大环内酯类抗生素对非囊性纤维化支气管扩张有利:BAT随机对照试验

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大利亚与荷兰学者的两项研究（即BLESS和BAT研究）表明，在非囊性纤维化支气管扩张患者中，长期使用低剂量大环内酯类（红霉素和阿奇霉素）治疗可降低肺部感染加重发生率，但亦可升高大环内酯类耐药率。

BAT研究共纳入83例在过去一年出现3次及以上下呼吸道感染的非囊性纤维化支气管扩张患者，并随机给予为期12个月的阿奇霉素（250mg/d）或安慰剂治疗。主要转归为感染加重次数。

结果为，阿奇霉素组和安慰剂组中位感染加重次数分别为0和2次（P<0.001），至少出现1次加重的患者分别大46%和80%（图2）。在随时间唯一的1秒钟用力呼气容积变化方面，阿奇霉素组每3个月升高1.03%，安慰机组每3个月降低0.10%。阿奇霉素组和安慰剂组患者胃肠道不良反应发生率分别为40%和5%。大环内酯类耐药的发生率分别为88%和26%。

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作者 ： Josje Altenburg ,Casper S de Graaff ,Ymkje Stienstra ,Jacobus H Sloos ,Eric H J van Haren ,Ralph J H Koppers

期刊名称：美国医学会杂志(JAMA)

发表时间：2013-03-27

索引：JAMA.2013 Mar 27;309(12):1251-9.

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IMPORTANCE
Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis.

OBJECTIVE
To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis.

DESIGN, SETTING, AND PARTICIPANTS
The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year.

INTERVENTIONS
Azithromycin (250 mg daily) or placebo for 12 months.

MAIN OUTCOME MEASURES
Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life.

RESULTS
Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group.

CONCLUSIONS AND RELEVANCE
Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered.

TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00415350.

爱做梦的猪宝

不管什么药，用久了或者用多了，产生耐药是必然的。