zithromax and Lung-Diseases

Treatment of

Topics: Aged; Amikacin; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Databases, Factual; Female; Humans; Imipenem; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous

In health, the glucose concentration of airway surface liquid (ASL) is 0.4 mM, about 12 times lower than the blood glucose concentration. Airway glucose homeostasis comprises a set of processes that actively maintain low ASL glucose concentration against the transepithelial gradient. Tight junctions between airway epithelial cells restrict paracellular glucose movement. Epithelial cellular glucose transport and metabolism removes glucose from ASL. Low ASL glucose concentrations make an important contribution to airway defense against infection, limiting bacterial growth by restricting nutrient availability. Both airway inflammation, which increases glucose permeability of tight junctions, and hyperglycemia, which increases the transepithelial glucose gradient, increase ASL glucose concentrations, with the greatest effect seen where they coexist. Elevated ASL glucose drives proliferation of bacteria able to use glucose as a carbon source, including Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacteria. Clinically, this appears to be important in driving exacerbations of chronic lung disease, especially in patients with comorbid diabetes mellitus. Drugs can restore airway glucose homeostasis by reducing the permeability of tight junctions (eg, metformin), increasing epithelial cell glucose transport (eg, β-agonists, insulin), and/or by lowering blood glucose (eg, dapagliflozin). In cell culture and animal models these reduce ASL glucose concentrations and limit bacterial growth, preventing infection. Observational studies in humans indicate that airway glucose homeostasis-modifying drugs could prevent chronic lung disease exacerbations if tested in randomized trials.

Topics: Adrenergic beta-Agonists; Animals; Azithromycin; Glucocorticoids; Glucose; Humans; Hypoglycemic Agents; Lung Diseases; PPAR gamma; Respiratory Mucosa; Respiratory Tract Infections; Tight Junctions; Vitamin D

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary condition, characterized by diffuse proliferation of neuroendocrine cells in the respiratory epithelium. DIPNECH lesions are less than 5 mm in size and are limited to the basement membrane with no invasion. There is limited information regarding epidemiology, natural history of disease progression, or the management of this rare entity. We present the experience of a center with extensive expertise in neuroendocrine disease.. A cohort of patients (N = 13) with DIPNECH treated and followed at our institution was identified. We describe the our approach to their care, our disease management and also provide a review of DIPNECH pathophysiology.. Our patient cohort consisted of twelve females and one male with a mean age of 63 years at the time of diagnosis. Dyspnea on exertion and dry cough were the most common presenting symptoms. Two patients were under surveillance without treatment; three patients were treated with a short-acting somatostatin analog; three patients were treated with azithromycin alone; four were treated with a combination of long-acting monthly somatostatin analogs and azithromycin; one patient received a combination of long-acting somatostatin analog and everolimus. Five patients had concomitant bronchial carcinoids.. DIPNECH is a rare pathology that can profoundly affect a patient's quality of life. Paroxysmal coughing episodes can be difficult to treat. Our limited single center experience shows encouraging response to use of somatostatin analogs, azithromycin, and everolimus in the management of debilitating DIPNECH associated symptoms.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Agents, Hormonal; Azithromycin; Bronchial Neoplasms; Carcinoid Tumor; Cough; Dyspnea; Everolimus; Female; Humans; Hyperplasia; Immunosuppressive Agents; Lung Diseases; Male; Middle Aged; Multiple Pulmonary Nodules; Neuroendocrine Cells; Octreotide; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Quality of Life; Respiratory Mucosa

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

Azithromycin has a well-characterized bacteriostatic activity. However, it also has a robust immunomodulatory effect that has proven beneficial in a variety of chronic illnesses. This effect results in decreased production of pro-inflammatory cytokines in the acute phase and promotes resolution of chronic inflammation in the later phases. Specifically, azithromycin has direct activity on airway epithelial cells to maintain their function and reduce mucus secretion. These characteristics have resulted in the use of azithromycin in the management of a variety of chronic lung diseases including chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis, bronchiolitis obliterans syndrome, diffuse panbronchiolitis, and asthma. In this review, we present the evidence supporting the role of azithromycin in these conditions with an emphasis on the clinical aspects for the practicing physician.

Topics: Anti-Bacterial Agents; Azithromycin; Cytokines; Drug Resistance, Bacterial; Epithelial Cells; Humans; Immunomodulation; Inflammation; Lung Diseases

Macrolide agents have both antibacterial properties as well as various effects on the inflammatory system. In recent years there is growing evidence regarding the favourable effects of macrolides in a range of chronic respiratory conditions. Historically, erythromycin and clarithromycin were found to stabilize pulmonary deterioration in diffuse panbronchiolitis. In cystic fibrosis patients colonized with pseudomonas aeruginosa, long term treatment with azithromycin reduces exacerbations and presents improved lung function. A similar effect on prevention of exacerbations has been demonstrated in noncystic fibrosis bronchiectasis. In patients undergoing lung transplantation, long term azithromycin prevents bronchiolitis obliterans syndrome. In patients with chronic obstructive pulmonary disease (COPD), azithromycin prevents acute exacerbations. Chronic treatment with macrolides is associated with adverse effects including gastrointestinal symptoms, interactions with other drugs and cardiovascular complications. Of the macrolides, azithromycin is associated with the lowest interactions and adverse effects and is also the most investigated.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Erythromycin; Humans; Lung Diseases; Macrolides

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

Topics: Azithromycin; Chronic Disease; Humans; Lung Diseases

Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.

Topics: Azithromycin; Bronchiolitis Obliterans; Gastroesophageal Reflux; Gram-Negative Bacterial Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Diseases; Lung Transplantation; Pneumonia; Pneumonia, Aspiration; Transplantation, Homologous

Several experimental models have been used in order to evaluate the in vivo efficacy of azithromycin against numerous human pathogenic bacteria and parasites, including comparison between azithromycin and other antibiotics belonging or not to the macrolide family. Using the experimental models, three major objectives can be distinguished: the comparative studies of the efficacy dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the azithromycin efficacy in animal infected with intracellular multiplying micro-organisms, and the demonstration of the specific azithromycin accumulation in tissues in direct relationship with the local recruitment of phagocytic cells at the infectious foci. The ED50 of azithromycin has been compared with those of erythromycin or cefaclor in varying acute murine infections. Evidence was given of a similar efficacy for the three tested antibiotics. Nevertheless a marked advantage for azithromycin was observed in experimental local infections and with infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella catarrhalis). The second objective was to confirm in vivo the preferential efficacy of azithromycin in models using intracellular multiplying microorganisms, due to its great capacity to accumulate inside of professional phagocytes. Several models have been used, such as those performed with Listeria monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M. avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cefaclor; Disease Models, Animal; Erythromycin; Legionnaires' Disease; Listeriosis; Lung Diseases; Mice; Mycobacterium avium; Parasitemia; Salmonella Infections, Animal; Tuberculosis

HIV-associated immune activation contributes to chronic lung disease (CLD) in children and adolescents living with HIV. Azithromycin has immunomodulatory and anti-microbial properties that may be useful for treating HIV-associated CLD (HCLD). This study describes the effect of azithromycin on expression of plasma soluble biomarkers in children and adolescents with HCLD.. This study was nested within a multi-site double-blind, placebo controlled, randomised controlled trial (RCT) of azithromycin in individuals aged 6-19 years with HCLD (defined as FEV1 z-score < -1) in Malawi and Zimbabwe (BREATHE (NCT02426112)). Participants were randomized 1:1 to once-weekly oral azithromycin with weight-based dosing, for 48 weeks, or placebo. Twenty-six plasma soluble biomarkers were measured on a MagPix Luminex instrument at enrolment, after 48-weeks of treatment and 24-weeks after treatment cessation. Mixed effects models were constructed to compare biomarker expression across treatment and placebo groups.. Weekly azithromycin was associated with reduced levels of C-Reactive Protein (CRP), E-Selectin, Matrix metalloproteinase 10 (MMP-10). Treatment effects for all soluble biomarkers were not sustained 24-weeks after treatment cessation with biomarker expression returning to pre-treatment levels.. We observed real-world effects of azithromycin on acute inflammation, neutrophil accumulation, and extracellular matrix degradation, that were not sustained after treatment cessation. These results are pertinent when using azithromycin for its immunomodulatory properties, or targeting pathways represented by the soluble biomarkers in this study.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Biomarkers; Child; Double-Blind Method; HIV Infections; Humans; Lung Diseases

Management of co-morbidities among persons living with HIV is an emerging priority, which may require additional medication over and above life-long antiretroviral therapy (ART). We explored factors associated with adherence to the trial drug among children and adolescents with perinatally acquired HIV taking antiretroviral therapy (ART) in the Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-Infected Children (BREATHE) trial.. The BREATHE trial recruited 6-19 year olds with perinatally acquired HIV and co-morbid chronic lung disease as measured by FEV1. This two-site trial was individually randomised (1:1), double-blind and placebo-controlled. Participants received a once-weekly weight-based dose of 1-5 tablets of azithromycin (AZM: 250mg) or placebo, taken orally. We used pharmacy dispensing records and count of returned pills to measure adherence to study medication. Logistic regression was used to explore factors associated with adherence coverage. Poisson regression with Lexis expansion for time was used to explore whether adherence modified the effect of azithromycin on the incidence of acute respiratory exacerbation, a secondary outcome of the trial. Trial registration: ClinicalTrials.gov NCT02426112.. The 347 participants (median age 15.3, 51% male) consumed 14,622 doses of study medication over 16,220 person-weeks under study. Adherence was higher for those randomised to AZM (73.4%) than placebo (68.4%) and declined over the 48 weeks of the study (Score test for trend <0.02). Those with unsuppressed HIV viral load at baseline had 2.08 (95% CI: 1.19, 3.63) times the odds of non-adherence than those with viral suppression. Differences were also observed between trial sites.. The majority of children and adolescents tolerated the addition of a once-weekly dose of medication to their pill burden. Barriers in adhering to treatment for co-morbid conditions are likely common to barriers in adhering to ART. Control of co-morbidities will therefore present additional challenges in HIV care.

Topics: Adolescent; Anti-HIV Agents; Azithromycin; Child; Female; HIV Infections; Humans; Lung Diseases; Male; Medication Adherence; Viral Load

The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described.. A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks' gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks' postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks' PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up.. Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect.. We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment.. ISRCTN registry ISRCTN11650227. Registered on 31 July 2018.

Topics: Azithromycin; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Lung Diseases

Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by. Ethics permission has been granted by Wales Research Ethics Committee 2 (Ref 18/WA/0199), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (Clinical Trials Authorisation reference 21323/0050/001-0001). The study is registered on ISRCTN (ISRCTN11650227). The study is overseen by an independent Data Monitoring Committee and an independent Trial Steering Committee. We shall disseminate our findings via national and international peer-reviewed journals, and conferences. A summary of the findings will also be posted on the trial website.

Topics: Azithromycin; Child; Chronic Disease; Dexamethasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Randomized Controlled Trials as Topic; Wales

Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.. We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV. The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world's HIV-infected children live and where HIV-associated CLD is highly prevalent.. ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Chronic Disease; Data Analysis; Double-Blind Method; HIV Infections; Humans; Lung Diseases; Outcome Assessment, Health Care; Placebos; Randomized Controlled Trials as Topic; Sample Size; Young Adult

Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade.. A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3-6 months during two respiratory syncytial virus (RSV) seasons (2015-2016 and 2016-2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach.. We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters.. This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published.. NCT02544984.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chronic Disease; Clinical Protocols; Double-Blind Method; Female; Humans; Infant; Lung Diseases; Macrolides; Male; Pre-Exposure Prophylaxis; Quality of Life; Respiratory Tract Infections; Texas; Treatment Outcome

Azithromycin decreases airway neutrophilia and can prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). It also can be used to treat lymphocytic bronchiolitis, as it decreases the submucosal infiltrating IL-17 positive lymphocytes. Some patients, while receiving azithromycin, (re)develop increased airway neutrophilia, which we hypothesize to result in worse outcome and to be regulated by an IL-17-independent mechanism.. LTx recipients, transplanted between 2001 and 2012, were investigated and categorized in a study group of patients with increased broncho-alveolar lavage (BAL) neutrophilia (≥15%) and a matched control group with low BAL neutrophilia (<15%), both groups while already being on azithromycin treatment. CLAD-free and overall survival were compared between groups. Cell differentials and 33 proteins in BAL were analyzed to identify underlying mechanisms.. The study group (n=72) demonstrated a significantly lower CLAD-free (p=0.015) and overall survival (p=0.041) compared to the control group (n=37). Absolute BAL neutrophils and eosinophils were increased in the study group, which was paralleled by elevated inflammatory cytokines (IL-1β/IL-1Ra, IL-4 and IL-6) and chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL11/eotaxin) concentrations compared to the control group (all p<0.05).. Patients with elevated airway neutrophilia despite azithromycin, experience worse CLAD-free and overall survival. In these patients, IL-1β might play a central role giving rise to neutrophils, eosinophils, macrophages and B-cells. This provides an opportunity to further investigate the modulation of this pathway.

Topics: Azithromycin; Bronchoalveolar Lavage Fluid; Cytokines; Disease-Free Survival; Female; Humans; Leukocyte Disorders; Lung Diseases; Lung Transplantation; Male; Middle Aged; Survival Rate

Current definitions of pulmonary exacerbation (PE) in cystic fibrosis are based on studies in participants with significant lung disease and may not reflect the spectrum of findings observed in younger patients with early lung disease.. We used data from a recent trial assessing the efficacy of azithromycin in children to study signs and symptoms associated with PEs and related changes in lung function and weight.. While increased cough was present in all PEs, acute weight loss and reduction in oxygen saturation were not observed. Changes in lung function did not differ between subjects who did experience a PE and those who were exacerbation-free.. Cough was the predominant symptom in CF patients with early lung disease experiencing a PE. There was no significant difference in mean 6-month change in lung function or weight among subjects with one or more exacerbations and those without an exacerbation.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Cough; Cystic Fibrosis; Disease Progression; Double-Blind Method; Female; Humans; Lung; Lung Diseases; Male; Middle Aged; Respiratory Function Tests; Respiratory Tract Infections

In a chronic disease setting such as cystic fibrosis (CF), antibiotics are often prescribed for emergent symptoms and it is unclear whether this affects endpoints in a clinical trial. Pulmonary exacerbations (PEs) are defined episodes of acute worsening and a key clinical efficacy measure in CF. Our hypothesis was that acute antibiotics given for illnesses not meeting the PE definition may alter estimates of treatment effect that do not account for this antibiotic use.. A randomized, placebo-controlled trial of azithromycin (AZ) including 260 participants with CF was utilized for this study. PEs were defined using a priori criteria. Physician initiated antibiotic therapy (PIT) not meeting the PE endpoint was characterized and its impact on treatment effect assessed.. 40% (104/260) of participants were prescribed 188 courses of PIT in the absence of a PE; 19% (25/129) of placebo and 10% (13/131) of AZ participants received ≥2 courses of PIT and never fulfilled the PE definition (9% difference, 95% confidence interval: 1%, 18%, p = 0.04). Accounting for PIT through use of a composite endpoint including time to PE or need for repeated PIT altered treatment effect estimates (a 56% reduction in the event rate comparing AZ to placebo [p < 0.0001] as compared to a 50% reduction not accounting for PIT [p = 0.003]).. PIT is common in CF and may impact treatment effect estimates. Optimization of the PE endpoint to include meaningful events necessitating treatment may improve our ability to conduct efficient trials by reducing the sample size 30-50%, ultimately enabling rapid evaluation of new therapies.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Clinical Protocols; Cystic Fibrosis; Female; Humans; Lung Diseases; Male; Research Design; Sample Size

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

Two consecutive, open, prospective trials of intermittent azithromycin (600 mg), usually given Monday, Wednesday, and Friday (TIW) for Mycobacterium avium complex (MAC) lung disease were initiated in human immunodeficiency virus-negative patients. Regimen A consisted of TIW azithromycin and daily ethambutol (15 mg/kg/day), daily rifabutin (300 mg/day), and initial twice weekly (BIW) streptomycin. Regimen B consisted of TIW azithromycin, TIW ethambutol (25 mg/kg/dose), TIW rifabutin (600 mg/dose), and initial BIW streptomycin. Of 19 patients enrolled in regimen A who completed at least 6 months of therapy, 14 (74%) had sputum samples become culture-negative. Of 39 patients enrolled in regimen B who completed at least 6 months of therapy, 24 (62%) had sputum conversion. These sputum conversion rates are comparable to previous rates at 6 months in patients receiving daily clarithromycin- or azithromycin-containing regimens. No resistance to azithromycin emerged with either regimen. This is the first study to demonstrate the efficacy of intermittent administration of medication for MAC lung disease.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifabutin; Streptomycin; Treatment Outcome

The therapeutic efficacy of oral macrolides (erythromycin base and midekamycin, macropen) and azalides (azithromycin, sumamed) in the treatment of children with acute and chronic (during the aggravation) bronchopulmonary diseases was studied. The main etiological factors of acute and chronic pneumonia were Streptococcus pneumoniae and Haemophilus influenzae. The proportion of Staphylococcus aureus was high in infants with acute pleuropulmonary inflammations. The susceptibility of the isolates to the antibiotics was found to be high. The results of the trials showed that erythromycin, macropen and azithromycin were efficient in the treatment of acute and chronic pneumonia. The foci of acute pneumonia dissolved after oral administration of the drugs within the same periods as after the use of other parenteral antibiotics. The comparative estimation of the drug efficacy revealed that azithromycin was more active. The ease of the azithromycin administration (in the form of a suspension) in infants and children once a day for a shorter treatment course up to 5 days, high efficacy and no adverse reactions permitted to consider the antibiotic as the most promising antibacterial agent for the treatment of respiratory infections in children in hospitals and outpatient departments.

Topics: Administration, Oral; Azithromycin; Bronchial Diseases; Erythromycin; Humans; Infant; Infant, Newborn; Leucomycins; Lung Diseases

Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung. The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy. At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h). Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium. All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l-1) after 96 h (168 h after the first dose). Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose). Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined. The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Azithromycin; Humans; Lung; Lung Diseases; Lymph Nodes; Thoracotomy; Tissue Distribution

Mycobacterium avium complex (MAC) thrives in various environments and mainly causes lung disease in humans. Because macrolide antibiotics such as clarithromycin or azithromycin are key drugs for MAC lung disease, the emergence of macrolide-resistant strains prevents the treatment of MAC. More than 95% of macrolide-resistant MAC strains are reported to have a point mutation in 23S rRNA domain V. This study successfully developed a melting curve assay using nonfluorescent labeled probes to detect the MAC mutation at positions 2058 to 2059 of the 23S rRNA gene (AA genotype, clarithromycin susceptible; TA, GA, AG, CA, AC, and AT genotypes, clarithromycin resistant). In the AA-specific probe assay, the melting peak of the DNA fragment of the AA genotype was higher than that of DNA fragments of other genotypes. Melting temperature (

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Lung Diseases; Macrolides; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis

Long-term azithromycin (AZM) treatment reduces the frequency of acute respiratory exacerbation in children and adolescents with HIV-associated chronic lung disease (HCLD). However, the impact of this treatment on the respiratory bacteriome is unknown.. African children with HCLD (defined as forced expiratory volume in 1 s z-score (FEV1z) less than - 1.0 with no reversibility) were enrolled in a placebo-controlled trial of once-weekly AZM given for 48-weeks (BREATHE trial). Sputum samples were collected at baseline, 48 weeks (end of treatment) and 72 weeks (6 months post-intervention in participants who reached this timepoint before trial conclusion). Sputum bacterial load and bacteriome profiles were determined using 16S rRNA gene qPCR and V4 region amplicon sequencing, respectively. The primary outcomes were within-participant and within-arm (AZM vs placebo) changes in the sputum bacteriome measured across baseline, 48 weeks and 72 weeks. Associations between clinical or socio-demographic factors and bacteriome profiles were also assessed using linear regression.. AZM treatment preserved sputum bacterial diversity and reduced the relative abundances of the HCLD-associated genera Haemophilus and Moraxella. These bacteriological effects were associated with improvement in lung function and may account for reduced respiratory exacerbations associated with AZM treatment of children with HCLD. Video Abstract.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Load; Child; Haemophilus; HIV Infections; Humans; Lung; Lung Diseases; Moraxella; RNA, Ribosomal, 16S; Sputum

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

Topics: Aged; Amikacin; Antitubercular Agents; Azithromycin; Biomarkers; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Stem Cells

Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics.. What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens?. We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form.. Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]).. Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Topics: Administration, Inhalation; Aged; Amikacin; Anti-Bacterial Agents; Azithromycin; Clofazimine; Drug Therapy, Combination; Female; Humans; Imipenem; Lung Diseases; Male; Middle Aged; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Prospective Studies

This study aimed to compare the discontinuation rates attributed to adverse events and treatment outcomes between clarithromycin (CLR) and azithromycin (AZM) in patients with Mycobacterium avium complex lung disease (MAC-LD).. Among patients diagnosed with MAC-LD during 2001-2013, 560 for whom treatment was initiated as a guideline-based therapy until May 2018 were selected for adverse event analysis. Of them, 316 who underwent treatment for ≥12 months were selected for outcome analysis. Their medical records were retrospectively reviewed. The discontinuation and treatment success rates were analysed after adjustments using the inverse probability of treatment weighted (IPTW) method.. Among the 560 patients, 466 (83.2%) and 94 (16.8%) started CLR-containing and AZM-containing regimens, respectively. The IPTW method using propensity scoring revealed that the discontinuation rate attributed to adverse events was significantly higher with CLR than AZM use (24.6% vs. 9.6%; P=0.001). The overall treatment success rate of the 316 patients who received guideline-based therapy for ≥12 months was 83.2%. Analysis adjusted by the IPTW method showed no significant difference in the treatment success rate between the use of CLR and AZM. Furthermore, 1-year and 3-year recurrence rates were similar with the two drugs (6.8% vs. 6.0%; P>0.999 and 31.0% vs. 37.5%; P=0.482, respectively).. These findings suggest that an AZM-containing regimen may be the better initial treatment choice for MAC-LD as it resulted in lesser discontinuation rates attributed to adverse events while offering similar patient outcomes when compared with CLR.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Humans; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Propensity Score; Retrospective Studies; Treatment Outcome

To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization.. We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization.. A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization.. Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antiviral Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Autoimmune Diseases; Azithromycin; Betacoronavirus; Comorbidity; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunosuppressive Agents; Logistic Models; Lopinavir; Lung Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Pandemics; Pneumonia, Viral; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Sex Factors; Spain

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Azithromycin; Betacoronavirus; Black or African American; Cannula; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Female; Healthcare-Associated Pneumonia; Heart Diseases; Hispanic or Latino; Humans; Hydroxychloroquine; Hypertension; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Intubation, Intratracheal; Lung Diseases; Male; Middle Aged; Oxygen Inhalation Therapy; Pandemics; Philadelphia; Pneumonia, Ventilator-Associated; Pneumonia, Viral; Pulse Therapy, Drug; Renal Insufficiency, Chronic; Respiratory Insufficiency; Retrospective Studies; SARS-CoV-2; Severity of Illness Index; Smoking; White People

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary

Topics: Antitubercular Agents; Azithromycin; Body Mass Index; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Odds Ratio; Treatment Outcome

Mycobacterium abscessus and Mycobacterium massiliense are grouped as the Mycobacterium abscessus complex. The aim of this study was to elucidate the differences between M. abscessus and M. massiliense lung diseases in terms of progression rate, treatment outcome, and the predictors thereof.. Between 1 January 2006 and 30 June 2015, 56 patients and 54 patients were diagnosed with M. abscessus and M. massiliense lung diseases, respectively. The time to progression requiring treatment and treatment outcomes were compared between the 2 groups of patients, and predictors of progression and sustained culture conversion with treatment were analyzed. In addition, mediation analysis was performed to evaluate the effect of susceptibility to clarithromycin on treatment outcomes.. During follow-up, 21 of 56 patients with M. abscessus lung diseases and 21 of 54 patients with M. massiliense lung diseases progressed, requiring treatment. No difference was detected in the time to progression between the 2 patient groups. Lower body mass index, bilateral lung involvement, and fibrocavitary-type disease were identified as predictors of disease progression. Among the patients who began treatment, infection with M. massiliense rather than M. abscessus and the use of azithromycin rather than clarithromycin were associated with sustained culture conversion. The difference in treatment outcomes was partly mediated by the organism's susceptibility to clarithromycin.. Progression rates were similar but treatment outcomes differed significantly between patients with lung disease caused by M. abscessus and M. massiliense. This difference in treatment outcomes was partly explained by the susceptibility of these organisms to clarithromycin.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Progression; Female; Humans; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Retrospective Studies; Risk Factors; Sputum; Treatment Outcome

Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.. Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 μg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings.. Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found.. Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Clarithromycin; Drug Resistance, Bacterial; Female; Humans; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Risk Factors; Serum Albumin; Sputum; Tomography, X-Ray Computed; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Bronchial Fistula; Cysts; Ethambutol; Humans; Hydropneumothorax; Immunocompromised Host; Liver Diseases; Lung; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pleura; Rifampin; Tomography, X-Ray Computed

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

Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experiences with treatment regimens and durations. In the case presented herein, two different treatment regimens were applied to an immunocompromised HIV-negative patient with primary skin involvement and extensive pulmonary involvement due to suspected relapse on isoniazid, ethambutol, and clarithromycin treatment. The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Lung; Lung Diseases; Mycobacterium; Mycobacterium Infections; Pyrazinamide; Radiography

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

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+)  cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1β, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1β/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bronchitis; Bronchoalveolar Lavage; C-Reactive Protein; Cytokines; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Lung Diseases; Lung Transplantation; Lymphocytes; Male; Middle Aged; Pneumonia; Postoperative Complications; Prognosis; Prospective Studies; Respiratory Function Tests; Retrospective Studies; Spirometry; Transplantation, Homologous; Young Adult

Chronic rejection is the major problem hampering long-term survival after lung transplantation. Recently, it became clear that patients may develop an obstructive (bronchiolitis obliterans syndrome [BOS]) or a restrictive lung function defect (restrictive allograft syndrome [RAS]), for which specific risk factors are unknown.. A retrospective analysis of our lung transplantation cohort was performed (n=380). Patients with an irreversible decline in forced expiratory volume in 1 second were identified and classified as BOS or RAS. Patient characteristics, bronchoalveolar lavage (BAL) cellularity, rates of respiratory tract infection, colonization, acute rejection, and lymphocytic bronchiolitis were compared between BOS, RAS, and stable patients.. There were 103 patients suffering from chronic rejection, of which 79 had BOS and 24 were diagnosed with RAS. There were more patients with infection and pseudomonal colonizations in BOS and RAS compared with control (P=0.0090 and P=0.0034, respectively). More patients ever experienced acute and severe acute rejections (A≥2; both P<0.0001) and lymphocytic bronchiolitis (P=0.0006) in BOS and RAS versus control. There were more patients experiencing severe lymphocytic bronchiolitis in RAS compared with BOS (P=0.031). BAL neutrophilia in BOS and RAS were elevated at days 360, 540, and 720 versus control. BOS, but especially RAS patients, experienced more frequent episodes of increased BAL eosinophilia (≥2%; P<0.0001).. Acute rejection, lymphocytic bronchiolitis, colonization with pseudomonas, infection, and BAL eosinophilia and neutrophilia are risk factors for the later development not only of RAS but also of BOS.

Topics: Adult; Azithromycin; Bronchiolitis Obliterans; C-Reactive Protein; Female; Graft Rejection; Humans; Immunosuppressive Agents; Interleukin-8; Lung Diseases; Lung Transplantation; Male; Middle Aged; Retrospective Studies; Risk Factors; Transplantation, Homologous

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

Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

Topics: Administration, Inhalation; Adolescent; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Cystic Fibrosis; Female; France; Humans; Lung Diseases; Male; Mycobacterium Infections; Nontuberculous Mycobacteria; Prevalence; Registries; Risk Factors; Young Adult

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Humans; Inflammation; Lung Diseases; Lung Transplantation; Placebos; Retrospective Studies

Topics: Adolescent; Anti-Infective Agents; Azithromycin; Bronchoscopy; Ceftriaxone; Factor VIII; Hemophilia A; Hemorrhage; Humans; Lung Diseases; Male; Pulmonary Alveoli; Radiography; Sulfamethoxazole; Treatment Outcome; Trimethoprim

Ureaplasma infection is associated with increased lung disease in high-risk neonates. Our goal was to determine the impact of antibiotic prophylaxis on Ureaplasma and oxygen-induced lung disease in newborn mice. In animal model development and prophylaxis experiments, pups were randomly assigned to either 0.8 or 0.21 inspired oxygen concentration [fraction of inspired oxygen (FiO2)] from 1 to 14 d of age and either Ureaplasma or 10 B media daily from 1 to 3 d. All pups were observed for growth and survival. Surviving pups had culture and PCR evaluated for blood, bronchoalveolar lavage, and lung, and lung weights, pathology, morphometry, histology, and immunohistochemistry were determined. In prophylaxis experiments, erythromycin, azithromycin, or normal saline was given for the first 3 d, and minimum inhibitory concentration and pharmacokinetics were determined. In model development, 0.8 FiO2 and Ureaplasma infection survival and growth were significantly decreased and lung edema and inflammation were significantly increased. In prophylaxis experiments, we observed significantly improved survival and growth with azithromycin versus normal saline controls, whereas erythromycin was not significantly different from controls, and decreased inflammatory response with azithromycin versus normal saline and erythromycin. In a neonatal mouse model of Ureaplasma and oxygen-induced lung disease, appropriate antibiotic prophylaxis improves survival and morbidity and decreases lung inflammation.

Topics: Animals; Animals, Newborn; Animals, Suckling; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Bronchoalveolar Lavage Fluid; Female; Humans; Infant, Newborn; Lung Diseases; Mice; Pregnancy; Random Allocation; Survival Rate; Ureaplasma; Ureaplasma Infections

Azithromycin (AZM) is widely used for the treatment of respiratory infection. Macrolides are generally well tolerated and adverse reactions are extremely rare. A 78-year-old man was treated with AZM for upper respiratory infection in November 2007. He developed bloody sputum at 5 days after AZM administration. Chest X-ray and CT images revealed diffuse ground glass opacities in the bilateral lung fields. Bronchoalveolar lavage demonstrated bloody fluid. The clinical symptoms and CT image improved after the corticosteroid therapy. His past history revealed that he also developed similar clinical symptoms and radiological features after treatment with AZM for upper respiratory infection at another hospital in October 2006. At that time, his condition improved after the administration of corticosteroid under a diagnosis of interstitial lung disease of unknown etiology. Finally, we diagnosed recurrent alveolar hemorrhage caused by re-administration of AZM. This is apparently the first reported case of AZM-induced diffuse alveolar hemorrhage.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Hemorrhage; Humans; Lung Diseases; Male

The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) has been shown to improve the lung function of CF patients. The present study was conducted in accordance with previous in vitro studies suggesting that the effect of AZM may be the inhibition of alginate production, blockage of quorum sensing (QS), and increased sensitivity to hydrogen peroxide and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results in the suppression of QS-regulated virulence factors, significantly improves the clearance of P. aeruginosa alginate biofilms, and reduces the severity of the lung pathology compared to that in control mice. We conclude that AZM attenuates the virulence of P. aeruginosa, impairs its ability to form fully polymerized alginate biofilms, and increases its sensitivity to complement and stationary-phase killing, which may explain the clinical efficacy of AZM.

Topics: Alginates; Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Azithromycin; Cystic Fibrosis Transmembrane Conductance Regulator; Dose-Response Relationship, Drug; Female; Humans; Hydrogen Peroxide; Lung; Lung Diseases; Male; Mice; Mice, Knockout; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Virulence Factors

Topics: Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Bronchoscopy; Ceftriaxone; Drug Therapy, Combination; Floxacillin; Hemorrhage; Humans; Leptospira; Leptospirosis; Lung Diseases; Male; Pneumonia, Bacterial; Radiography, Thoracic

Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniae and treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P > 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniae counts versus those for the controls; this finding did not differ significantly (P > 0.05) from the results observed for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important role in C. pneumoniae infection. Blockage of integrin activation led to a significant inhibition of C. pneumoniae infection in HeLa cells. Moreover, CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer new perspectives on the treatment of C. pneumoniae infection and indicate that alpha(v)beta(3) could be a promising target for new agents developed for activity against this pathogen.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; CHO Cells; Cricetinae; Disease Models, Animal; HeLa Cells; Humans; Integrin alphaV; Integrin beta3; Lung Diseases; Male; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Treatment Outcome

M. malmoense could be cultivated in sputum samples of a 49-year-old patient with destructive pulmonary disease. The conventional antituberculous therapy (started because initially a presumptive diagnosis of tuberculosis was established) was altered to ethambutol, rifabutin, clarithromycin and ciprofloxacin, followed by a long-time therapy with azithromycin or clarithromycin. But till now it was not possible to eradicate the mycobacteria from the respiratory tract (insufficient compliance, interruptions of the therapy due to side effects, excessive smoking). Infections due to M. malmoense are rare events. Many patients have disposing underlying diseases. In most cases it is a pulmonary infection. The most frequent used antibiotics are rifampicin (or rifabutin), ethambutol and clarithromycin.

Topics: Azithromycin; Clarithromycin; Drug Therapy, Combination; Ethambutol; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Rifampin

We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, /=64 micro g/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of S. pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Clarithromycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Half-Life; Humans; Lung Diseases; Mice; Microbial Sensitivity Tests; Serotyping; Streptococcal Infections; Streptococcus pneumoniae

The number of adults with cystic fibrosis (CF) is increasing. They are striving for independence and a fulfilling life with focus on career, relationships, education and finances at a time when lung function is likely to be declining and complications of this multi-system disease are increasing. Maintaining the quality and improving the duration of life are continuing challenges for the -clinician and the patient. Increased hope and greater expectations have been provided by a number of recent clinical advances and active research into novel treatments, including gene therapy. There has been increased recognition of the necessity for early diagnosis, adequate monitoring and effective intervention for complications such as diabetes and osteoporosis. Research into multi-resistant bacteria and clonal strains of Pseudomonas aeruginosa is ongoing and attention has focused on infection control policies. Although more high-level evidence is required on many issues confronting people with CF, a considerable effort has been made over the last decade to provide a more evidence-based approach to therapy with a number of large controlled clinical trials. For the adult with CF, there are also more decisions to be made. There is focus on reproductive health, with most couples enjoying the real possibility of having children. For those with advanced disease, the option for lung transplantation is well established. Maintenance of quality care will require adequate planning, effective transition programmes from paediatric to adult care, specialized training for doctors, nurses and allied health professionals and the allocation of sufficient resources to accommodate the inevitable increase in patient numbers.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Clinical Trials as Topic; Cystic Fibrosis; Humans; Lung Diseases; Osteoporosis; Pseudomonas Infections

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

Ninety-two patients were assessable in 3 consecutive, open, noncomparative, prospective, controlled, single-center trials of the use of multidrug regimens that contain azithromycin for treating pulmonary Mycobacterium avium complex (MAC) disease. Azithromycin was provided at a dose of 300-600 mg per day with oral companion drugs administered daily (regimen A, 29 patients); 600 mg 3 times weekly (t.i.w.), with oral companion drugs administered daily (regimen B, 20 patients); and 600 mg (t.i.w.), with oral companion drugs administered t.i.w. (regimen C, 43 patients). All regimens included rifabutin (or rifampin) and ethambutol as companion drugs as well as initial streptomycin. Treatment success was defined as 12 months of negative cultures while on therapy. Treatment failure was defined as sputum culture positivity after at least 6 months of therapy. Of the patients in each regimen who reached study end points, 17 of 29 (59%) were in regimen A, 11 of 20 (55%) were in regimen B, and 28 of 43 (65%) were in regimen C met the treatment success criterion. There were no statistically significant differences in outcome between the 3 regimens. These studies demonstrate the effectiveness of daily and t.i.w. regimens containing azithromycin for treatment of MAC lung disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Drug Therapy, Combination; Drug Tolerance; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifabutin; Rifampin; Streptomycin; Treatment Outcome

Topics: Animals; Anti-Bacterial Agents; Drug Design; Drug Resistance, Microbial; Haemophilus influenzae; Lung; Lung Diseases; Macrolides; Mice; Models, Molecular; Rats; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Structure-Activity Relationship

Twenty-one neonatal respiratory isolates of Ureaplasma urealyticum were serotyped, and their susceptibilities to ciprofloxacin, gentamicin, chloramphenicol, erythromycin, azithromycin, and doxycycline were tested. Most patient strains were Ureaplasma urealyticum bv. parvum. Chloramphenicol, doxycycline, and azithromycin had the lowest MICs. This data may be useful when designing prophylactic or therapeutic trials of antibiotics for chronic lung disease of the newborn.

Topics: Anti-Bacterial Agents; Azithromycin; Chloramphenicol; Doxycycline; Humans; Infant, Newborn; Lung Diseases; Microbial Sensitivity Tests; Respiratory System; Ureaplasma Infections; Ureaplasma urealyticum

The dynamics of clarithromycin and azithromycin efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation. Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy. Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 microgram/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7. The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Lung Diseases; Rats; Rats, Sprague-Dawley

We initiated a prospective trial of an azithromycin-containing regimen for the treatment of human immunodeficiency virus-negative patients with Mycobacterium avium complex (MAC) lung disease; the initial 4 months of therapy were with azithromycin (600 mg/d) alone. The primary study endpoint was microbiological response measured at 4 and 6 months of therapy. Of 29 patients enrolled in the study, 23 completed therapy. Fifty-two percent of these 23 patients were male, and 65% were smokers. All 23 patients were older than 45 years of age; 83% had bilateral disease, and 48% had fibrocavitary disease. Macrolide (clarithromycin)-susceptible MAC isolates were recovered from these 23 patients before treatment. Cultures of sputum from 38% of these patients became negative, and the positivity of cultures of sputum from 76% of these patients was significantly reduced. Sixty-eight percent of sputum cultures were strongly positive (> 200 colonies) before therapy, while only 27% were strongly positive after therapy. Although most patients continued to receive 600 mg of azithromycin/d, the high incidence of gastrointestinal side effects (76%) and altered hearing (41%) suggests the need for lower or less frequent dosing. Macrolide (clarithromycin) resistance did not develop in any MAC isolates during monotherapy. These results, which demonstrate that azithromycin is active against MAC pulmonary disease, provide a rationale to include this drug in the initial multidrug regimens recommended for the treatment of this disease.

Topics: Aged; Aged, 80 and over; Azithromycin; Consumer Product Safety; Drug Tolerance; Female; Follow-Up Studies; HIV Infections; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies

Topics: Azithromycin; Clarithromycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; HIV; Humans; Leukocyte Count; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Platelet Count; Rifabutin

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Lung Diseases; Male; Urethritis; Uterine Cervicitis

Topics: Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Female; Humans; Lung Diseases; Male; Tonsillitis; Urethritis; Uterine Cervicitis

Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Topics: Azithromycin; Bacterial Infections; Bronchi; Bronchoalveolar Lavage Fluid; Cell Count; Epithelium; Erythromycin; Female; Humans; Lung Diseases; Macrophages; Male; Sputum