zithromax and Bronchiectasis

Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic.

Topics: Adrenal Cortex Hormones; Adult; Antifungal Agents; Asthma; Azithromycin; Bronchiectasis; Child; Humans

The efficacy of azithromycin to prevent exacerbation for non-cystic fibrosis bronchiectasis remains controversial. We conduct this meta-analysis to explore the influence of azithromycin versus placebo for the treatment of non-cystic fibrosis bronchiectasis.. We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy of azithromycin versus placebo for non-cystic fibrosis bronchiectasis. This meta-analysis was performed using the random-effect model.. Four RCTs were included in the meta-analysis. Overall, compared with control group for non-cystic-fibrosis bronchiectasis, azithromycin treatment was associated with improved free of exacerbation (odd ratios [OR] = 3.66; 95% confidence interval [CI] = 1.69-7.93; P = 0.001), reduced pulmonary exacerbations (OR = 0.27; 95% CI 0.13-0.59; P = 0.001) and number of pulmonary exacerbations (standard mean difference [SMD] =  - 0.87; 95% CI - 1.21 to - 0.54; P < 0.00001), but demonstrate no obvious impact on forced expiratory volume in 1 s (FEV1), score on St George's respiratory questionnaire, nausea or vomiting, adverse events.. Azithromycin is effective to prevent exacerbation of non-cystic fibrosis bronchiectasis.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Fibrosis; Forced Expiratory Volume; Humans; Randomized Controlled Trials as Topic

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes included changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10-0.87), mean number of exacerbations per patient (mean difference, - 1.40; 95% CI, - 2.26 to - 0.54), and sputum purulence score (mean difference, - 0.78; 95% CI, - 1.32 to - 0.24). However, long-term macrolide treatment was accompanied by an increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children; however, there are risks of increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchiectasis; Child; Disease Progression; Drug Resistance, Bacterial; Humans; Macrolides; Odds Ratio; Protein Synthesis Inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Risk; Treatment Outcome

The first clinical indication of non-antibiotic benefits of macrolides was in the Far East, in adults with diffuse panbronchiolitis. This condition is characterised by chronic airway infection, often with Pseudomonas aeruginosa, airway inflammation, bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition, and abrogated the neutrophilic airway inflammation characteristic of the disease. This dramatic finding sparked a flurry of interest in the many hundreds of macrolides in nature, especially their anti-inflammatory and immunomodulatory effects. The biggest subsequent trials of azithromycin were in cystic fibrosis, which has obvious similarities to diffuse panbronchiolitis. There were unquestionable improvements in lung function and pulmonary exacerbations, but compared to diffuse panbronchiolitis, the results were disappointing. Case reports, case series and some randomised controlled trials followed in other conditions. Three trials of azithromycin in preschool wheeze gave contradictory results; a trial in pauci-inflammatory adult asthma, and a trial in non-cystic fibrosis bronchiectasis both showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. There is clearly a huge risk of antibacterial resistance if macrolides are used widely and uncritically in the community. In summary, Azithromycin is not the answer to anything in paediatric respiratory medicine; the paediatric respiratory community needs to refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis, use modern - omics technologies to determine the endotypes of inflammatory diseases and discover in nature or synthesise designer macrolides to replicate the diffuse panbronchiolitis results. We must now find out how to do better!

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Bronchiolitis, Viral; Child; Child, Preschool; Ciliary Motility Disorders; Cystic Fibrosis; Disease Progression; Drug Resistance, Bacterial; Haemophilus Infections; Humans; Infant; Lung Diseases, Interstitial; Lung Transplantation; Macrolides; Respiratory Sounds; Stem Cell Transplantation

The social and medical costs of bronchiectasis in children are becoming considerable due to its increasing prevalence. Early identification and intensive treatment of bronchiectasis are needed to decrease the morbidity and mortality associated with bronchiectasis in children.. This review presents the current pharmacotherapeutic strategies for treating bronchiectasis in children with a focus on non-cystic fibrosis bronchiectasis.. Evidence for the effectiveness of diverse treatment strategies in bronchiectasis is lacking, particularly in children, although the disease burden is substantial for bronchiectasis. Most treatment strategies for non-cystic fibrosis bronchiectasis in children have been extrapolated from those in adults with bronchiectasis or children with cystic fibrosis. Antibiotics combined with an active airway clearance therapy via the inhalation of mucoactive agents can stabilize bronchiectasis. The timely and intensive administration of antibiotics during acute exacerbation of bronchiectasis is essential to prevent its progression in children. To suppress the bacterial loads in the airway, systemic or inhaled antibiotics can be administered intermittently or continuously. However, studies on these protocols, including the appropriate duration and effective dosages are lacking. Long-term administration of azithromycin for 12-24 months may reduce the exacerbation frequency with the increased carriage rate of azithromycin-resistant bacteria.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child; Disease Progression; Humans

Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life. Further evidence is required on the efficacy of macrolides in terms of specific bacterial eradication and the extent of antibiotic resistance.. To determine the impact of macrolide antibiotics in the treatment of adults and children with bronchiectasis.. We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted all searches on 18 January 2018.. We included randomised controlled trials (RCTs) of at least four weeks' duration that compared macrolide antibiotics with placebo or no intervention for the long-term management of stable bronchiectasis in adults or children with a diagnosis of bronchiectasis by bronchography, plain film chest radiograph, or high-resolution computed tomography. We excluded studies in which participants had received continuous or high-dose antibiotics immediately before enrolment or before a diagnosis of cystic fibrosis, sarcoidosis, or allergic bronchopulmonary aspergillosis. Our primary outcomes were exacerbation, hospitalisation, and serious adverse events.. Two review authors independently screened the titles and abstracts of 103 records. We independently screened the full text of 40 study reports and included 15 trials from 30 reports. Two review authors independently extracted outcome data and assessed risk of bias for each study. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures as expected by Cochrane.. We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin.We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention.In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I. Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child, Preschool; Clarithromycin; Erythromycin; Humans; Macrolides; Randomized Controlled Trials as Topic; Roxithromycin

Manipulation of the intestinal microbiota has been linked to weight changes and obesity. To explore the influence of specific agents that alter the intestinal flora on weight in different patient groups we conducted a meta-analysis of randomized controlled trials (RCTs) reporting on the effects of probiotics, prebiotics, synbiotics, and antibiotics on weight. We searched the Pubmed and Cochrane Library databases for trials on adults, children, and infants evaluating the effects of these substances on weight. Our primary outcome was weight change from baseline. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. We identified and included 13 adult, 17 children, and 23 infant RCTs. Effects were opposite among adults and children, showing weight loss among adults (SMD -0.54 [-0.83, -0.25)) and minor weight gains among children (SMD 0.20 [0.04, 0.36]) and infants (SMD 0.30 [-0.01, 0.62]) taking mainly Lactobacillus probiotic supplements. Heterogeneity was substantial in the adult and infant analyses and could not be explained by intervention or patient characteristics. Azithromycin administration in children with pulmonary disease was associated with weight gain (SMD 0.39 [0.24, 0.54]), without heterogeneity. A high risk of selective reporting and attrition bias was detected across the studies, making it difficult to draw firm conclusions. Overall, our meta-analysis suggests that there may be a role for probiotics in promoting weight loss in adults and weight gain in children, however additional studies are needed. Though we cannot recommend antibiotic administration for weight manipulation, its use provides advantageous weight gain in children with cystic fibrosis and bronchiectasis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child; Child, Preschool; Gastrointestinal Microbiome; Humans; Infant; Lactobacillus; Lung Diseases; Meta-Analysis as Topic; Obesity; Placebo Effect; Prebiotics; Probiotics; Randomized Controlled Trials as Topic; Synbiotics; Weight Gain; Weight Loss

Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.

Topics: Administration, Inhalation; Aerosols; Animals; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; Cystic Fibrosis; Erythromycin; Humans; Ketolides; Lung; Macrolides; Pulmonary Disease, Chronic Obstructive; Rats

Macrolide antibiotics have anti-inflammatory and immunomodulatory properties in addition to antibacterial activity. Until recently, only a small number of studies evaluating macrolides in patients with non-cystic fibrosis (CF) bronchiectasis had been published. These were open-label, uncontrolled, short-duration studies that included small numbers of patients. However, these studies suggested that macrolides can reduce exacerbation frequency, reduce sputum volume, and improve lung function in patients with non-CF bronchiectasis. Three recently published randomised, double-blind, placebo-controlled studies showed that macrolides (azithromycin or erythromycin) taken for between 6 and 12 months led to significant reductions in exacerbation rate and reduced the decline in lung function. In all studies, macrolides were generally well tolerated. The advantages of macrolide maintenance therapy need to be balanced against the risks, which include emergence of bacterial resistance, cardiotoxicity and ototoxicity. In addition, a key need is the consistent definition of endpoints for studies in non-CF bronchiectasis, particularly the definition of exacerbation, to allow systematic data analysis. Existing studies on the use of low-dose macrolides in non-CF bronchiectasis are encouraging, but further studies are needed to define the optimal agent, dose, duration for treatment, and the patients likely to benefit and long-term safety.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Erythromycin; Evidence-Based Medicine; Female; Forced Expiratory Volume; Humans; Macrolides; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiration; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Bronchiolitis; Cystic Fibrosis; Disease Progression; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive; Quality of Life

Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown.. (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects?. A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect.. Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012).. Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice.. Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Bronchiectasis; Cystic Fibrosis; Double-Blind Method; Humans; Infant, Newborn

Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis.. We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV. Cumulatively the three trials included 984 patients. Changes in FEV. Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV

Topics: Anti-Bacterial Agents; Azithromycin; Aztreonam; Bronchiectasis; Humans; Mannitol; Quality of Life

Bronchiectasis (abnormal dilatation of bronchi) is usually diagnosed by high resolution computed tomography (HRCT) and radiological severity has been found to correspond with clinical outcome. A beneficial effect of macrolides maintenance treatment in frequent exacerbating bronchiectasis patients has been established in randomized trials. This study was undertaken to prospectively evaluate the effect of long-term azithromycin (AZM) on radiological features in patients with bronchiectasis.. The BAT randomized controlled trial (2008-2010) investigated the effect of 1 year of AZM (250 mg OD) in bronchiectasis with frequent exacerbations. Chest (HR)CT-scans at baseline and after one year of study treatment were obtained and scored by two radiologists according to the Brody - and the Bhalla scoring system.. 77 (93%) patients conducted the BAT trial were evaluated in this post-hoc analysis. A significant improvement of the radiological features based on the Brody score was found after one year of AZM therapy as compared to placebo (p = 0.024), with a not significant improvement of the Bhalla score (p=0.071). Especially the consolidation (Bhalla) and parenchymal changes (Brody) sub scores significantly improved (both p=0.030), and even a radiological deterioration was seen on the Brody bronchiectasis sub score for the placebo treated patients (mean 14.5 (11.7) vs.15.7 (11.9)).. The beneficial effect of long-term AZM treatment on radiological features was demonstrated in this randomized controlled trial. (HR)CT's can be used as an objective measure of treatment response in bronchiectasis.. NCT00415350.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Humans; Macrolides; Tomography, X-Ray Computed

Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans.. A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074).. Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 μg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups.. Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis.. Cystic Fibrosis Foundation.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child; Child, Preschool; Cystic Fibrosis; Double-Blind Method; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-8; Leukocyte Elastase

Non-cystic fibrosis bronchiectasis (NCFB) brought a heavy healthcare burden worldwide. Macrolide maintenance therapy was proved to be helpful in reducing exacerbation of NCFB. However, the optimal dosing regimens of macrolides have not been determined, and its efficacy in Chinese NCFB population has not been validated. This protocol describes a head-to-head clinical trial designed to compare the efficacy of two dosing regimens of azithromycin in Chinese NCFB population.. This prospective, open-label and randomised controlled trial will be conducted in the First People's Hospital of Jiashan, China. Eligible patients with high-resolution CT defined NCFB will be randomly divided into three groups, which will receive either 250 mg daily azithromycin, or 500 mg three-times-weekly azithromycin or no treatment for 6 months. They will be followed up for another 6 months without treatment. The primary outcome is the mean rate of protocol-defined pulmonary exacerbation at 6 months.. Ethical approval was obtained from the First People's Hospital of Jiashan Ethics Committee. The findings will be disseminated in peer-reviewed publications.. ChiCTR2100052906.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Cystic Fibrosis; Fibrosis; Humans; Macrolides; Prospective Studies; Randomized Controlled Trials as Topic

Bronchiectasis guidelines recommend antibiotics for the treatment of acute respiratory exacerbations, but randomised placebo-controlled trials in children are lacking. We hypothesised that oral amoxicillin-clavulanate and azithromycin would each be superior to placebo in achieving symptom resolution of non-severe exacerbations in children by day 14 of treatment.. In this multicentre, three-arm, parallel, double-dummy, double-blind, randomised placebo-controlled trial at four paediatric centres in Australia and New Zealand, we enrolled children aged 1-18 years with CT-confirmed bronchiectasis unrelated to cystic fibrosis, who were under the care of a respiratory physician and who had had at least two respiratory exacerbations in the 18 months before study entry. Participants were allocated (1:1:1) at exacerbation onset to receive oral suspensions of amoxicillin-clavulanate (45 mg/kg per day) plus placebo azithromycin, azithromycin (5 mg/kg per day) plus placebo amoxicillin-clavulanate, or both placebos for 14 days. An independent statistician prepared a computer-generated, permuted-block (size 2-8) randomisation sequence, stratified by centre, age, and cause. Participants, caregivers, study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was the proportion of children with exacerbation resolution by day 14 in the intention-to-treat population. Treatment groups were compared using generalised linear models. Statistical significance was set at p<0·0245 to account for multiple comparisons. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000011886) and is completed.. Between April 17, 2012, and March 1, 2017, 604 children were screened and 252 were enrolled. Between July 31, 2012, and June 26, 2017, 197 children were allocated at the start of an exacerbation (63 to the amoxicillin-clavulanate group, 67 to the azithromycin group, and 67 to the placebo group). Respiratory viruses were identified in 82 (53%) of 154 children with available nasal swabs on day 1 of treatment. Primary outcome data were available for 196 (99%) children (one child with missing data [placebo group] was recorded as non-resolved according to criteria defined a priori). By day 14, exacerbations had resolved in 41 (65%) children in the amoxicillin-clavulanate group, 41 (61%) in the azithromycin group, and 29 (43%) in the placebo group. Compared with placebo, relative risk for resolution by day 14 was 1·50 (95% CI 1·08-2·09, p=0·015; number-needed-to-treat [NNT] 5 [95% CI 3-20]) in the amoxicillin-clavulanate group and 1·41 (1·01-1·97, p=0·042; NNT 6 [3-79]) in the azithromycin group. Adverse events were recorded in 19 (30%) children in the amoxicillin-clavulanate group, 20 (30%) in the azithromycin group, and 14 (21%) in the placebo group, but no events were severe or life-threatening.. Amoxicillin-clavulanate treatment is beneficial in terms of resolution of non-severe exacerbations of bronchiectasis in children, and should remain the first-line oral antibiotic in this setting.. National Health and Medical Research Council (Australia), Cure Kids (New Zealand).

Topics: Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Australia; Azithromycin; Bronchiectasis; Child; Child, Preschool; Clavulanic Acid; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lung; Male; New Zealand; Treatment Outcome

Although amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis.. We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897).. We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed non-inferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5).. By 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance.. Australian National Health and Medical Research Council.

Topics: Administration, Oral; Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; beta-Lactamase Inhibitors; Bronchiectasis; Child; Child, Preschool; Disease Progression; Double-Blind Method; Equivalence Trials as Topic; Female; Humans; Infant; Male; Time Factors; Treatment Outcome; Young Adult

Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Bacteria; Bacterial Infections; Bronchiectasis; Carrier State; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Macrolides; Male; Nasopharynx; New Zealand; Pacific Islands; Placebos; Population Groups

We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis. The objectives were to demonstrate that this treatment reduces sputum volume, improves quality of life and to assess the lengths of effects after cessation of therapy.. Seventy-eight patients with bronchiectasis confirmed by high-resolution computed tomography were included in this study. Subjects received oral azithromycin or placebo in a randomized manner for 12 weeks followed by placebo for another 12 weeks. Sputum volume, St George's Respiratory Questionnaire (SGRQ) score and spirometry were recorded at baseline, 12 weeks and 24 weeks, respectively. End-point measurements were compared from baseline to the end of each study phase.. Sixty-eight subjects were included in the analysis. Mean 24-h sputum volume significantly decreased (P < 0.01) during the active treatment phase and remained low during the control phase (P < 0.01). The mean SGRQ total score with azithromycin decreased (i.e. improved health status) from baseline by more than the 4 points at the end of 12 and 24 weeks. Lung functions remained stable during oral azithromycin therapy and the subsequent control phase.. Twelve weeks administration of azithromycin in bronchiectasis produces significant reductions in mean sputum volume, health status and stabilization of lung function values. Sputum volume reduction and the improvement of quality of life were sustained for 12 weeks after cessation of azithromycin. (Clinicaltrials.gov number NCT02107274).

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Drug Monitoring; Female; Health Status; Humans; Inflammation; Lung; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Sputum; Treatment Outcome

Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis.. This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available.. Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations.. Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clinical Protocols; Double-Blind Method; Humans; Outcome Assessment, Health Care; Sample Size

Macrolide antibiotics have been shown beneficial in cystic fibrosis (CF) and diffuse panbronchiolitis, and earlier findings also suggest a benefit in non-CF bronchiectasis.. To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis.. The BAT (Bronchiectasis and Long-term Azithromycin Treatment) study, a randomized, double-blind, placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherlands among 83 outpatients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year.. Azithromycin (250 mg daily) or placebo for 12 months.. Number of infectious exacerbations during 12 months of treatment. Secondary end points included lung function, sputum bacteriology, inflammatory markers, adverse effects, symptom scores, and quality of life.. Forty-three participants (52%) received azithromycin and 40 (48%) received placebo and were included in the modified intention-to-treat analysis. At end of study, the median number of exacerbations in the azithromycin group was 0 (interquartile range [IQR], 0-1), compared with 2 (IQR, 1-3) in the placebo group (P < .001). Thirty-two (80%) placebo-treated vs 20 (46%) azithromycin-treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95% CI, 0.16-0.51]). In a mixed-model analysis, change in forced expiratory volume in the first second of expiration (percent of predicted) over time differed between groups (F1,78.8 = 4.085, P = .047), with an increase of 1.03% per 3 months in the azithromycin group and a decrease of 0.10% per 3 months in the placebo group. Gastrointestinal adverse effects occurred in 40% of patients in the azithromycin group and in 5% in the placebo group (relative risk, 7.44 [95% CI, 0.97-56.88] for abdominal pain and 8.36 [95% CI, 1.10-63.15] for diarrhea) but without need for discontinuation of study treatment. A macrolide resistance rate of 88% was noted in azithromycin-treated individuals, compared with 26% in the placebo group.. Among adults with non-CF bronchiectasis, the daily use of azithromycin for 12 months compared with placebo resulted in a lower rate of infectious exacerbations. This could result in better quality of life and might influence survival, although effects on antibiotic resistance need to be considered.. clinicaltrials.gov Identifier: NCT00415350.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Biomarkers; Bronchiectasis; Double-Blind Method; Drug Resistance, Bacterial; Female; Humans; Inflammation; Lung; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Respiratory Tract Infections; Sputum

To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate (EBC) of adult patients with stable non-cystic fibrosis (CF) bronchiectasis.. Open-label prospective study of 30 patients randomized to azithromycin 250 mg three times per week during 3 months (16 patients) or control (14 patients). Primary outcome were changes in nitric oxide, 8-isoprostane, pH, nitrites and nitrates in EBC. Secondary outcomes were changes in exacerbation rates, dyspnoea (Borg scale), sputum volume (cc), sputum colour (15-point scale), bacterial infection, health-related quality of life (St George's Respiratory Questionnaire), lung function and radiological extension.. Azithromycin produced a significant decrease in sputum volume (8.9 (1.8) mL vs 2.1 (3.4) mL) and number of exacerbations (0.1 (0.6) vs 1.2 (0.9)). Dyspnoea (0.4 (0.1) vs 0.1 (0.2)) and health-related quality of life also improved after therapy. However, oxidative stress markers in EBC, systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy. A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients. In this subgroup, treatment was followed by a significant reduction in sputum volume, number of exacerbations, dyspnoea and St George's Respiratory Questionnaire total score. Of all airway oxidative stress markers, only nitrates in EBC were reduced after therapy.. Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis, but it does not affect airway oxidative stress markers.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Biomarkers; Bronchiectasis; Dinoprost; Female; Follow-Up Studies; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Prospective Studies; Treatment Outcome

Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease.. Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1-2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.. 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention.. Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.. National Health and Medical Research Council (Australia) and Health Research Council (New Zealand).

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Bronchiectasis; Carrier State; Child; Child, Preschool; Chronic Disease; Disease Progression; Double-Blind Method; Drug Resistance, Bacterial; Early Termination of Clinical Trials; Episode of Care; Female; Haemophilus influenzae; Humans; Infant; Intention to Treat Analysis; Length of Stay; Lung Diseases; Male; Microbial Sensitivity Tests; Moraxella catarrhalis; Native Hawaiian or Other Pacific Islander; Nose; Severity of Illness Index; Staphylococcus aureus; Streptococcus pneumoniae; Suppuration; Time Factors

The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis.. We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12-24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV(1); for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms.. Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children.. Australian New Zealand Clinical Trials Registry: ACTRN12610000383066.

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Bronchiectasis; Child; Child, Preschool; Clinical Protocols; Disease Progression; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Humans; Infant; Intention to Treat Analysis; Kaplan-Meier Estimate; Native Hawaiian or Other Pacific Islander; New Zealand; Proportional Hazards Models; Treatment Outcome

Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis.. We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493.. 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108).. Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year.. Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Cystic Fibrosis; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Quality of Life; Secondary Prevention; Treatment Outcome; Vital Capacity

Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis.. We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported.. Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.. Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.

Topics: Administration, Oral; Adolescent; Age Factors; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Australia; Azithromycin; Bronchiectasis; Child; Child, Preschool; Disease Progression; Double-Blind Method; Hospitalization; Humans; Infant; Infant, Newborn; New Zealand; Quality of Life; Research Design; Time Factors; Treatment Outcome

Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation. We investigated whether the addition of 6-months' twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin.. Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited. In random order, patients received usual medications for 6 months, and usual medications plus oral azithromycin 500mg twice weekly for 6 months. Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase. Patients recorded weekly peak flow (PF) measurements. Pulmonary function tests (PFTs), 24-hour sputum volume, and needs for intervention with medication or ancillary support were collected at baseline and every 3 months. Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase.. Twelve patients were enrolled; 11 were included in the analysis. Owing to randomization, most patients received the azithromycin first, which was fairly well tolerated. PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase. Azithromycin significantly decreased the incidence of exacerbations compared with usual medications (5 vs 16; p = 0.019). Mean 24-hour sputum volume significantly decreased (15% [p = 0.005]) during the active treatment phase, and remained decreased during the control phase (p = 0.028). Subjectively, patients reported increased energy and quality of life while receiving treatment with azithromycin.. The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study. The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Cross-Over Studies; Humans; Pilot Projects; Respiratory Function Tests; Sputum

Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population. Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis. In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life. We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome. To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks). In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy. The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Bronchiolitis Obliterans; Cystic Fibrosis; Drug Administration Schedule; Follow-Up Studies; Forced Expiratory Volume; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Pilot Projects; Pulmonary Fibrosis; Quality of Life; Severity of Illness Index; Syndrome; Time Factors; Treatment Outcome

Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity.. During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants.. At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV. One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchi; Bronchiectasis; Humans; Inflammation; Interleukin-1; Macrolides; Sputum; Tumor Necrosis Factor-alpha

The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention.. NTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis.. 135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and. The incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.

Topics: Antitubercular Agents; Azithromycin; Bronchiectasis; Follow-Up Studies; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Tertiary Care Centers

Low-dose long-term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OAD); however, an optimal therapeutic regimen is not yet established.. To understand the patterns of azithromycin use in OAD, characterise the patients who received it and evaluate its safety and efficacy using real-world data.. We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non-cystic fibrosis bronchiectasis.. The mean age was 65 ± 18 years, 60% were female and 48% were ex-smokers. The majority had asthma (75%), either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250 mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% vs 32%; P < 0.001) and hospital admissions (35% vs 31%; P < 0.001) after starting azithromycin. In 88% of cases, physicians favoured the use of azithromycin.. Physicians are currently using low-dose azithromycin for a long duration of more than 1 year for the management of OAD. The typical case definition is an older non-smoking adult with persistent asthma, often in combination with another OAD and presenting with bothersome cough or sputum. Azithromycin was well tolerated and led to reduced healthcare utilisation. Further research is required to establish an optimal dosage regimen of azithromycin in OAD.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Cough; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

To explore the clinical benefits of azithromycin in the treatment of Pseudomonas aeruginosa induced bronchiectasis and to evaluate its effect on MUC5AC. From April 2018 to June 2020, 160 patients with bronchiectasis due to Pseudomonas aeruginosa infection were selected. The patients were divided into a control groupand an azithromycin group. Statistics of patients' general clinical data, lung function indexes, sputum volume, oxidative stress level, Bhalla score before and after treatment; Western blot analysis of MUC5AC expression; RT-PCR analysis of TNF-α, IL-8, IL- 1β mRNA expression. The mRNA expression of TNF-α, IL-8 and IL-1β in the azithromycin group was lower than that in the control group (P<0.05). After treatment, the protein expression of MUC5AC in the azithromycin group was lower than that in the control group (P<0.05). The improvement rate in the azithromycin group was significantly higher than that in the control group (P<0.05). The azithromycin group had a lower lung infection rate than the control group (P<0.05). The azithromycin group had a lower dyspnea rate than the control group (P<0.05). Azithromycin treatment has certain clinical benefits for patients with bronchiectasis induced by Pseudomonas aeruginosa and inhibits the MUC5AC expression.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Dyspnea; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Mucin 5AC; Pseudomonas aeruginosa; Pseudomonas Infections; RNA, Messenger; Tumor Necrosis Factor-alpha

Topics: Australia; Azithromycin; Bronchiectasis; Child; Humans

Bronchiectasis is predominantly a neutrophilic inflammatory disease. There are no established therapies that directly target neutrophilic inflammation because little is understood of the underlying mechanisms leading to severe disease. Neutrophil extracellular trap (NET) formation is a method of host defence that has been implicated in multiple inflammatory diseases. We aimed to investigate the role of NETs in disease severity and treatment response in bronchiectasis.. In this observational study, we did a series of UK and international studies to investigate the role of NETs in disease severity and treatment response in bronchiectasis. First, we used liquid chromatography-tandem mass spectrometry to identify proteomic biomarkers associated with disease severity, defined using the bronchiectasis severity index, in patients with bronchiectasis (n=40) in Dundee, UK. Second, we validated these biomarkers in two cohorts of patients with bronchiectasis, the first comprising 175 patients from the TAYBRIDGE study in the UK and the second comprising 275 patients from the BRIDGE cohort study from centres in Italy, Spain, and UK, using an immunoassay to measure NETs. Third, we investigated whether pathogenic bacteria had a role in NET concentrations in patients with severe bronchiectasis. In a separate study, we enrolled patients with acute exacerbations of bronchiectasis (n=20) in Dundee, treated with intravenous antibiotics for 14 days and proteomics were used to identify proteins associated with treatment response. Findings from this cohort were validated in an independent cohort of patients who were admitted to the same hospital (n=20). Fourth, to assess the potential use of macrolides to reduce NETs in patients with bronchiectasis, we examined two studies of long-term macrolide treatment, one in patients with bronchiectasis (n=52 from the UK) in which patients were given 250 mg of azithromycin three times a week for a year, and a post-hoc analysis of the Australian AMAZES trial in patients with asthma (n=47) who were given 500 mg of azithromycin 3 times per week for a year.. Sputum proteomics identified that NET-associated proteins were the most abundant and were the proteins most strongly associated with disease severity. This finding was validated in two observational cohorts, in which sputum NETs were associated with bronchiectasis severity index, quality of life, future risk of hospital admission, and mortality. In a subgroup of 20 patients with acute exacerbations, clinical response to intravenous antibiotic treatment was associated with successfully reducing NETs in sputum. Patients with Pseudomonas aeruginosa infection had a lessened proteomic and clinical response to intravenous antibiotic treatment compared with those without Pseudomonas infections, but responded to macrolide therapy. Treatment with low dose azithromycin was associated with a significant reduction in NETs in sputum over 12 months in both bronchiectasis and asthma.. We identified NETs as a key marker of disease severity and treatment response in bronchiectasis. These data support the concept of targeting neutrophilic inflammation with existing and novel therapies.. Scottish Government, British Lung Foundation, and European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC).

Topics: Anti-Bacterial Agents; Azithromycin; Biomarkers; Bronchiectasis; Cohort Studies; Extracellular Traps; Humans; Macrolides; Proteomics; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Function Tests; Severity of Illness Index; Sputum

Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.

Topics: Adult; Arthritis, Juvenile; Azithromycin; Bronchiectasis; Cell Proliferation; Cells, Cultured; Child; Ectodermal Dysplasia; Gain of Function Mutation; Gentamicins; Humans; Immunologic Deficiency Syndromes; Leukocytes, Mononuclear; Male; Meningitis, Bacterial; Neisseria meningitidis; NF-KappaB Inhibitor alpha; Papillomaviridae; Pedigree; Pseudomonas aeruginosa; Pseudomonas Infections; Virus Diseases; Warts; Young Adult

OBJECTIVES To evaluate the efficacy of mucosal bacterial vaccines (MBV) in reducing the number of exacerbations in patients with chronic respiratory disease. METHODS A prospective cohort study of patients followed at the Pneumology Unit of the University and Hospital Centre of Coimbra, with frequent infectious exacerbations (3 or more) despite the best therapeutic strategies employed. MBV was used as additional therapy. The number of exacerbations 1 year before therapy and 1 year after it were analyzed. RESULTS A sample of 11 individuals, 45.5% male, mean age 62.5 years. Eight patients had non-cystic fibrosis bronchiectasis, 2 COPD (1 on long-term oxygen therapy), and 1 patient with Mounier Kuhn's syndrome. Three patients were on azithromycin, 1 on inhaled colistin, and 2 on inhaled tobramycin. Out of the 11 patients, one presented complication (fever), which led to a suspension of therapy (excluded from results). Of the 10 patients who completed treatment, 5 had bacterial colonization and were submitted to a custom vaccine. The remaining 6 completed the standard composition. The average of infectious exacerbations in the previous year was 4.3 (0.7 with hospitalization). In the year after therapy, the mean number was 1.5 (0.5 with hospitalization). CONCLUSION The results obtained in this study favor the use of bacterial immunostimulation to reduce the frequency of RRIs in patients with chronic respiratory disease.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Vaccines; Bronchiectasis; Colistin; Female; Humans; Male; Middle Aged; Prospective Studies

Topics: Amoxicillin; Azithromycin; Bronchiectasis; Child; Clavulanic Acid; Double-Blind Method; Fibrosis; Humans

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Belgium; Bronchiectasis; Disease Progression; Enterobacteriaceae; Female; Guideline Adherence; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Patient Care Planning; Patient Care Team; Patient Education as Topic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pseudomonas aeruginosa; Pulmonary Medicine; Self Care; Sputum; Surveys and Questionnaires

Bronchiectasis results when inflammatory and infectious damage to the bronchial and bronchiolar walls leads to a vicious cycle of airway injury. On the basis of the classic characteristic, that is, permanent bronchial dilatation, bronchiectasis is generally considered irreversible in the adult population.. A 21-year-old woman presented to our hospital with a 9-day history of productive cough and fever.. Bronchiectasis after Mycoplasma pneumoniae pneumonia.. The patient was treated with azithromycin for 7 days.. The bronchial dilatation resolved as evidenced by sequential chest high-resolution computed tomography 7 days and 1 month later, respectively.. Although complete disappearance is quite rare in adult, this case demonstrated that bronchial dilatation might resolve completely in such a fascinating short period of time if receiving adequate and timely regimens.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Female; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Chronic Disease; Contraindications, Drug; Disease Progression; Humans; Time Factors

Macrolides antibiotics have been effectively used in many chronic diseases, especially with

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Cells, Cultured; Humans; Inflammasomes; Macrolides; Macrophages; Mice; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Bronchiolitis; Bronchiolitis Obliterans; Haemophilus Infections; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections

A series of co-engineered macrolide-mannitol particles were successfully prepared using azithromycin (AZ) as a model drug. The formulation was designed to target local inflammation and bacterial colonization, via the macrolide component, while the mannitol acted as mucolytic and taste-masking agent. The engineered particles were evaluated in terms of their physico-chemical properties and aerosol performance when delivered via a novel high-payload dry powder Orbital(™) inhaler device that operates via multiple inhalation manoeuvres. All formulations prepared were of suitable size for inhalation drug delivery and contained a mixture of amorphous AZ with crystalline mannitol. A co-spray dried formulation containing 200 mg of 50:50 w/w AZ: mannitol had 57.6% ± 7.6% delivery efficiency with a fine particle fraction (≤6.8 µm) of the emitted aerosol cloud being 80.4% ± 1.1%, with minimal throat deposition (5.3 ± 0.9%). Subsequently, it can be concluded that the use of this device in combination with the co-engineered macrolide-mannitol therapy may provide a means of treating bronchiectasis.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Chemistry, Pharmaceutical; Drug Delivery Systems; Dry Powder Inhalers; Excipients; Mannitol; Particle Size; Powders

There is no large study validating the appropriateness of current treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is a retrospective single-center review evaluating the efficacy of macrolide/azalide-containing regimens for nodular/bronchiectatic (NB) MAC lung disease.. Patients were treated according to contemporary guidelines with evaluation of microbiologic responses. Macrolide susceptibility of MAC isolates was done at initiation of therapy, 6 to 12 months during therapy, and on the first microbiologic recurrence isolate. Microbiologic recurrence isolates also underwent genotyping for comparison with the original isolates.. One hundred eighty patients completed > 12 months of macrolide/azalide multidrug therapy. Sputum conversion to culture negative occurred in 154 of 180 patients (86%). There were no differences in response between clarithromycin or azithromycin regimens. Treatment regimen modification occurred more frequently with daily (24 of 30 [80%]) vs intermittent (2 of 180 [1%]) therapy (P = .0001). No patient developed macrolide resistance during treatment. Microbiologic recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC isolates, 27% with true relapse isolates (P = .03). Overall, treatment success (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after completion of therapy: 75% reinfection isolates, 25% true relapse isolates.. Current guidelines for macrolide/azalide-based therapies for NB MAC lung disease result in favorable microbiologic outcomes for most patients without promotion of macrolide resistance. Intermittent therapy is effective and significantly better tolerated than daily therapy. Microbiologic recurrences during or after therapy are common and most often due to reinfection MAC genotypes.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Follow-Up Studies; Genotype; Humans; Lung Diseases; Macrolides; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Practice Guidelines as Topic; Recurrence; Retrospective Studies; Sputum; Treatment Outcome

Topics: Azithromycin; Bronchiectasis; Clarithromycin; Female; Humans; Lung Diseases; Macrolides; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchiectasis; Erythromycin; Female; Humans; Male; Respiratory Tract Infections

Topics: Azithromycin; Bronchiectasis; Female; Humans; Male; Oxidative Stress

Existing literature is inconclusive regarding how the nodular bronchiectatic form of Mycobacterium avium complex (MAC) disease will progress without treatment and when treatment initiation should be considered.. To assess the natural course of MAC pulmonary disease by serial thin-section computed tomography (CT).. Of 339 patients with nodular bronchiectatic form of MAC disease, we selected 265 untreated patients who had serial CTs (mean observation period, 32 ± 21 mo). Two independent chest radiologists reviewed retrospectively all CT scans for the presence and extent of lung abnormalities (maximal total score, 30).. Of 265 patients, 126 patients (48%) had disease that had progressed and that needed treatment owing to radiologic deterioration or worsening symptoms, and the remaining 139 patients (52%) did not. On multivariate analysis, the presence of cavity (adjusted hazard ratio, 2.06; P = 0.004) and consolidation (adjusted hazard ratio, 1.55; P = 0.019) at initial CT remained as independent factors associated with disease progression and treatment requirement. The presence of cavitary lesions demonstrated the highest positive predictive value (61%) and significant correlation (P = 0.005) with smear positivity. Differences in the extent of each pattern and total CT score in the serial studies were significantly larger (P < 0.05) in patients requiring treatment. The total CT score increased by 2.41 in the treatment-requiring group compared with 0.25 in the group that did not receive treatment.. Without treatment, about half of patients demonstrate progressive disease on serial CT over a mean follow-up period of 32 months and, thus, required treatment. Patients showing cavities or consolidation on initial CT are more likely to have progressive disease and thus to require treatment eventually.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; Disease Progression; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung; Male; Middle Aged; Multiple Pulmonary Nodules; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Proportional Hazards Models; Retrospective Studies; Rifampin; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Carrier State; Female; Humans; Lung Diseases; Male; Native Hawaiian or Other Pacific Islander

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Female; Humans; Male

Previous studies have demonstrated that long-term low-dose macrolides are efficacious in cystic fibrosis (CF) and diffuse panbronchiolitis, two chronic neutrophilic airway diseases.. The aims of this study were to evaluate the efficacy and safety of low-dose neomacrolides as add-on therapy in patients with severe asthma and/or bronchiectasis and to identify predictors for therapeutic response.. In a retrospective observational cohort study, we examined 131 adult, non-CF patients with severe asthma and/or bronchiectasis, receiving low-dose neomacrolides as add-on treatment. Pulmonary function tests and symptom scores were assessed at baseline and after 3 to 8 weeks of therapy.. After 3-8 weeks of treatment with low-dose neomacrolides, 108 patients were available for evaluation. In asthma patients (n = 47), pulmonary function tests and symptom scores improved significantly. Responders (≥7% forced expiratory volume in one second predicted [FEV(1)%] improvement) were older (55 vs. 47 years; p = 0.042) and had a longer duration of asthma (29 vs. 9 years; p = 0.052). In patients with bronchiectasis only (n = 61), symptom scores improved significantly. Responders (≥60% symptom score improvement) were older (61 vs. 53 years; p = 0.004), more frequently male (53% vs. 27%; p = 0.043), and there was a nonsignificant trend towards higher high-resolution CT (HRCT) score for bronchiectasis in responders (6.4 vs. 4.6; p = 0.053). In multivariate logistic regression analysis, age and male gender were independent predictors for improvement in this group.. The results of this retrospective study suggest that neomacrolides may be useful as an add-on therapy in patients with severe asthma and/or bronchiectasis. Older age may predict good response in patients with severe asthma, whereas older age, male gender and a higher HRCT score for bronchiectasis may predict therapeutic response in patients with bronchiectasis only. Prospective controlled trials of neomacrolides in patients with severe asthma are needed to confirm these observations.

Topics: Adult; Age Factors; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchiectasis; Clarithromycin; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Respiratory Function Tests; Retrospective Studies; Severity of Illness Index; Sex Factors; Treatment Outcome

We describe our institutional efficacy experience of azithromycin 250 mg thrice weekly in adult non-cystic fibrosis bronchiectasis.. Eligibility criteria for prophylactic azithromycin included 3 exacerbations requiring rescue antibiotics over the previous 6 months. The clinical records of 56 bronchiectasis patients on azithromycin were retrospectively reviewed. Exacerbation frequency, sputum microbiology, self-reported change in sputum volume, and spirometry results were recorded.. Mean length of treatment was 9.1 months (7.5) and 50 patients had treatment > or = 3 months. Spirometry, pre- and post-azithromycin in 29 patients, who had 3 or more months of treatment, showed a mean increase in FEV(1) of 83 ml (0.14) (P=0.005) from 1.560 to 1.643l. There was a decrease in the exacerbation frequency from 0.81/month (SD) (0.32) pre-azithromycin to 0.41/month (0.45) (P<0.001) post-azithromycin. Clinically significant suppression of previous sputum microbial isolates was also observed.. Azithromycin improves exacerbation frequency, spirometry, and sputum microbiology in bronchiectasis.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Drug Administration Schedule; Female; Humans; Lung; Male; Middle Aged; Respiratory Function Tests; Retrospective Studies; Sputum; Treatment Outcome

Topics: Anti-Infective Agents; Azithromycin; Bronchiectasis; Female; Humans; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

Azithromycin has been shown to be beneficial in several diseases with chronic neutrophilic inflammation of the airways, such as cystic fibrosis and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now, however, its healing effect on bronchiectasis has never been demonstrated. We report a heart-lung transplant patient who developed chronic rejection (BOS stage 3) with the appearance of gross bronchiectasis on a spiral computed tomography (CT) chest scan. Within 2 weeks after starting azithromycin, the patient's forced expiratory volume in 1 second increased significantly and a repeat spiral CT chest scan 5 months later, showed a major improvement of the bronchiectasis. This case report illustrates that bronchiectasis may greatly improve after treatment with azithromycin and no longer needs to be considered an endstage finding in patients with severe BOS.

Topics: Adolescent; Azithromycin; Bronchiectasis; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Eisenmenger Complex; Female; Follow-Up Studies; Graft Rejection; Heart-Lung Transplantation; Humans; Oxygen Consumption; Pulmonary Gas Exchange; Radiography; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Transplantation, Homologous; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bronchiectasis; Female; Humans; Male; Middle Aged

The genomic DNA patterns (genotypes) of 55 episodes of late positive sputum isolates, collected after >or=4 consecutive months of negative sputum cultures, in prospective macrolide treatment trials of Mycobacterium avium complex (MAC) lung disease were assessed by pulsed-field gel electrophoresis (PFGE). Having >or=2 cultures positive for MAC after completion of therapy was documented 23 times; of 20 episodes studied by PFGE, 17 (85%) represented new genotypes (i.e., new infections), and 87% occurred in patients with nodular bronchiectasis. With >or=2 positive cultures after therapy was stopped prematurely, 6 (86%) of 7 episodes were relapses. Single positive cultures after completion of therapy occurred 16 times; only 1 (6%) was predictive of a subsequent relapse. No late isolates were macrolide resistant. Thus, relapses of MAC lung disease with these macrolide regimens are unusual, and most infections after completing therapy resulted from new strains in patients with nodular bronchiectasis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Polymerase Chain Reaction; Prospective Studies; Sputum