Daily versus weekly azithromycin in cystic fibrosis patients

McCormack, J. G.; Bell, Scott C.; Senini, S.; Walmsley, Konstantin; Patel, KK; Wainwright, Claire; Serisier, David J.; Harris, Michael T.; Bowler, Simon

doi:10.1183/09031936.00163306

Cited by 51 publications

(35 citation statements)

References 15 publications

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“…The possibility that macrolides might modify the neutrophilic inflammatory response in CF was first investigated in the early 2000s. Since then, a number of clinical trials have confirmed their beneficial effects both in adults and children [31][32][33][34][35][36][37]. Recently, in a multicentre, randomised, double-blind, placebo-controlled trial, 260 CF patients, not infected with P. aeruginosa, were randomised in a 1:1 ratio to azithromycin 250 mg or 500 mg (based on body weight) 3 days per week, or placebo, for a period of 24 weeks.…”

Section: Cystic Fibrosismentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

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Long-term macrolide treatment was first shown to alter the natural history of diffuse panbronchiolitis (DPB) in the late 1980s. Since then, macrolides have been demonstrated to exert antiinflammatory and immunomodulatory activity in addition to being antimicrobial. Indeed, their spectrum of action extends to the regulation of leukocyte function and production of inflammatory mediators, control of mucus hypersecretion, resolution of inflammation and modulation of host defence mechanisms. As such, the potential benefit of macrolide antibiotics has been evaluated in a variety of chronic respiratory diseases. The best studied condition is cystic fibrosis, of which there have been six randomised controlled trials showing evidence of benefit. However, most of the studies were limited by small numbers of patients and short follow-up. More recently, landmark studies have demonstrated the efficacy of azithromycin in reducing the risk of acute exacerbations in patients with chronic obstructive pulmonary disease, but the optimal duration and dosing of macrolide treatment remain uncertain.With the exception of patients with DPB and cystic fibrosis, until clear evidence of efficacy is available, the long-term use of macrolides should be limited to highly selected patients after careful evaluation of benefit and harm, or in the context of randomised controlled clinical trials. @ERSpublications Several studies evaluating macrolide antibiotics for the treatment of chronic respiratory diseases are underway

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Section: Cystic Fibrosismentioning

confidence: 99%

Long-term macrolide treatment for chronic respiratory disease

2012

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“…The mechanism of macrolides effect on CF lung disease is unknown. The possibility that macrolides might modify the neutrophilic inflammatory response in CF was investigated and their beneficial effects have been confirmed in a number of clinical trials both in adults and children [12][13][14][15][16][17][18] .…”

Section: Discussionmentioning

confidence: 99%

Long term azithromycin therapy in patients with cystic fibrosis

Emiralioğlu¹,

Öztürk²,

Yalçın³

et al. 2016

Turk J Pediatr

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Inflammation is a central contributor to the pathogenesis of cystic fibrosis (CF) pulmonary disease; so limiting the excessive production of inflammatory mediators represents a major therapeutic strategy for slowing the decline in lung function and improving survival. The macrolide antibiotic azithromycin (AZM) has anti-inflammatory properties and immunomodulatory effects that may be beneficial in CF. The aim of this study was to document the long term use of AZM effect on pulmonary function, nutritional status and number of pulmonary exacerbations in patients with CF. Twenty four patients with CF aged 4-23 years followed at Hacettepe University Department of Pediatric Pulmonology between May 2007-December 2014enrolled in the study from 630 CF patients. They received 10 mg/kg/day of AZM three times a week. Pulmonary function parameters, sputum cultures, body mass index (BMI) Z scores and number of pulmonary exacerbations were analyzed at different time intervals (at the visits at months 6, 9 and 12).Median age of the patients was 14.7 (range 4-23 years) years and median treatment duration was 14 months (range 6-60 months). Initially, median FEV1% was found 68% (range 30%-100%), BMI was found 17.05 (range 13.3-26.5) and oxygen saturation was found 95% (range 84%-99%). At the end of the 6th, 9th and 12th months of the AZM therapy; no significant differences in FEV1% and oxygen saturation parameters were found compared to the initial time, however BMI increased significantly (p=0.03), also the number of pulmonary exacerbations (p<0.001) and severe exacerbations (p<0.001) needing intravenous antibiotic treatment were significantly reduced at the 6th and 12th month. At the end of the 12th month of AZM; Methicillin sensitive S. aureus (MSSA) colonization was significantly increased (p=0.005) and increased macrolide resistance was detected (p=0.008).Although, this study could not be designed as a placebo controlled study, the results showed that at least 6 months of AZM treatment led to a significiant reduction in the number of pulmonary exacerbations requiring antibiotics and improvement on nutritional status. Despite increased P. aeruginosa antibiotic resistance and MSSA colonization rates, the lower incidence of acute exacerbations in patients receiving AZM is an important and clinically relevant measure of beneficial effect. Therefore, long term use of AZM may be considered to slow pulmonary deterioration in CF patients with P. aeruginosa colonization.

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“…(29,30) In addition, it is essential to bear in mind the possibility that resistance to macrolides and other antibiotics will increase, as well as the clinical impact of colonization with more resistant pathogens. (18)(19)(20) …”

Section: Cystic Fibrosismentioning

confidence: 99%

“…McCormack et al (19) RCT Equivalence was demonstrated between the two groups (daily vs. weekly use) with respect to improvements in pulmonary function. Phaff et al (17) RCT Erythromycin resistance in S. aureus isolates increased, as did clarithromycin resistance in H. influenzae isolates.…”

Section: Rctmentioning

confidence: 99%

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Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

et al. 2012

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Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.Keywords: Macrolides; Asthma; Cystic Fibrosis; Bronchiolitis. ResumoOs macrolídeos são fármacos com efeitos antimicrobianos especialmente contra patógenos intracelulares. Vários estudos têm demonstrado possíveis efeitos anti-inflamatórios dos macrolídeos. Esses medicamentos inibem a produção de algumas interleucinas e podem reduzir a inflamação neutrofílica pulmonar. Ensaios clínicos têm demonstrado efeitos benéficos dos macrolídeos em diversas doenças pulmonares crônicas. O objetivo deste estudo foi revisar os dados recentes da literatura médica sobre os efeitos anti-inflamatórios dos macrolídeos nas doenças respiratórias da infância, através da pesquisa da base de dados Medline (PubMed) dos seguintes termos em inglês: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; e "macrolide and acute bronchiolitis" Foram selecionados artigos publicados em revistas científicas internacionais entre 2001 e 2012. Estudos clínicos e evidências in vitro comprovam o efeito anti-inflamatório dos macrolídeos em doenças respiratórias. Alguns ensaios clínicos demonstram benefícios na administração de macrolídeos em pacientes com fibrose cística; porém, o risco de resistência bacteriana deve ser considerado na análise desses benefícios. Tais benefícios são controversos em outras doenças respiratórias, e seu uso rotineiro não está indicado. Mais estudos clínicos controlados são necessários para avaliar a eficácia desses medicamentos como anti-inflamatórios. Dessa forma, poderemos d...

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Daily versus weekly azithromycin in cystic fibrosis patients

Cited by 51 publications

References 15 publications

Long-term macrolide treatment for chronic respiratory disease

Long-term macrolide treatment for chronic respiratory disease

Long term azithromycin therapy in patients with cystic fibrosis

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

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