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Procalcitonin-Guided Antibiotic Prescription for Suspected Lower Respiratory Tract Infection; A Randomized Clinical Trial

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A7706 - Procalcitonin-Guided Antibiotic Prescription for Suspected Lower Respiratory Tract Infection; A Randomized Clinical Trial
Author Block: D. T. Huang1, D. M. Yealy2, M. R. Filbin3, A. M. Brown2, C. H. Chang4, Y. Doi5, M. W. Donnino6, J. M. Fine7, M. J. Fine4, M. A. Fischer8, J. M. Holst9, P. C. Hou10, J. A. Kellum11, F. Khan12, M. C. Kurz13, S. Lotfipour14, F. LoVecchio15, O. M. Peck-Palmer16, F. Pike17, H. Prunty2, R. L. Sherwin18, L. Southerland19, T. Terndrup19, L. A. Weissfeld20, J. Yabes4, D. C. Angus11, The ProACT Investigators; 1Critical Care Medicine and Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 2Emergency Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 3Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States, 4Internal Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 5Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, United States, 6Emergency Medicine and Pulmonary/Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States, 7Pulmonary/Critical Care Medicine, Norwalk Hospital, Norwalk, CT, United States, 8Emergency Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, United States, 9Emergency Medicine, Essentia Health, Duluth, MN, United States, 10Emergency Medicine, Brigham and Women's Hospital, Boston, MA, United States, 11Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States, 12Emergency Medicine, University of Maryland, Baltimore, MD, United States, 13Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL, United States, 14Emergency Medicine, University of California at Irvine, Irvine, CA, United States, 15Emergency Medicine, Maricopa Medical Center, Maricopa, AZ, United States, 16Pathology, University of Pittsburgh, Pittsburgh, PA, United States, 17Critical Care Medicine and Emergency Medicine, Eli Lilly and Company, Indianapolis, IN, United States, 18Emergency Medicine, Detroit Receiving Hospital, Detroit, MI, United States, 19Emergency Medicine, The Ohio State University, Columbus, OH, United States, 20Statistics Collaborative, Inc., Washington, DC, United States.
Rationale: The impact of procalcitonin on antibiotic prescription in suspected lower respiratory tract infection (LRTI) is unclear. Methods: In 14 US emergency departments, we randomized patients with an initial primary clinical diagnosis of LRTI whose clinician would consider procalcitonin in antibiotic decision-making to usual care or an intervention consisting of measuring procalcitonin and providing the result, together with an antibiotic prescription guideline based on the result, to the clinician. As per prior trials, the guideline provided graded recommendations to use or not use antibiotics based on four procalcitonin tiers. Exclusion criteria included prior antibiotics, endotracheal intubation, and severe immunosuppression. We conducted training for all hospital clinicians involved in antibiotic prescription for LRTI, and disseminated national antibiotic guidelines to promote best practice in usual care. In the procalcitonin arm, we embedded procalcitonin results into the electronic record, obtained serial procalcitonin levels in hospitalized patients, and conducted audit and feedback of clinician adherence to procalcitonin-guided recommendations. In the usual care arm, we also measured procalcitonin at enrollment, though clinicians were blinded to results. Research staff blinded to arm assessed post-discharge outcomes. The primary hypotheses were that the intervention would impact the number of antibiotic-days but not increase the proportion that experienced adverse outcomes by >4.5% within 30 days. Results: We enrolled 1656 patients (826 procalcitonin-guided antibiotic prescription, 830 usual care), of whom 782 (47.2%) were hospitalized, 603 (36.4%) received antibiotics in the emergency department, and 1045 (63.1%) received antibiotics within 30 days. In the procalcitonin arm, initial procalcitonin results were obtained and reported to the treating clinician in 792 of 826 (95.9%) patients. In both arms, initial antibiotic prescription was more than two-fold higher in patients with initial procalcitonin levels in the highest tier versus the lowest tier. There was no difference in antibiotic exposure during the first 30 days (mean antibiotic-days: 5.0 versus 5.2 days, -0.3 day difference; 95% confidence interval [CI], -0.9 to 0.4 days). By 30 days, 97 patients in the procalcitonin arm (11.7%) versus 109 patients (13.1%) in usual care experienced the combined adverse outcome endpoint (-1.4% difference; 95% CI, -4.6% to 1.8%). Conclusions: Procalcitonin-guided antibiotic prescription for suspected LRTI did not impact antibiotic exposure or adverse outcomes. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986)
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