Elsevier

The Lancet

Volume 363, Issue 9409, 21 February 2004, Pages 600-607
The Lancet

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Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial

https://doi.org/10.1016/S0140-6736(04)15591-8Get rights and content

Summary

Background

Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay.

Methods

243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0·1 μg/L or <0·25 μg/L) or encouraged (≥;0·5 μg/L or ≥0·25 μg/L), respectively. Reevaluation was possible after 6–24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat.

Findings

Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0·49 (95% CI 0·44–0·55; p<0·0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%).

Interpretation

Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.

Published online Feb 10, 2004. http://image.thelancet.com/extras/04art1162web.pdf

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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