Abstract
Background:Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections.Methods and design:We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that procalcitonin-guidance is non-inferior (i.e., at worst a 7.5% higher combined failure rate) to the management with enforced guidelines, but is associated with a reduced total antibiotic use and length of hospital stay.Discussion:Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections.Trial registration:ISRCTN95122877
Highlights
Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity
We summarized guidelines on the management of community-acquired pneumonia (CAP), acute bronchitis and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on the most recent guidelines by the European Respiratory Society (ERS) and the American Thoracic Society (ATS) supplemented by evidence from recent guidelines and published current concepts [16,17,19,20]
Adrenomedullin precursor levels are elevated in sepsis and CAP, have a similar accuracy to predict death compared to the APACHE II score in critically ill patients and improve the prognostic accuracy of the pneumonia severity index (PSI) in CAP, providing an additional margin of safety [28,29]
Summary
Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. Current criteria for assessing the severity of CAP, such as the pneumonia severity index (PSI) and the CAP severity on presentation to hospital scale (CURB65) are well validated, but have important drawbacks for routine care [3,4,5,6] They only predict mortality in CAP and depend mainly on age, thereby underestimating the diseaserelated morbidity in younger patients. In these trials we circumvented the gold standard dilemma for the etiologic diagnosis of LRTIs by assuming absence of serious bacterial infection in patients recovering without antibiotics [10,11,12,13,14]
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