Abstract：Objective To systematically evaluate the clinical effect of azithromycin (AZM) adjuvant therapy in children with bronchiolitis. Methods Related databases were searched for randomized controlled trials (RCTs) on AZM adjuvant therapy in children with bronchiolitis published up to February 17, 2019. RevMan 5.3 was used to perform the Meta analysis. Results A total of 14 RCTs were included, with 667 children in the intervention group and 651 in the control group. The pooled effect size showed that in the children with bronchiolitis, AZM adjuvant therapy did not shorten the length of hospital stay (MD=-0.29, 95%CI:-0.62 to 0.04, P=0.08) or oxygen supply time (MD=-0.33, 95%CI:-0.73 to 0.07, P=0.10), while it significantly shortened the time to the relief of wheezing (MD=-1.00, 95%CI:-1.72 to -0.28, P=0.007) and cough (MD=-0.48, 95%CI:-0.67 to -0.29, P < 0.00001). The analysis of bacterial colonization revealed that AZM therapy significantly reduced the detection rates of Streptococcus pneumoniae (OR=0.24, 95%CI:0.11-0.54, P=0.0006), Haemophilus (OR=0.28, 95%CI:0.14-0.55, P=0.0002), and Moraxella catarrhalis (OR=0.21, 95%CI:0.11-0.40, P < 0.00001) in the nasopharyngeal region. Conclusions AZM adjuvant therapy can reduce the time to the relief of wheezing and cough in children with bronchiolitis, but it has no marked effect on the length of hospital stay and oxygen supply time.
CHE Si-Yi,HE Huan,DENG Yu et al. Clinical effect of azithromycin adjuvant therapy in children with bronchiolitis: a systematic review and Meta analysis[J]. CJCP, 2019, 21(8): 812-819.
Paramore LC, Ciuryla V, Ciesla G, et al. Economic impact of respiratory syncytial virus-related illness in the US:an analysis of national databases[J]. Pharmacoeconomics, 2004, 22(5):275-284.
[2]
Shi T, McAllister DA, O'Brien KL, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015:a systematic review and modelling study[J]. Lancet, 2017, 390(10098):946-958.
[3]
Caffrey Osvald E, Clarke JR. NICE clinical guideline:bronchiolitis in children[J]. Arch Dis Child Educ Pract Ed, 2016, 101(1):46-48.
[4]
Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, et al. Azithromycin:mechanisms of action and their relevance for clinical applications[J]. Pharmacol Ther, 2014, 143(2):225-245.
[5]
Hosakote YM, Jantzi PD, Esham DL, et al. Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis[J]. Am J Respir Crit Care Med, 2011, 183(11):1550-1560.
[6]
Bont L, Heijnen C, Kavelaars A, et al. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis[J]. Eur Respir J, 1999, 14(1):144-149.
[7]
Marguet C, Bocquel N, Benichou J, et al. Neutrophil but not eosinophil inflammation is related to the severity of a first acute epidemic bronchiolitis in young infants[J]. Pediatr Allergy Immunol, 2008, 19(2):157-165.
[8]
Čulić O, Eraković V, Čepelak I, et al. Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects[J]. Eur J Pharmacol, 2002, 450(3):277-289.
[9]
DeVincenzo JP, Wilkinson T, Vaishnaw A, et al. Viral load drives disease in humans experimentally infected with respiratory syncytial virus[J]. Am J Respir Crit Care Med, 2010, 182(10):1305-1314.
[10]
DeVincenzo JP, El Saleeby CM, Bush AJ. Respiratory syncytial virus load predicts disease severity in previously healthy infants[J]. J Infect Dis, 2005, 191(11):1861-1868.
[11]
Asada M, Yoshida M, Suzuki T, et al. Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells[J]. Antiviral Res, 2009, 83(2):191-200.
[12]
Gielen V, Johnston SL, Edwards MR. Azithromycin induces anti-viral responses in bronchial epithelial cells[J]. Eur Respir J, 2010, 36(3):646-654.
[13]
Desaki M, Takizawa H, Ohtoshi T, et al. Erythromycin suppresses nuclear factor-κB and activator protein-1 activation in human bronchial epithelial cells[J]. Biochem Biophys Res Commun, 2000, 267(1):124-128.
[14]
Anderson R. Erythromycin and roxithromycin potentiate human neutrophil locomotion in vitro by inhibition of leukoattractant-activated superoxide generation and autooxidation[J]. J Infect Dis, 1989, 159(5):966-973.
[15]
Tamaoki J, Nakata J, Tagaya E, et al. Effects of roxithromycin and erythromycin on interleukin 8-induced neutrophil recruitment and goblet cell secretion in guinea pig tracheas[J]. Antimicrob Agents Chemother, 1996, 40(7):1726-1728.
[16]
Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases[J]. Chest, 2010, 138(5):1202-1212.
[17]
Beigelman A, Mikols CL, Gunsten SP, et al. Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis[J]. Respir Res, 2010, 11:90.
[18]
McCallum GB, Morris PS, Chatfield MD, et al. A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis:a randomised, placebo-controlled trial[J]. PLoS One, 2013, 8(9):e74316.
[19]
Pinto LA, Pitrez PM, Luisi F, et al. Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes:a randomized, double-blinded, and placebo-controlled clinical trial[J]. J Pediatr, 2012, 161(6):1104-1108.
[20]
Beigelman A, Isaacson-Schmid M, Sajol G, et al. Randomized trial to evaluate azithromycin's effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis[J]. J Allergy Clin Immunol, 2015, 135(5):1171-1178.e1.
[21]
McCallum GB, Morris PS, Grimwood K, et al. Three-weekly doses of azithromycin for indigenous infants hospitalized with bronchiolitis:a multicentre, randomized, placebo-controlled trial[J]. Front Pediatr, 2015, 3:32.
[22]
Kneyber MC, van Woensel JB, Uijtendaal E, et al. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease:a randomized equivalence trial[J]. Pediatr Pulmonol, 2008, 43(2):142-149.
Mallia P, Johnston SL. Respiratory viruses:do they protect from or induce asthma?[J]. Allergy, 2002, 57(12):1118-1129.
[34]
Mansbach JM, Hasegawa K, Henke DM, et al. Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota[J]. J Allergy Clin Immunol, 2016, 137(6):1909-1913.e4.
[35]
Bisgaard H, Hermansen MN, Bønnelykke K, et al. Association of bacteria and viruses with wheezy episodes in young children:prospective birth cohort study[J]. BMJ, 2010, 4, 341:c4978.
