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

Alexander G Mathioudakis, Victoria Chatzimavridou-Grigoriadou, Alexandru Corlateanu, Jørgen Vestbo, Alexander G Mathioudakis, Victoria Chatzimavridou-Grigoriadou, Alexandru Corlateanu, Jørgen Vestbo

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.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside this article at err.ersjournals.com

Copyright ©ERS 2017.

Figures

FIGURE 1
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
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.

References

    1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3: e442.
    1. Wedzicha JA, Wilkinson T. Impact of chronic obstructive pulmonary disease exacerbations on patients and payers. Proc Am Thorac Soc 2006; 3: 218–221.
    1. Bafadhel M, McKenna S, Terry S, et al. . Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 2011; 184: 662–671.
    1. Vestbo J, Hurd SS, Agustí AG, et al. . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187: 347–365.
    1. López-Campos JL, Hartl S, Pozo-Rodriguez F, et al. . Antibiotic prescription for COPD exacerbations admitted to hospital: European COPD audit. PloS One 2015; 10: e0124374.
    1. Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Safety 2014; 5: 229–241.
    1. Biju PG, Garg S, Wang W, et al. . Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice. Shock 2012; 38: 170–176.
    1. van der Does Y, Rood PP, Haagsma JA, et al. . Procalcitonin-guided therapy for the initiation of antibiotics in the ED: a systematic review. Am J Emerg Med 2016; 34: 1286–1293.
    1. de Jong E, van Oers JA, Beishuizen A, et al. . Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16: 819–827.
    1. Schuetz P, Müller B, Christ-Crain M, et al. . Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Evid Based Child Health 2013; 8: 1297–1371.
    1. Schuetz P, Muller B, Christ-Crain M, et al. . Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9: CD007498.
    1. Desai H, Eschberger K, Wrona C, et al. . Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014; 11: 303–309.
    1. Stolz D, Christ-Crain M, Bingisser R, et al. . Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007; 131: 9–19.
    1. Verduri A, Luppi F, D'Amico R, et al. . Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: a randomized noninferiority trial. PloS One 2015; 10: e0118241.
    1. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, et al. . Serum procalcitonin to guide antibiotic treatment in acute exacerbations of chronic obstructive pulmonary disease. PROSPERO 2016: CRD42016036938.
    1. Liberati A, Altman DG, Tetzlaff J, et al. . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009; 151: W65–W94.
    1. Higgins JPT, Altman DG, Sterne JAC. Assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. London, The Cochrane Collaboration, 2011.
    1. Balshem H, Helfand M, Schünemann HJ, et al. . GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011; 64: 401–406.
    1. Corti C, Fally M, Fabricius-Bjerre A, et al. . Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD. Int J Chron Obstruct Pulmon Dis 2016; 11: 1381–1389.
    1. Liu SS, Zhang YB. The value of serum procalcitonin level in guiding the use of antibiotic in patients with acute exacerbation of chronic obstructive pulmonary disease. Chinese J Antibiot 2015; 40: 459–463.
    1. Nangia V, Gandhi K. Use of procalcitonin to guide the antibiotic therapy in patients with an acute exacerbation of COPD in a resource-limited setting: a case-control study. Clin Microbiol Infect 2012; 18: Suppl. 3 O404.
    1. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. . Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004; 363: 600–607.
    1. Kristoffersen KB, Søgaard OS, Wejse C, et al. . Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission – a randomized trial. Clin Microbiol Infect 2009; 15: 481–487.
    1. Schuetz P, Christ-Crain M, Thomann R, et al. . Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302: 1059–1066.
    1. Fan VS, Gharib SA, Martin TR, et al. . COPD disease severity and innate immune response to pathogen-associated molecular patterns. Int J Chron Obstruct Pulmon Dis 2016; 11: 467–477.
    1. Aaron SD, Vandemheen KL, Hebert P, et al. . Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003; 348: 2618–2625.
    1. Niewoehner DE, Erbland ML, Deupree RH, et al. . Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999; 340: 1941–1947.
    1. Agusti A, Bel E, Thomas M, et al. . Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J 2016; 47: 410–419.
    1. Daniels JM, Snijders D, de Graaff CS, et al. . Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 181: 150–157.
    1. Saint S, Bent S, Vittinghoff E, et al. . Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta-analysis. JAMA 1995; 273: 957–960.
    1. Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, et al. . Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006; 19: CD004403.
    1. Schroeck JL, Ruh CA, Sellick JA Jr, et al. . Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother 2015; 59: 3848–3852.
    1. Wutzke SE, Artist MA, Kehoe LA, et al. . Evaluation of a national programme to reduce inappropriate use of antibiotics for upper respiratory tract infections: effects on consumer awareness, beliefs, attitudes and behaviour in Australia. Health Promot Int 2007; 22: 53–64.
    1. Falsey AR, Becker KL, Swinburne AJ, et al. . Utility of serum procalcitonin values in patients with acute exacerbations of chronic obstructive pulmonary disease: a cautionary note. Int J Chron Obstruct Pulmon Dis 2012; 7: 127–135.
    1. Chang CH, Tsao KC, Hu HC, et al. . Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits. Int J Chron Obstruct Pulmon Dis 2015; 10: 767–774.
    1. Bafadhel M, Haldar K, Barker B, et al. . Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function. Int J Chron Obstruct Pulmon Dis 2015; 10: 1075–1083.
    1. Shimizu K, Yoshii Y, Morozumi M, et al. . Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods. Int J Chron Obstruct Pulmon Dis 2015; 10: 2009–2016.
    1. Wang JX, Zhang SM, Li XH, et al. . Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial. Int J Infect Dis 2016; 48: 40–45.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner