Effect of Procalcitonin-Based Guidelines vs Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections: The ProHOSP Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 302; no. 10; pp. 1059 - 1066
• Main Authors: Schuetz, Philipp, Christ-Crain, Mirjam, Thomann, Robert, Falconnier, Claudine, Wolbers, Marcel, Widmer, Isabelle, Neidert, Stefanie, Fricker, Thomas, Blum, Claudine, Schild, Ursula, Regez, Katharina, Schoenenberger, Ronald, Henzen, Christoph, Bregenzer, Thomas, Hoess, Claus, Krause, Martin, Bucher, Heiner C, Zimmerli, Werner, Mueller, Beat, ProHOSP Study Group, for the
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 09.09.2009
• Subjects: Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Calcitonin - blood; Calcitonin Gene-Related Peptide; Clinical trials; Decision Support Techniques; Drug therapy; Drug Utilization; Emergency Service, Hospital; Female; General aspects; Humans; Length of Stay; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pneumology; Practice Guidelines as Topic; Protein Precursors - blood; Respiratory diseases; Respiratory system : syndromes and miscellaneous diseases; Respiratory Tract Infections - blood; Respiratory Tract Infections - drug therapy; Respiratory Tract Infections - mortality; Risk factors; Side effects; Treatment Outcome; Lung disease; Pneumonia; Respiratory disease; Procalcitonin; Standard; Randomized controlled trial; Standards; Recommendation; Infection; Medicine; Randomization; Medical prescription; Clinical trial; Antibacterial agent; Pneumopathy; Comparative study
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2009.1297

CONTEXT In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs). OBJECTIVE To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes. DESIGN, SETTING, AND PATIENTS A 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. INTERVENTION Patients 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 MEASURES Noninferiority 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. RESULTS The 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%). CONCLUSION In 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 REGISTRATION isrctn.org Identifier: ISRCTN95122877