Azithromycin for Early <i>Pseudomonas</i> Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial

Mayer-Hamblett, Nicole; Retsch‐Bogart, George; Kloster, Margaret; Accurso, Frank J.; Rosenfeld, Margaret; Albers, Gary M.; Black, Philip; Brown, Perry; Cairns, AnneMarie; Davis, Stephanie D.; Graff, Gavin R.; Kerby, Gwendolyn S.; Orenstein, David M.; Buckingham, Rachael; Ramsey, Bonnie W.

doi:10.1164/rccm.201802-0215oc

Cited by 84 publications

(58 citation statements)

References 46 publications

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“…Most recently, azithromycin reduced the time to next exacerbation in young children with CF who developed newly identified P aeruginosa in respiratory cultures. It did not reduce the risk of developing chronic P aeruginosa infection or the time to next acquisition of P aeruginosa …”

Section: Cellular Contributions To the Cf Airway Inflammatory Responsementioning

confidence: 92%

“…It did not reduce the risk of developing chronic P aeruginosa infection or the time to next acquisition of P aeruginosa. 183 Regardless of the mechanism(s) of action, the proven clinical benefits of chronic azithromycin in the CF population have resulted in widespread use. According to the CFFPR, nearly 70% of those with chronic P aeruginosa infection are prescribed this therapy in the United States.…”

Section: Azithromycinmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation in cystic fibrosis: An update

Roesch

Nichols

Chmiel

2018

Pediatric Pulmonology

198

221

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Inflammation plays a critical role in cystic fibrosis (CF) lung pathology and disease progression making it an active area of research and important therapeutic target. In this review, we explore the most recent research on the major contributors to the exuberant inflammatory response seen in CF as well as potential therapeutics to combat this response. Absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) alters anion transport across CF airway epithelial cells and ultimately results in dehydration of the airway surface liquid. The dehydrated airway surface liquid in combination with abnormal mucin secretion contributes to airway obstruction and subsequent infection that may serve as a trigger point for inflammation. There is also evidence to suggest that airway inflammation may be excessive and sustained relative to the infectious stimuli. Studies have shown dysregulation of both pro-inflammatory mediators such as IL-17 and pro-resolution mediators including metabolites of the eicosanoid pathway. Recently, CFTR potentiators and correctors have garnered much attention in the CF community. Although these modulators address the underlying defect in CF, their impact on downstream consequences such as inflammation are not known. Here, we review pre-clinical and clinical data on the impact of CFTR modulators on inflammation. In addition, we examine other cell types including neutrophils, macrophages, and T-lymphocytes that express CFTR and contribute to the CF inflammatory response. Finally, we address challenges in developing anti-inflammatory therapies and highlight some of the most promising anti-inflammatory drugs under development for CF.

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Section: Cellular Contributions To the Cf Airway Inflammatory Responsementioning

confidence: 92%

Section: Azithromycinmentioning

confidence: 99%

Inflammation in cystic fibrosis: An update

Roesch

Nichols

Chmiel

2018

Pediatric Pulmonology

198

221

View full text Add to dashboard Cite

show abstract

“…In our study, improved weight gain was noted with nebulized azithromycin. Weight gain associated with azithromycin has been reported (26,27). Mayer-Hamblett et al evaluated the effects of addition of oral azithromycin to inhaled tobramycin as eradication regimen of new PA (26).…”

Section: Discussionmentioning

confidence: 99%

“…Weight gain associated with azithromycin has been reported (26,27). Mayer-Hamblett et al evaluated the effects of addition of oral azithromycin to inhaled tobramycin as eradication regimen of new PA (26). The authors observed decreased pulmonary exacerbations and increased weight in the azithromycin group.…”

Section: Discussionmentioning

confidence: 99%

Nebulized Azithromycin Versus Oral Azithromycin as Anti-Inflammatory Therapy in Children with Cystic Fibrosis: A Prospective Randomized Open-Label Trial

et al. 2019

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Background: Oral azithromycin is recommended as anti-inflammatory therapy for patients with cystic fibrosis (CF) 6 years of age and older to improve lung function and reduce exacerbations. Objectives: We evaluated the short-term efficacy and safety of nebulized azithromycin as anti-inflammatory therapy in children with CF chronically infected with Pseudomonas aeruginosa. Methods: In a randomized prospective study, children aged 8-18 years with clinically stable CF and FEV1 25%-75% predicted with no recent use of oral, intravenous or inhaled antipseudomonal antibiotics and azithromycin were randomized to receive either nebulized azithromycin (70 mg daily) or oral azithromycin 3 times per week for 28 days. Primary endpoint was changes in pulmonary function (FEV1). Secondary outcomes included changes in Pseudomonas aeruginosa (PA) colonization characteristics (count, phenotype), quality of life and weight. Results: A total of 280 patients were screened, of whom 60 were found eligible. Forty five patients (25 in the nebulized group) and 20 in the oral group) completed the study. After 28 days of treatment, nebulized azithromycin was significantly associated with improvements in FEV1 % predicted, quality of life measure and weight. Also PA count was significantly decreased. Importantly, improvements of FEV1 % predicted, quality of life, weight and the decline in PA count were statistically significantly greater with nebulized azithromycin compared with oral azithromycin. No significant difference was observed in PA phenotype in either treatment arms. Conclusions: Nebulized azithromycin is associated with a significant improvement in lung function, PA count, quality of life and weight in clinically stable CF children with chronic PA infection. The improvements observed were greater compared with oral azithromycin. Nebulized azithromycin could be suggested as a new therapeutic strategy for this life-limiting disease. Further clinical trials with novel nebulizer formulation of azithromycin and large number of participants are needed to further assess the efficacy, safety and sustained effect of this new therapeutic approach in children with CF.

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“…Azithromycin is widely used in people with CF, but its effects are still being characterized. The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double‐blind, randomized, placebo‐controlled, 18‐month trial in children with CF, 6 months to 18 years of age, with early PA respiratory tract infection . Early infection was defined as a documented new positive oropharyngeal, sputum, or lower‐respiratory‐tract culture for PA within 40 days of the baseline visit, which was either the first lifetime documented PA‐positive culture or PA recovered after at least 2 years of PA‐negative cultures with at least one culture documented per year.…”

Section: Pulmonary Healthmentioning

confidence: 99%