长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症疗效与风险的系统评价和Meta分析

Efficacy and risk of long-term macrolides in the treatment of non-cystic fibrosis bronchiectasis:a systematic review and meta-analysis

目的评估长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症的疗效与风险。方法分别检索中国知网、万方数据、中国生物医学网、维普网、PubMed、Embase、Cochrane Library及Web of Science数据库中已发表的关于长期大环内酯类抗生素治疗非囊性纤维化支气管扩张症疗效与风险的随机对照研究。主要结局指标为急性发作频率、24 h痰量改变、炎症指标改变、菌群分布变化与菌群耐药变化。结果共纳入11项随机对照试验,长期大环内酯类抗生素治疗显著降低非囊性纤维化支气管扩张症的急性加重频率,包括至少发生一次急性加重人数(RR=0.63,95%CI:0.46~0.86,P=0.004)和人均急性加重次数(MD=-1.29,95%CI:-1.72~-0.86,P<0.00001)以及降低24 h痰量(MD=-8.10,95%CI:-12.62~-3.58,P=0.0004)。亚组分析显示,3个月以上大环内酯类抗生素治疗可有效降低成年患者急性加重频率。在3个月以下疗程亚组、红霉素治疗亚组以及儿童患者亚组中,大环内酯类抗生素未显著降低急性加重频率。患者种族差异未对治疗效果产生明显影响。基线水平常见痰菌种类及数量、治疗结束后的痰菌种类及数量、治疗结束后痰菌的增加和清除率指标在大环内酯类抗生素治疗组和对照组之间的差异均无统计学意义,但大环内酯类抗生素治疗组的痰菌耐药率显著增加。结论3个月以上大环内酯类抗生素治疗可以显著降低成人非囊性纤维化支气管扩张症患者的急性加重频率,减少24 h痰量。长期大环内酯类抗生素治疗对非囊性纤维化支气管扩张症患者痰菌分布及变化无显著影响,但有提高耐大环内酯类抗生素细菌比例的风险。

Objective To evaluate the efficacy and risk of long-term macrolides in the treatment of non-cystic fibrosis bronchiectasis.Methods Randomized controlled studies on the efficacy and risk of long-term macrolides in the treatment of non-cystic fibrosis bronchiectasis were retrieved in CNKI,Wanfang,SinoMed,VIP,PubMed,Embase,Cochrane Library and web of science.The main outcome indexes were the frequency of acute attack,the change in sputum volume in 24 hours,the change in inflammation index,the change in bacterial distribution and the change in bacterial resistance.Results A total of 11 randomized controlled trials were included.Meta-analysis showed that macrolides significantly reduced the frequency of acute exacerbation of non-cystic fibrosis bronchiectasis after long-term treatment,including the number of patients with at least one acute exacerbation(RR=0.63,95%CI:0.46~0.86,P=0.004)and the number of per capita acute exacerbations(MD=-1.29,95%CI:-1.72~0.86,P<0.00001),and the amount of 24-hour sputum was also reduced(MD=-8.10,95%CI:-12.62~-3.58,P=0.0004).Subgroup analysis showed that macrolide antibiotics for more than 3 months could effectively reduce the frequency of acute exacerbation in adult patients.Macrolides did not significantly reduce the frequency of acute exacerbation in the treatment subgroup,erythromycin treatment subgroup,and child subgroup receiving less than 3 months of treatment.Racial differences had no significant effect on the therapeutic effect.There was no significant difference in the types and numbers of common sputum bacteria at the baseline level,or the types and numbers of sputum bacteria at the end of treatment,or the increase and clearance rate of sputum bacteria at the end of treatment between the macrolide antibiotic treatment group and the control group,but the resistance rate of sputum bacteria in the macrolide antibiotic treatment group increased significantly.Conclusion Macrolide antibiotics for more than 3 months can significantly reduce the frequency of acute exacerbation and 24-hour sputum volume in adult patients with non-cystic fibrosis bronchiectasis.Long-term macrolides treatment has no significant effect on the distribution and change of sputum bacteria,but it may increase the proportion of macrolides antibiotic bacteria.