• Philipp Schuetz, Mirjam Christ-Crain, Robert Thomann, Claudine Falconnier, Marcel Wolbers, Isabelle Widmer, Stefanie Neidert, Thomas Fricker, Claudine Blum, Ursula Schild, Katharina Regez, Ronald Schoenenberger, Christoph Henzen, Thomas Bregenzer, Claus Hoess, Martin Krause, Heiner C Bucher, Werner Zimmerli, Beat Mueller, and ProHOSP Study Group.
• Department of Internal Medicine, Kantonsspital Aarau, Tellstrasse, CH-5001 Aarau, Switzerland.
• JAMA. 2009 Sep 9;302(10):1059-66.

ContextIn previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).ObjectiveTo examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.Design, Setting, And PatientsA multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.InterventionPatients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.Main Outcome MeasuresNoninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.ResultsThe rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).ConclusionIn patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.Trial Registrationisrctn.org Identifier: ISRCTN95122877.

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