Background Different types of acute exacerbations of COPD (AECOPD) have been described, such as those driven by bacteria, viruses or by enhanced eosinophilic inflammation. Bacterial infections, where antibiotics are indicated, appear to account for approximately half of COPD exacerbations. However, challenges in differentiation of the aetiology of AECOPD have led to significant overuse of antibiotics. Serum procalcitonin, released in response to bacterial but not viral infections or non-specific inflammation, could possibly identify AECOPD requiring antibiotics. In this meta-analysis we assessed safety and clinical effectiveness of procalcitonin-based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD.

Methods Based on a prospectively registered protocol, we systematically reviewed the literature and selected randomised or quasi-randomised controlled trials comparing procalcitonin based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD versus standard care. We followed Cochrane’s and GRADEs guidance to assess risk of bias, quality of evidence and to perform meta-analyses.

Results Eight completed trials evaluating 1,062 patients with AECOPD met the inclusion criteria. Procalcitonin-based protocols used in all included trials were similar. Antibiotics were recommended for procalcitonin levels >0.25 μg/L and discouraged for lower levels. All studies were open-labelled or single blinded and the final decision to administer or withhold antibiotic was left to the responsible clinician, who could deviate from the protocol. Adherence to procalcitonin-based protocols ranged between 61.3% and 98.1%. Procalcitonin-based protocols decreased antibiotic prescription (RR 0.56 [0.43, 0.73]) and the total antibiotic exposure (MD −3.83 [−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 [0.57, 1.70]). However, the quality of the available evidence is low to moderate because of methodological limitations and small overall study population.

Conclusion Procalcitonin-based protocols to guide the administration of antibiotics in patients presenting with AECOPD appear safe and clinically effective. The quality of the available evidence is low-to-moderate because of methodological limitations and small overall population. Thus, additional appropriately designed and powered confirmatory randomised controlled trials are required.