Impact of adherence to procalcitonin antibiotic prescribing guideline recommendations for low procalcitonin levels on antibiotic use
Authors: Malley Brian E. , Yabes Jonathan G. , Gimbel Elizabeth , Chang Chung-Chou H. , Yealy Donald M. , Fine Michael J. , Angus Derek C. , Huang David T. ,   for the ProACT Investigators, Doi Yohei , Eaton Tammy L. , Fine Michael J. , Gimbel Elizabeth A. , Peck Palmer Octavia M. , Pike Francis , Ryman Ashley M. , Weissfeld Lisa A. , Wofford Kourtney A. , Xu Tianyuan , Yabes Jonathan G. , Donnino Michael W. , Aisiku Imoigele P. , Hou Peter C. , Seethala Raghu R. , Sherwin Robert L. , Holst John M. , Fischer Michelle A. , Rafferty Colleen M. , Dachman William D. , LoVecchio Frank , Filbin Michael R. , Mansour Michael K. , Fine Jonathan M. , Hammel Jean M. , Exline Matthew J. , Southerland Lauren T. , Terndrup Thomas E. , Kurz Michael C. , McCullum David L. , Wang Henry E. , Amin Alpesh N. , Lotfipour Shahram , Khan Feras H. , Gentry Wilkerson R. , Prunty Heather A. , Suffoletto Brian , Brown Aaron M. , Jovin Franziska F. 
Published: January 2023

Abstract
Background
The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.

Methods
This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.

Results
Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.

Conclusions
High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction.
Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.