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The relationship between serum and sputum levels of azithromycin and clinical endpoints in patients with bronchiectasis using azithromycin maintenance treatment

Published on: 16th July, 2019

OCLC Number/Unique Identifier: 8185500244

Background: Azithromycin (AZM) is a macrolide antibiotic with distinct pharmacokinetic properties and is increasingly used as maintenance treatment in patients with bronchiectasis in order to reduce infectious exacerbations and improve pulmonary symptoms. The exact mechanism of action is not known and the relation between azithromycin dose level, local and systemic drug levels and clinical effect however, has not been extensively studied yet. Objectives: To explore the relation between AZM serum and sputum concentrations, clinical effect parameters and side effects. Methods: Azithromycin concentrations were measured in serum and sputum samples of bronchiectasis patients receiving one year of AZM treatment (250mg OD) enrolled in the Bronchiectasis and Azithromycin Treatment (BAT) trial, a double blind, randomised placebo-controlled trial. Results were correlated with data on AZM dose level, exacerbation frequency, lung function (forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), quality of life and symptoms collected within the same year. Results: 83 sputum samples from 31 patients and 151 serum samples from 43 patients were available for analysis. Mean AZM dose-level ranged from 18.8 to 39.8 mg/kg body weight/ week, generating mean AZM concentrations of 7.57 mg/L (SD 9.49) in sputum and 0.11 mg/L (SD 0.085) in serum. No correlation was found between side effects and AZM dose level, sputum- or serum concentrations. Significant correlation was found between AZM sputum concentration and CRP-level (r= -0.6). Conclusion: High and stable AZM sputum levels were reached during long term treatment, as opposed to low AZM levels in serum. Apart from CRP-levels to AZM sputum concentration, no other outcome parameter showed significant correlation to AZM serum- or sputum levels. AZM dose- or exposure levels were not predictive for the occurrence of side effects.
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Neurocognitive and Adaptive Functioning in Young Patients with Severe Chronic Kidney Disease

Published on: 11th June, 2024

Background: To assess the association between neurocognitive functioning, adaptive functioning, and health-related quality of life (HRQoL), in Children and Young Adults with Severe Chronic Kidney Disease (CKD).Methods: We included patients with severe CKD (stages 4 and 5), aged 8-30 years, on different therapy modalities (pre-dialysis, dialysis, and transplanted) and healthy controls matched on age, sex, and parental education. All patients and healthy controls performed tasks to assess neurocognitive functioning (WISC/WAIS and a comprehensive neuropsychological test battery), and completed questionnaires to assess adaptive functioning (WFIRS or WHODAS) and HRQoL (PedsQL). Group differences were explored using MANCOVA. Mediation analyses were done to explore whether the relation between neurocognitive functioning and HRQoL was mediated by adaptive functioning. Results: 28 patients with severe CKD and 21 healthy matched controls were included. CKD patients had worse HRQoL (p < .001) than healthy controls. Adaptive functioning problems increased with age in the CKD patient group but not in the healthy control group (significant interaction effect: p = .024). Significant mediation effects were found, where impaired adaptive functioning mediated the relation between both low estimated Full Scale Intelligence Quotient (eFSIQ) and worse Processing Speed & Working Memory, and impaired HRQoL (eFSIQ: 95% confidence interval = .01-.58; Processing Speed & Working Memory: 95% confidence interval = 2.31-16.36).Conclusion: We found that impaired neurocognitive functioning is associated with worse HRQoL, which is conditional to impaired adaptive functioning. Especially towards young adulthood problems in adaptive functioning are more likely to be reported than when patients are younger.
Cite this ArticleCrossMarkPublonsHarvard Library HOLLISGrowKudosResearchGateBase SearchOAI PMHAcademic MicrosoftScilitSemantic ScholarUniversite de ParisUW LibrariesSJSU King LibrarySJSU King LibraryNUS LibraryMcGillDET KGL BIBLiOTEKJCU DiscoveryUniversidad De LimaWorldCatVU on WorldCat
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