Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study

Hansen, C.R.; Pressler, Tacjana; Koch, Christian; Høiby, Niels

doi:10.1016/j.jcf.2004.09.001

Cited by 98 publications

(75 citation statements)

References 29 publications

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“…Similar findings were reported for cystic fibrosis patients infected with P. aeruginosa (309)(310)(311), where improved lung function in children was seen following six to 15 months of azithromycin (AZM) treatment. This was an unexpected finding, considering the high levels of resistance that P. aeruginosa shows toward these drugs, and general anti-inflammatory effects associated with macrolides were suggested to account for the positive results (312).…”

Section: Antibiotics As Qs Inhibitorssupporting

confidence: 77%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

693

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Antibiotics As Qs Inhibitorssupporting

confidence: 77%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

693

556

View full text Add to dashboard Cite

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“…The finding of a beneficial effect of azithromycin on pulmonary function has been reported in several smaller studies [26,[28][29][30]. A Cochrane review of macrolide therapy undertaken in 2004 concluded that treatment with azithromycin had a small but significant effect on pulmonary function in patients with cystic fibrosis [23].…”

Section: Clinical Trialsmentioning

confidence: 88%

Long-term macrolide therapy in chronic inflammatory airway diseases

Crosbie¹,

Woodhead²

2008

Eur Respir J

121

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In addition to direct antibacterial actions, 14-and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis.A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions.A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects.Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

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“…In addition, gender, steroid treatment and macrolide treatment were identified as risk-indicator variables for serum total IgG levels. Long-term treatment with macrolide antibiotics was previously shown to positively affect lung function (Hansen et al, 2005;Anwar et al, 2008) and exert complex immunomodulatory effect (Shinkai et al, 2008;Steinkamp et al, 2008), which justified inclusion of this variable into our model. Surprisingly, macrolide treatment showed a positive and a negative relation to serum total IgG and FEV1, respectively, probably as a result of selection bias and little immunomodulatory effect.…”

Section: Inverse Relation Between Vitamin D and Serum Igg T Pincikovamentioning

confidence: 92%

Inverse relation between vitamin D and serum total immunoglobulin G in the Scandinavian Cystic Fibrosis Nutritional Study

Pincikova

Nilsson²,

Moen³

et al. 2010

Eur J Clin Nutr

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Background/Objectives: The hallmark of cystic fibrosis (CF) is chronic lung inflammation. The severity of lung disease is closely correlated with immunoglobulin G (IgG) levels. Beyond its contribution to the bone health, the importance of vitamin D has not been fully recognized owing to the lack of human studies providing evidence of its benefit. In the context of the recently described immunomodulatory functions of vitamin D, we aimed to assess the relationship between vitamin D and IgG levels. Subjects/Methods: Eight hundred and ninety-six CF patients were included (0.53-65.9 years) from seven centers in Denmark, Norway and Sweden. Serum 25-hydroxyvitamin D (25OHD) and total IgG were measured, spirometry was carried out and vitamin D intake data were gathered using a 7-day dietary food record. Multiple linear regression analyses were performed for IgG and forced expiratory volume in 1ls (FEV1) as dependent variables, and serum 25OHD, daily food and supplemented vitamin D sources of intake as independent variables. The model was controlled for age, gender, genotype, CF-related diabetes, season, infection/colonization status, long-term oral corticosteroid treatment, long-term treatment with macrolide antibiotics, pancreatic insufficient phenotype and body mass index z-score. Results: Serum total IgG levels were negatively associated with serum 25OHD (adjusted R 2 ¼ 0.376; beta ¼ À0.02; Po0.001), supplemented vitamin D intake per kg bodyweight (adjusted R 2 ¼ 0.375; beta ¼ À0.82; Po0.001) and total vitamin D intake per kg bodyweight (adjusted R 2 ¼ 0.398; beta ¼ À0.60; P ¼ 0.002). Serum 25OHD was positively associated with FEV1 (adjusted R 2 ¼ 0.308; beta ¼ 0.0007; P ¼ 0.025). Conclusions: Increasing vitamin D intake may positively modulate inflammation in CF. This study supports the proposed role of vitamin D in the immune system during infection and substantiates prospective studies.

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Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study

Abstract: Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.

Cited by 98 publications

References 29 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Long-term macrolide therapy in chronic inflammatory airway diseases

Inverse relation between vitamin D and serum total immunoglobulin G in the Scandinavian Cystic Fibrosis Nutritional Study

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