How long should we maintain long‐term azithromycin treatment in cystic fibrosis patients?

Willekens, Julie; Eyns, H.; Malfroot, Anne

doi:10.1002/ppul.22981

Cited by 12 publications

(17 citation statements)

References 6 publications

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“…material) show that the PD group demonstrated a stable improvement of FVC and FEV 1 during the first 2 years of therapy, whereas a positive treatment effect of AZ was not seen after the first year. These results are consistent with recent studies that suggest that pulmonary function improvement after AZ initiation is temporary, and that the effect is not sustained beyond the first year of treatment [18][19][20] .…”

Section: Lung Disease Progressionsupporting

confidence: 82%

“…Nevertheless, significant debate remains regarding the duration of AZ treatment. In a few open retrospective studies the positive effects of AZ have not been sustained beyond the first year of treatment, and no further clinical benefit of continuing AZ for more than 1 year has been found [18][19][20] . At the same time, nothing is known as yet about the influence of chronic therapy on inflammatory parameters in the sputum and peripheral blood of CF patients.…”

Section: Introductionmentioning

confidence: 99%

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Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Shmarina

Pukhalsky²,

Avakian³

et al. 2017

Int Arch Allergy Immunol

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Background: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. Methods: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Results: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ₁ concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Conclusions: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.

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Section: Lung Disease Progressionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Shmarina

Pukhalsky²,

Avakian³

et al. 2017

Int Arch Allergy Immunol

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“…Similarly, Willekens et al 21 found that although there was no change in pulmonary function parameters or the incidence of severe exacerbations requiring intravenous antibiotic treatment, the first year of AZM administration was associated with a significant reduction in the number of orally treated pulmonary exacerbations per patient. However, this reduction was not maintained in the second and third treatment years.…”

Section: Discussionmentioning

confidence: 99%

“…The reduced number of pulmonary exacerbations requiring courses of antibiotics documented here may be related with the anti-inflammatory properties of AZM. of longer periods of treatment, and both found that efficacy was poor after the first year 20,21 .…”

Section: Discussionmentioning

confidence: 99%

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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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Azithromycin use in patients with cystic fibrosis

Principi

Blasi

Esposito

2015

Eur J Clin Microbiol Infect Dis

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Rational antimicrobial administration is still considered to be the most effective therapeutic approach in cystic fibrosis (CF), and long-term treatment with azithromycin (Az) is included in the current guidelines for CF patients aged ≥ 6 years. Az has microbiological, immunomodulatory and anti-inflammatory properties that can reduce some of the biological problems that are among the causes of the progressive lung damage associated with CF. Moreover, although it is not active against Pseudomonas aeruginosa (the most important bacterial pathogen responsible for infectious exacerbations), it can be efficiently used in the case of P. aeruginosa infections because sub-inhibitory concentrations can reduce their pathogenic role by interfering with some bacterial activities and increasing their susceptibility to antibiotics. Az also has anti-viral activity that limits the risk of the bacterial pulmonary exacerbations that frequently occur after apparently mild viral infections. The available data seem to indicate that it is effective during its first year of administration, but the impact of longer treatment is debated. Other still undefined aspects of the use of Az include the possible emergence of antibiotic resistance in the other bacterial pathogens that usually colonise CF patients, the real incidence of adverse events and the drug's potential interference with other routine therapies.

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How long should we maintain long‐term azithromycin treatment in cystic fibrosis patients?

Cited by 12 publications

References 6 publications

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

Long term azithromycin therapy in patients with cystic fibrosis

Azithromycin use in patients with cystic fibrosis

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