent CI, -4.6 to 1.7; p<0.001 for noninferiority).
A secondary analysis revealed that procalcitonin almost halved antibiotic exposure in the ED among patients with acute bronchitis (17.3 percent vs 32.1 percent).
Physicians adhered to the procalcitonin guideline recommendations at all time points in 64.8 percent of patients in the procalcitonin group, with the main causes of deviation from guidelines (antibiotic prescription despite low procalcitonin levels) attributed to “clinician belief that a bacterial infection was present” (39.3 percent) and “clinician belief that the patient had an acute COPD exacerbation requiring antibiotics” (33.9 percent).
One potential reason for the findings was that despite physicians in the usual care group not being privy to procalcitonin assay results, antibiotic prescriptions tended to be less likely among patients with lower procalcitonin tiers. Patients with lower tiers also possibly demonstrated “fewer clinical features of infection” and as such, procalcitonin assay results had little influence on treatment decisions, said the researchers.
Future role of procalcitonin
According to the researchers, the findings from ProACT differed from that of previous studies which showed a lower rate of antibiotic exposure with the use of procalcitonin-guided antibiotic prescriptions in lower respiratory tract infections. [Chest 2007;131:9-19; Lancet 2004;363:600-607; JAMA 2009;302:1059-1066]
“In the decade since the largest previous trial completed enrolment, there has been increased attention to antibiotic overuse and stewardship and movement toward shorter courses of antibiotic treatment based on evidence and guidelines. Such shifts in practice may have resulted in less opportunity for the intervention we examined to further reduce antibiotic exposure,” they said.
“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,” said Huang.