Long-term effects of azithromycin in patients with cystic fibrosis

被引:37
作者
Samson, Clementine [1 ,2 ]
Tamalet, Aline [1 ]
Hoang Vu Thien [3 ]
Taytard, Jessica [1 ,6 ]
Perisson, Caroline [1 ]
Nathan, Nadia [1 ]
Clement, Annick [1 ,4 ]
Boelle, Pierre-Yves [4 ,5 ]
Corvol, Harriet [1 ,4 ,6 ]
机构
[1] Hop Trousseau, AP HP, Pediat Pulmonol Dept, 26 Ave Docteur Arnold Netter, F-75012 Paris, France
[2] Besancon Hosp, Dept Pediat, Besancon, France
[3] Hop Trousseau, AP HP, Dept Bacteriol, Paris, France
[4] Univ Paris 06, Sorbonne Univ, Paris, France
[5] Hop St Antoine, AP HP, Biostat Dept, INSERM,U1136, Paris, France
[6] CRSA, INSERM, F-75012 Paris, France
关键词
Children; Cystic fibrosis; Azithromycin; Lung function; Respiratory exacerbation; Bacteria resistance; PSEUDOMONAS-AERUGINOSA; DOUBLE-BLIND; LUNG; SOLITHROMYCIN; MACROLIDES; SAFETY; MULTICENTER; NEUTROPHILS; PREVALENCE; RESISTANCE;
D O I
10.1016/j.rmed.2016.05.025
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Low-dose azithromycin has beneficial effects on severity of the lung disease in cystic fibrosis (CF) patients for a period of 6-12 months after initiation of the treatment. Although its impact in the longer term is uncertain, this treatment is frequently used chronically. The aim of this retrospective study was to investigate the effects of low-dose azithromycin treatment on the progression of CF lung disease in patients treated for more than 12 months. Methods: All of the CF patients followed in our pediatric center and who had been on low-dose azithromycin for more than 12 sequential months were included. The clinical data were collected for one year before and three years after the initiation of the azithromycin treatment. These data comprised lung function analyses, rates of exacerbations and of antibiotic courses, and changes in the airways' bacterial colonization. Results: A total of 68 patients were included (mean age: 9.95 yrs (3.61)). After 12 months, significant reductions in the numbers of pulmonary exacerbations and antibiotic courses were present. However, this effect was not maintained in the subsequent periods, during which increased rates of both pulmonary exacerbations and antibiotic courses were observed. The lung function decline was not modified during the treatment, and a decreasing time-dependent trend typical of CF was observed for the various parameters. No differences in the airway colonization by pathogens such as Pseudomonas aeruginosa and methicillin-sensitive and/or -resistant Staphyloccocus aureus were observed during the treatment. However, isolated Staphyloccocus aureus strains became resistant to macrolides after 6 months of azithromycin and remained resistant thereafter. Conclusions: No clinical benefits of low-doses azithromycin were present after one year of treatment in young CF patients. Selection for macrolide-resistant strains of bacteria occurred, which should lead to a reconsideration of the duration of azithromycin treatment in CF. (C) 2016 Elsevier Ltd. All rights reserved.
引用
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页码:1 / 6
页数:6
相关论文
共 39 条
[1]  
[Anonymous], AM J MED S9A
[2]   Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge [J].
Balloy, V. ;
Deveaux, A. ;
Lebeaux, D. ;
Tabary, O. ;
le Rouzic, P. ;
Ghigo, J. M. ;
Busson, P. F. ;
Boelle, P. Y. ;
Guez, J. Guez ;
Hahn, U. ;
Clement, A. ;
Chignard, M. ;
Corvol, H. ;
Burnet, M. ;
Guillot, L. .
BRITISH JOURNAL OF PHARMACOLOGY, 2014, 171 (07) :1783-1794
[3]   Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL) [J].
Barrera, Carlos M. ;
Mykietiuk, Analia ;
Metev, Hristo ;
Nitu, Mimi Floarea ;
Karimjee, Najumuddin ;
Doreski, Pablo Alexis ;
Mitha, Ismail ;
Tanaseanu, Cristina Mihaela ;
Molina, Joseph McDermott ;
Antonovsky, Yuri ;
Van Rensburg, Dirkie Johanna ;
Rowe, Brian H. ;
Flores-Figueroa, Jose ;
Rewerska, Barbara ;
Clark, Kay ;
Keedy, Kara ;
Sheets, Amanda ;
Scott, Drusilla ;
Horwith, Gary ;
Das, Anita F. ;
Jamieson, Brian ;
Fernandes, Prabhavathi ;
Oldach, David .
LANCET INFECTIOUS DISEASES, 2016, 16 (04) :421-430
[4]  
C. F. Foundation, 1994, MICR INF DIS CYST FI, P1
[5]   Effectiveness and safety of macrolides in cystic fibrosis patients: a meta-analysis and systematic review [J].
Cai, Yun ;
Chai, Dong ;
Wang, Rui ;
Bai, Nan ;
Liang, Bei-Bei ;
Liu, Youning .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2011, 66 (05) :968-978
[6]   Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial [J].
Clement, A. ;
Tamalet, A. ;
Leroux, E. ;
Ravilly, S. ;
Fauroux, B. ;
Jais, J-P .
THORAX, 2006, 61 (10) :895-902
[7]   Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis [J].
Corvol, H ;
Fitting, C ;
Chadelat, K ;
Jacquot, J ;
Tabary, O ;
Boule, M ;
Cavaillon, JM ;
Clement, A .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2003, 284 (06) :L997-L1003
[8]   A phase I determination of azithromycin in plasma during a 6-week period in normal volunteers after a standard dose of 500mg once daily for 3 days [J].
Crokaert, F ;
Hubloux, A ;
Cauchie, P .
CLINICAL DRUG INVESTIGATION, 1998, 16 (02) :161-166
[9]   The role of the microbiome in exacerbations of chronic lung diseases [J].
Dickson, Robert P. ;
Martinez, Fernando J. ;
Huffnagle, Gary B. .
LANCET, 2014, 384 (9944) :691-702
[10]   Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial [J].
Equi, A ;
Balfour-Lynn, IM ;
Bush, A ;
Rosenthal, M .
LANCET, 2002, 360 (9338) :978-984