Meta-analysis of macrolide maintenance therapy for prevention of disease exacerbations in patients with noncystic fibrosis bronchiectasis

Donghai Wang, Wenlong Fu, Jihong Dai, Donghai Wang, Wenlong Fu, Jihong Dai

Abstract

Background: Macrolide maintenance treatment remains controversial for patients with noncystic fibrosis (non-CF) bronchiectasis, we performed a meta-analysis to estimate the benefits and safety of macrolides therapy in adults and children with non-CF bronchiectasis.

Methods: PubMed, Embase, the Cochrane Library, and Web of Science databases were searched for all the randomized controlled trials of macrolides for treating non-CF bronchiectasis. The primary outcome was improvement of bronchiectasis exacerbations. Secondary outcomes included adverse events and macrolide resistance.

Results: A total of 10 studies involving 602 patients were included in the analysis. Pooled results showed that macrolide therapy significantly reduced the number of patients who suffered from exacerbations (RR = 1.56, 95% CI = 1.14-2.14, P = .006, I = 72%), number of patients who experienced at least 3 exacerbations (RR = 0.55, 95% CI = 0.39-0.77, P = .0005, I = 40%), average exacerbations per patient during the observation time (SMD = -0.69, 95% CI = -1.06 to -0.32, P = .0002, I = 60%), and bronchiectasis exacerbation-related admissions (RR = 0.46, 95% CI = 0.23-0.96, P = .04, I = 0%). Specified subgroup analyses of the number of patients free from exacerbations were further performed; macrolide therapy showed a significant benefit in both children (RR 5.03, 95% CI 2.02-12.50, P = .0005, I = 45%) and adults (RR = 1.66, 95% CI = 1.37-2.02, P < .00001, I = 79%); azithromycin showed a significant reduction on the number of patients who suffered from exacerbations (RR = 2.25, 95% CI = 1.67-3.02, P < .00001, I = 0%), was different from erythromycin (RR = 1.33, 95% CI = 0.92-1.94, P = .13, I = 0%) and roxithromycin (RR = 1.14, 95% CI = 0.97-1.35, P = .11, I = 0%). The pooled results also showed no higher risk of adverse events (RR = 0.98, 95% CI = 0.85-1.13, P = .80, I = 8%), even a lower risk of severe adverse events (RR = 0.53, 95% CI = 0.33-0.85, P = .009, I = 0%). However, a higher risk of macrolide resistance (RR = 3.59, 95% CI 2.6-4.96, P < .00001, I = 0%) was observed.

Conclusion: For both children and adults with non-CF bronchiectasis, macrolide maintenance therapy can effectively reduce bronchiectasis exacerbations, especially for patients with more frequent exacerbations and needing hospital treatment. Azithromycin was more effective than other macrolides. Macrolide maintenance therapy did not increase the risk of adverse events, but may increase the risk of macrolide resistance.

Figures

Figure 1
Figure 1
Effects of macrolide therapy on the number of patients with non-CF bronchiectasis free from exacerbations.
Figure 2
Figure 2
Subgroup analysis of effects of macrolide therapy on the number of patients with non-CF bronchiectasis free from exacerbations.
Figure 3
Figure 3
Effects of macrolide therapy on the number of patients who experienced at least 3 exacerbations during the observation time.
Figure 4
Figure 4
Effects of macrolide therapy on the frequency of exacerbations.
Figure 5
Figure 5
Effects of macrolide therapy on bronchiectasis exacerbation-related admissions.
Figure 6
Figure 6
Effects of macrolide therapy on the number of patients suffered from any adverse event.
Figure 7
Figure 7
Effects of macrolide therapy on the number of patients suffered from any severe adverse event.
Figure 8
Figure 8
Effects of macrolide therapy on the macrolide resistance.

References

    1. Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010;65suppl 1:i1–58.
    1. Khoo JK, Venning V, Wong C, et al. Bronchiectasis in the last five years: new developments. J Clin Med 2016;5:115.
    1. Fjaellegaard K, Sin MD, Browatzki A, et al. Antibiotic therapy for stable non-CF bronchiectasis in adults—a systematic review. Chron Respir Dis 2017;14:174–86.
    1. Seitz AE, Olivier KN, Adjemian J, et al. Trends in bronchiectasis among medicare beneficiaries in The United States, 2000–2007. Chest 2012;142:432–9.
    1. Chang AB, Bell SC, Torzillo PJ, et al. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand Thoracic Society of Australia and New Zealand guidelines. Med J Aust 2015;202:130.
    1. McDonnell M, Ward C, Lordan J, et al. Non-cystic fibrosis bronchiectasis. QJM 2013;106:709–15.
    1. Haworth CS, Bilton D, Elborn JS. Long-term macrolide maintenance therapy in non-CF bronchiectasis: evidence and questions. Respir Med 2014;108:1397–408.
    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. J Clin Epidemiol 2009;62:e1–34.
    1. Cymbala AA, Edmonds LC, Bauer MA, et al. The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis. Treat Respir Med 2005;4:117–22.
    1. Koh Y, Lee M, Sun Y, et al. Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Eur Respir J 1997;10:994–9.
    1. Tsang K, Ho PI, Chan K, et al. A pilot study of low-dose erythromycin in bronchiectasis. Eur Respir J 1999;13:361–4.
    1. Liu J, Zhong X, He Z, et al. Effect of low-dose, long-term roxithromycin on airway inflammation and remodeling of stable noncystic fibrosis bronchiectasis. Mediat Inflamm 2014;2014:1–4.
    1. Wong C, Jayaram L, Karalus N, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 2012;380:660–7.
    1. Masekela R, Anderson R, Gongxeka H, et al. Lack of efficacy of an immunomodulatory macrolide in childhood HIV related bronchiectasis: a randomised, placebo-controlled trial. J Antivir Antiretrovir 2013;5:44–9.
    1. Valery PC, Morris PS, Byrnes CA, et al. Long-term azithromycin for indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial. Lancet Resp Med 2013;1:610–20.
    1. Serisier DJ, Martin ML, McGuckin MA, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 2013;309:1260–7.
    1. Altenburg J, de Graaff CS, Stienstra Y, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 2013;309:1251–9.
    1. Diego AD, Milara J, Martinez-Moragón E, et al. Effects of long-term azithromycin therapy on airway oxidative stress markers in noncystic fibrosis bronchiectasis. Respirology 2013;18:1056–62.
    1. Cai Y, Chai D, Wang R, et al. Effectiveness and safety of macrolides in cystic fibrosis patients: a meta-analysis and systematic review. J Antimicrob Chemother 2011;66:968–78.
    1. Yao G-Y, Ma Y-L, Zhang M-Q, et al. Macrolide therapy decreases chronic obstructive pulmonary disease exacerbation: a meta-analysis. Respiration 2013;86:254–60.
    1. Gao Y-H, Guan W-J, Xu G, et al. Macrolide therapy in adults and children with noncystic fibrosis bronchiectasis: a systematic review and meta-analysis. PLoS One 2014;9:e90047.
    1. Fan L-C, Lu H-W, Wei P, et al. Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials. BMC Infect Dis 2015;15:160.
    1. Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012;366:1881–90.
    1. Dumke R, Von Baum H, Lück P, et al. Occurrence of macrolide-resistant Mycoplasma pneumoniae strains in Germany. Clin Microbiol Infect 2010;16:613–6.
    1. Morozumi M, Iwata S, Hasegawa K, et al. Increased macrolide resistance of Mycoplasma pneumoniae in pediatric patients with community-acquired pneumonia. Antimicrob Agents Chemother 2008;52:348–50.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren