Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis

Abstract

Challenges in the differentiation of the aetiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to significant overuse of antibiotics. Serum procalcitonin, released in response to bacterial infections, but not viral infections, could possibly identify AECOPD requiring antibiotics. In this meta-analysis we assessed the clinical effectiveness of procalcitonin-based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD.Based on a prospectively registered protocol, we reviewed the literature and selected randomised or quasi-randomised trials comparing procalcitonin-based protocols to initiate or discontinue antibiotics versus standard care in AECOPD. We followed Cochrane and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidance to assess risk of bias, quality of evidence and to perform meta-analyses.We included eight trials evaluating 1062 patients with AECOPD. Procalcitonin-based protocols decreased antibiotic prescription (relative risk (RR) 0.56, 95% CI 0.43-0.73) and total antibiotic exposure (mean difference (MD) -3.83, 95% CI (-4.32--3.35)), without affecting clinical outcomes such as rate of treatment failure (RR 0.81, 0.62-1.06), length of hospitalisation (MD -0.76, -1.95-0.43), exacerbation recurrence rate (RR 0.96, 0.69-1.35) or mortality (RR 0.99, 0.58-1.69). However, the quality of the available evidence is low to moderate, because of methodological limitations and small overall study population.Procalcitonin-based protocols appear to be clinically effective; however, confirmatory trials with rigorous methodology are required.

FIGURE 1

Risk of bias graph: authors’ judgements about each risk of bias domain, presented as percentages across all included studies. Attrition bias is low for all short-term outcomes of all included trials.

FIGURE 2

Forest plots depicting the overall effect estimates for each outcome. a) Treatment failure for the index exacerbation, defined as symptoms deterioration, non-improvement, intensive care unit admission or death within 1–4 weeks of recruitment; b) length of hospital stay for the index exacerbation; c) antibiotic exposure for the index exacerbation: proportion of patients who were prescribed antibiotics on admission; d) overall mortality at longest follow-up. Data are presented as n/N, unless otherwise stated. PCT: procalcitonin; M-H: Mantel–Haenszel method; df: degrees of freedom.