Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection

Abstract

Background: The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.

Methods: In 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.

Results: A total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval [CI], -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% [96 patients] and 13.1% [109 patients]; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days.

Conclusions: The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).

Figure 1.. Screening, Randomization, and Follow-up.

A patient could have had more than one reason for exclusion. Mixed modeling was used to impute missing data for the intention-to-treat analysis of the primary outcome. Fifteen patients who were found to be ineligible after enrollment were retained in the intention-to-treat analysis of the primary outcome; the reasons for ineligibility were previous receipt of antibiotics (7 patients), homelessness (2), enrollment in the Procalcitonin Antibiotic Consensus Trial (ProACT) in the past 30 days (1), severe immunosuppression (1), current long-term dialysis (1), metastatic cancer (1), and site logistic issues (2). A total of 27 patients who completed the 30-day follow-up could not recall their use of antibiotics. LAR denotes legally authorized representative.

Figure 2.. Antibiotic-Days by Day 30 after Enrollment.

Violin plots for the primary outcome of antibiotic-days by day 30 are shown. The width of the colored shape indicates the probability density of patients with a given result. The gray notched box plots represent the median (yellow horizontal line), 95% confidence interval of the median (notch), interquartile range (25th to 75th percentile) (box), and the upper 1.5 times the interquartile range (solid vertical line).

Figure 3.. Antibiotic Exposure over Time.

Day 1 is from the time of enrollment to midnight. Day 2 and beyond are from midnight to midnight. Serial procalcitonin levels were obtained from hospitalized patients through day 7. Data on post-discharge antibiotic exposure were derived from the intention-to-treat analysis of the primary outcome.