Chest
Volume 131, Issue 1, January 2007, Pages 9-19
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Original Research: COPD
Antibiotic Treatment of Exacerbations of COPD: A Randomized, Controlled Trial Comparing Procalcitonin-Guidance With Standard Therapy

https://doi.org/10.1378/chest.06-1500Get rights and content

Abstract

Background:Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin guidance compared to standard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD.

Methods:A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were randomized at the index exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels; standard-therapy patients received antibiotics according to the attending physician. The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months. Secondary outcomes were clinical recovery, symptom scores, length of hospitalization, ICU stay, death, lung function, exacerbation rate, and time to next exacerbation.

Results:At the index exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%, respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy. Moreover, procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76; 95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV1at 14 days and 6 months did not differ between groups. Within 6 months, the exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21 vs 0.24, respectively), and mean (± SD) time to the next exacerbation (70.0 ± 46.1 vs 70.4 ± 51.9 days, respectively; p = 0.523) were similar in both groups.

Conclusions:Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3.

Section snippets

Patients

From November 2003 to March 2005, consecutive patients ≥ 40 years of age who had been admitted to the emergency department of the University Hospital Basel (Basel, Switzerland) with an ECOPD and met post-bronchodilator therapy spirometric criteria, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines,34within 48 h of emergency department admission were included in this study. An ECOPD was defined as “a sustained worsening of the patient's condition, from the stable

Study Population

From November 2003 to March 2005, 288 patients with suspected COPD exacerbations were admitted to the emergency department (Fig 1). Of the 226 randomly assigned patients, 18 were removed because they failed to meet spirometric criteria for the presence of COPD. No patient dropped out thereafter, and no patient was lost to follow-up.

Baseline characteristics of the patients in both groups were much the same (Table 1). Current use of antibiotic therapy for exacerbations of COPD was reported by 45

Discussion

Our findings indicate that guidance with the measurement of procalcitonin levels reduces the exposure of patients to antibiotics after presentation to the emergency department for exacerbations of COPD. This initial difference in antibiotic exposure is not followed by increased antimicrobial usage after hospitalization for up to 6 months. Thereby, the clinical outcome, including exacerbation rate and time to the next exacerbation, was not compromised. The absolute risk reduction of 31.5% in

Acknowledgments

We are indebted to the patients who participated in this study; to the family physicians for providing follow-up information; to Anja Meyer, Sabina Iannucci, Astrid Vögelin, and Lydia Meier for their most helpful assistance in data collection; to the lung function laboratory staff (Margherita Leo, Germaine Lüdin, Gordana Novicic, Jessica Gebhard, and Diana Wissler); to Fausta Chiaverio for overseeing the laboratory assays; and to Andy Schötzau for statistical advice.

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    This study was funded by the Clinic of Pulmonary Medicine; the Clinic of Endocrinology, Diabetes and Clinical Nutrition; and the Emergency Department of the University Hospital Basel. BRAHMS provided procalcitonin assays for this investigator-driven study. Dr. Beat Müller has served as consultant and received payments from BRAHMS (the manufacturer of procalcitonin assays) to attend meetings and for travel expenses, speaking engagements, or research. The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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