Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: A randomised trial

University Department of Medicine and Department of Infectious Disease, Mater Adult Hospital, Brisbane, Australia.
Thorax (Impact Factor: 8.29). 04/2002; 57(3):212-6.
Source: PubMed


Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.
To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.
Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).
AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.

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    • "Azithromycin treatment was also studied in CF patients. Since 2002, several studies showed improved clinical outcome of CF patients upon treatment with azithromycin [63–65]. Whether the effect of the treatment is primarily anti-infectious or primarily anti-inflammatory in patients with CF is difficult to disentangle. "
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    ABSTRACT: Since the discovery of IL-17 in 1995 as a T-cell cytokine, inducing IL-6 and IL-8 production by fibroblasts, and the report of a separate T-cell lineage producing IL-17(A), called Th17 cells, in 2005, the role of IL-17 has been studied in several inflammatory diseases. By inducing IL-8 production and subsequent neutrophil attraction towards the site of inflammation, IL-17A can link adaptive and innate immune responses. More specifically, its role in respiratory diseases has intensively been investigated. We here review its role in human respiratory diseases and try to unravel the question whether IL-17A only provides a link between the adaptive and innate respiratory immunity or whether this cytokine might also be locally produced by innate immune cells. We furthermore briefly discuss the possibility to reduce local IL-17A production as a treatment option for respiratory diseases.
    Clinical and Developmental Immunology 01/2013; 2013(12):840315. DOI:10.1155/2013/840315 · 2.93 Impact Factor
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    • "Although AZM has no bactericidal effect on P. aeruginosa, it was shown that AZM retards the formation of biofilms and blocks the bacterial quorum sensing involved in the production of biofilms [26-28]. The use of AZM to treat chronic infections of P. aeruginosa in the lungs of CF patients has been gaining favour due to the improved outcome of CF patients treated with this antibiotic [29,30]. "
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    ABSTRACT: Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF) patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC) results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC) for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P < 0.001, meropenem: P = 0.005). When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P < 0.001) and tobramycin (P < 0.001), regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.
    BMC Microbiology 09/2012; 12(1):196. DOI:10.1186/1471-2180-12-196 · 2.73 Impact Factor
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    • "Following encouraging results from a single institution case series (Jaffe, Francis, Rosenthal, & Bush, 1998), azithromycin has been evaluated in randomised controlled trials. These have demonstrated a small but significant improvement in respiratory function and a reduction in infective exacerbations (Wolter et al., 2002; Equi, Balfour-Lynn, Bush, & Rosenthal, 2002; Saiman, Marshall, Mayer-Hamblett, et al., 2003). These effects were persistent when combined in the Cochrane Group meta-analysis (Southern, Baker, & Solis-Moya, 2011). "
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    ABSTRACT: Background: Azithromycin is widely used as an immunomodulatory agent in the treatment of cystic fibrosis with previous literature documenting improvements in lung function and a reduction in infective exacerbations. The maximal study period in adults has been six months. Methods: 81 adult patients taking continuous azithromycin were retrospectively identified. Percentage predicted FEV(1) and courses of intravenous antibiotics were examined at yearly intervals two years prior to and two years after azithromycin initiation. Results: FEV(1) deteriorated in the two years before starting azithromycin by a mean of 2.02% per year. In the year following initiation, FEV(1) increased by 1.15% (P=0.01). However, a mean 2.58% reduction was observed in year two. There was no statistically significant effect on courses of intravenous antibiotics. Conclusions: Azithromycin resulted in an improved FEV(1) at year one. This effect was not sustained beyond the first year of treatment.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 07/2012; 12(1). DOI:10.1016/j.jcf.2012.05.010 · 3.48 Impact Factor
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