Antibiotic Treatment of Severe Exacerbations of Chronic Obstructive Pulmonary Disease with Procalcitonin: A Randomized Noninferiority Trial

Abstract

BackgroundThe duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.Methods and FindingsWe investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], −7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.ConclusionsAlthough the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).Trial RegistrationClinicalTrials.gov NCT01125098

Serum Procalcitonin as a Biomarker for the Prediction of Bacterial Exacerbation and Mortality in Severe COPD Exacerbations Requiring Mechanical Ventilation

“…Nseir et al [44] reported that PCT >0.5 ng/ml with a positive Gram stain for endotracheal aspirate was associated with bacterial exacerbations. In a multicenter randomized controlled study from Italy, the authors compared 10 days of antibiotic treatment with discontinuation of antibiotics within 3 days plus PCT guidance in patients hospitalized for COPDE [20]. It was found that discontinuing antibiotics on day 3 with PCT <0.25 ng/ml was a safe method, and there was no difference between the groups for outcomes such as exacerbation rate, hospital/ICU admission functional status decline, and mortality within a 6-month period.…”

“…First, it was performed on severe COPDE patients who required ICU admission. Most PCT studies in the literature evaluated prognosis mostly in mild-to-moderate COPDE either in the emergency room or the hospital ward [17,19,20]. Second, the study included patients with severe COPD, mostly GOLD stages III and IV.…”

“…It is accepted as a ‘bacterial infection' biomarker in many systemic infections, including lower respiratory tract infections and COPDE [14,15,16,17,18]. Recently, PCT has been used to guide antibiotic therapy, and it can be safely used to reduce inappropriate antibiotic prescription in COPDE [17,19,20]. However, there are limited data on PCT-guided antibiotic therapy in more severe COPDE cases that require mechanical ventilation and intensive care unit (ICU) admission [21,22].…”

Procalcitonin-guided antibiotic therapy: a potentially effective and efficient strategy

“…The authors did not report any difference in the length of stay in ICU between groups, as well as no difference in mortality and adverse events [7]. In a recent study that we conducted in patients admitted to hospital for severe exacerbations of COPD associated with clinical signs of bacterial infections (increased and purulent sputum and/or respiratory failure), the PCT-guided reduction of duration of antibiotic treatment from 3 to 10 days was not associated with increased risk of exacerbations in the following 6 months [8].…”

Is Procalcitonin Really Useful for Diagnosis and Prognosis of COPD Exacerbations Requiring Mechanical Ventilation?

“…Recently, the clearance of serum PCT has been shown to be useful in driving the duration of antibiotic therapy in patients affected by pneumonia [1] or COPD exacerbation (COPDE) [2,3] , but these latter findings require further confirmation. Finally, the role of PCT in diagnosis and prognosis among critically infectious patients is still controversial.…”