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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    • "Adherence to long term antibiotics has been described in the literature. Management of cystic fibrosis reported 30% adherence to antibiotic therapy (Wolter et al. 2002) whilst an extended nine month antibiotic treatment period for management of tuberculosis (TB) reported 42%-46% adherence (Hirsch-Moverman et al. 2015). Medication adherence research has been limited in patients with cirrhosis. "
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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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    • "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.
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