Fast track — ArticlesEffect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial
Introduction
Lower respiratory tract infections—ie, acute bronchitis, acute exacerbations of chronic obstructive pulmonary disease (COPD) or asthma, and pneumonia—account for almost 10% of the worldwide burden of morbidity and mortality.1 As much as 75% of all antibiotic doses are prescribed for acute respiratory-tract infections, despite their mainly viral cause.1 This inappropriate use of antibiotics is believed to be a main cause of the spread of antibiotic-resistant bacteria.2, 3 Thus, reduction of the excess use of antibiotics is essential to combat the increase of antibiotic-resistant microorganisms.4, 5
To limit antibiotic use, rapid and accurate differentiation of clinically relevant bacterial lower respiratory tract infections from other—mostly viral—causes is pivotal. After obtaining a patient's medical history, physical examination, laboratory tests, and chest radiograph, the clinician is often left with diagnostic uncertainty, because signs and symptoms of bacterial and viral infections widely overlap.6, 7 For example, bacteria can be isolated from sputum in up to 50% of patients with acute exacerbations of COPD, but whether this finding represents colonisation or infection is controversial.8, 9 The absence of specific markers of clinically relevant bacterial infections contributes to the overuse of antibiotics in lower respiratory tract infections, especially in elderly patients with coexisting illnesses.
Circulating amounts of calcitonin precursors, including procalcitonin, are raised in severe bacterial infections, but remain fairly low in viral infections and non-specific inflammatory diseases.10, 11 Findings of many clinical studies have established the superior diagnostic accuracy of procalcitonin in severe infections compared with other markers,12 albeit that the assay used had a limited functional assay sensitivity of 0·3–0·5 μg/L. Since subtle elevations of circulating procalcitonin are not detected, this assay is not accurate for diagnosis of early or localised infections.13, 14, 15 An improved rapid assay with a functional assay sensitivity of 0·06 μg/L has become available.16 We aimed to assess the capability of this sensitive procalcitonin assay to identify bacterial lower respiratory tract infections needing antimicrobial treatment.
Section snippets
Patients
This study was a prospective, cluster-randomised, controlled, single-blinded intervention trial comparing routine use of antimicrobial therapy with procalcitonin-guided antimicrobial treatment for lower respiratory tract infections. We assessed for eligibility patients who presented from Dec 16, 2002, until April 13, 2003, with cough, dyspnoea, or both at the medical emergency department of the University Hospital in Basel, Switzerland—a 784-bed academic tertiary care hospital. The criterion
Results
Of 4119 patients presenting at the emergency department, 597 (14%) had dyspnoea, cough, or both as main symptoms and were screened for the study. Of these, 243 (41%) were eligible and included (figure 1). Baseline characteristics were similar in both treatment groups, overall (table 1) and in a subgroup of 60 patients with acute exacerbations of COPD (table 2). The group classified as others consisted of 24 patients in whom lower respiratory tract infection was diagnosed on admission by the
Discussion
We have shown that procalcitonin guidance substantially and safely reduced antibiotic overuse in patients with lower respiratory tract infections: the risk of antibiotic exposure was reduced by 50%, which equated to 39 fewer antibiotic courses per 100 patients with lower respiratory tract infections. Importantly, withholding antibiotic treatment was safe and did not compromise clinical and laboratory outcome.
Most respiratory-tract infections are due to viral infections.24 Accordingly,
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