Buccal Adherence of Pseudomonas aeruginosa in Patients with Cystic Fibrosis under Long-Term Therapy with Azithromycin

Baumann, Ulrich; Fischer, J.J.; Gudowius, Peter; Lingner, Meike; Herrmann, Susanne; Tümmler, Burkhard; Hardt, H. von der

doi:10.1007/s15010-001-0031-3

Cited by 44 publications

(23 citation statements)

References 30 publications

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“…Second generation macrolides, especially azithromycin, are used as low‐dose continuous treatment in CF, especially in patients chronically infected with PA 15, 28. In the children <19 years, we found a higher use of macrolides in girls compared to boys.…”

Section: Discussionmentioning

confidence: 63%

Gender differences in the Scandinavian cystic fibrosis population

Olesen¹,

Pressler²,

Hjelte³

et al. 2010

Pediatric Pulmonology

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AimsTo explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication.MethodsCross‐sectional data on 890 (416 female) pancreatic insufficient CF patients were evaluated regarding chronic infection, body mass index, lung function, medication, and diabetes, as well as data of Pseudomonas infection status, antibiotic treatment and hospitalization from 1‐year follow‐up.ResultsWe found no differences in lung function, body mass index, or frequency of diabetes. The adult group consisted of more males than females (208:168). We found no significant difference in prevalence of chronic Pseudomonas aeruginosa infection, but during the follow‐up the incidence of new chronic infection was higher in adult females (10/33 vs. 4/56). Females had higher prevalence of Burkholderia infection (21/416 vs. 11/474). Adult females had more days on intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital (median 2 vs. 0 days/year). More adult females received inhaled and oral steroids. In the pediatric cohort, females were treated more often with macrolides as an anti‐inflammatory agent.ConclusionWe found no gender difference in key clinical parameters in our CF population. However, our study showed a higher risk of Pseudomonas and Burkholderia infection among the female patients. Additionally, we found that female patients require more intensified treatment regarding antibiotics, macrolides, steroids and days of hospitalization, indicating a true female disadvantage even with modern aggressive treatment. The finding of more males than females in the adult population suggesting a male advantage, warrants a mortality study. Pediatr Pulmonol. 2010; 45:959–965. © 2010 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 63%

Gender differences in the Scandinavian cystic fibrosis population

Olesen¹,

Pressler²,

Hjelte³

et al. 2010

Pediatric Pulmonology

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“…Baumann et al studied the effect of roxithromycin by using a model of P. aeruginosa adherence to buccal epithelial cells from 11 CF children (25). Increased adherence was found in CF patients, and 3 months of azithromycin therapy decreased the adherence to normal control levels.…”

Section: Inhibition Of Adherencementioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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“…Several anti-inflammatory mechanisms of macrolide antibiotics have been proposed, such as suppression of neutrophil chemotactic activity, decrease in serum immune complexes, reduction of sputum viscosity and reduction in adherence of P. aeruginosa [3,4], yet their mode of action remains unclear. In several recently published studies, long-term, low-dose azithromycin (AZM) treatment in CF patients has significantly improved lung function and reduced the number of acute respiratory exacerbations [5][6][7][8][9]. This effect may be due to AZM's anti-inflammatory action or sub-MIC inhibition of the micro-organisms [10].…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies against bactericidal/permeability–increasing protein (BPI–ANCA) in cystic fibrosis patients treated with azithromycin

et al. 2005

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Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) were found in patients with cystic fibrosis (CF). It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM), through its antiinflammatory effect, could affect the level of BPI-ANCA in CF patients. Eighteen patients with CF aged 5.5-36.3 years (median 15.1) were enrolled in a randomised, double-blind, placebo-controlled trial of AZM (250 mg twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI-ANCA levels were recorded pre- and post-treatment and compared to a group of 18 matched healthy controls. Chi-square analysis, Kruskal-Wallis and Mann-Whitney tests were used to compare between the groups. Pre- and post-treatment values were compared using the Wilcoxon Signed-Ranked test. BPI-ANCA was found in 12 CF patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI-ANCA level was 3.94+/-6.15 U/ml (mean+/-SD) in healthy subjects and 38.11+/-42.34 U/ml in CF patients (P=0.023). The mean BPI-ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without (64+/-35 U/ml and 25+/-41 U/ml respectively, P=0.032). No change in BPI-ANCA levels occurred in the AZM-treated patients [35 (0-127) U/ml (median (range) and 30 (0-120) U/ml, respectively] or in the placebo group [10 (0-66) U/ml and 13 (0-83) U/ml, respectively]. BPI-ANCA levels are significantly higher in patients with CF compared to healthy controls. BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve weeks of AZM therapy did not lower the BPI-ANCA level in patients with CF.

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Buccal Adherence of Pseudomonas aeruginosa in Patients with Cystic Fibrosis under Long-Term Therapy with Azithromycin

Abstract: Long-term low-dose AZM therapy may improve the compromised oropharyngeaL barrier function in patients with CF, opening new perspectives for early treatment of P. aeruginosa infection in CF.

Cited by 44 publications

References 30 publications

Gender differences in the Scandinavian cystic fibrosis population

Gender differences in the Scandinavian cystic fibrosis population

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Autoantibodies against bactericidal/permeability–increasing protein (BPI–ANCA) in cystic fibrosis patients treated with azithromycin

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