zithromax and Chronic-Disease

Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021.. To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.. Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.. Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.. We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials, 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials, 1660 participants; very low-certainty evidence). Based on an analysis of evaluable participants, we are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials, 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials, 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79 (95% CI 0.57 to 1.09; 6 trials, 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials, 802 participants; low-certainty evidence). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. Azithromycin versus amoxicillin Based on one unpubli. We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Child; Chronic Disease; Humans; Infant; Macrolides; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Recurrence; Streptococcus pyogenes; Systematic Reviews as Topic

The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.

Topics: Acute Coronary Syndrome; Anti-Bacterial Agents; Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Betacoronavirus; Cardiotonic Agents; Chronic Disease; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Enzyme Inhibitors; Extracorporeal Membrane Oxygenation; Heart Failure; Heart-Assist Devices; Humans; Hydroxychloroquine; Intra-Aortic Balloon Pumping; Myocardial Infarction; Myocarditis; Pandemics; Percutaneous Coronary Intervention; Pneumonia, Viral; SARS-CoV-2; Shock, Cardiogenic; Thromboembolism

Azithromycin is a macrolide widely used in chronic bronchial diseases due to its anti-inflammatory properties. This treatment is prescribed to patients with bronchiectasis, asthma and severe chronic obstructive pulmonary disease who present more than 3 exacerbations per year or a deterioration of respiratory function despite an optimal treatment. Macrolides decrease the number of exacerbation but azythromycine must be prescribed carefully. Indeed, it involves potential cardiovascular and otological toxicities and the emergence of resistant bacteria. In addition, studies remain insufficient to establish the optimal dosage and duration of azithromycine.

Topics: Azithromycin; Bronchial Diseases; Chronic Disease; Humans; Patient Selection

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; Haemophilus Infections; History, 20th Century; History, 21st Century; Humans; Japan; Macrolides; Nasal Polyps; Rhinitis; Sinusitis

Chronic lung allograft dysfunction (CLAD) was recently introduced as an overarching term mainly to classify patients with chronic rejection after lung transplantation, although other conditions may also qualify for CLAD. Initially, only the development of a persistent and obstructive pulmonary function defect, clinically identified as bronchiolitis obliterans syndrome (BOS), was considered as chronic rejection, if no other cause could be identified. It became clear in recent years that some patients do not qualify for this definition, although they developed a chronic and persistent decrease in FEV1 , without another identifiable cause. As the pulmonary function decline in these patients was rather restrictive, this was called restrictive allograft syndrome (RAS). In the present review, we will further elaborate on these two CLAD phenotypes, with specific attention to the diagnostic criteria, the role of pathology and imaging, the risk factors, outcome, and the possible treatment options.

Topics: Allografts; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Disease Progression; Forced Expiratory Volume; Fundoplication; Gastroesophageal Reflux; Graft Rejection; Humans; Lung Transplantation; Neutrophils; Phenotype; Postoperative Complications

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 lung allograft dysfunction is a major challenge in long-term management of lung transplant recipients. Both alloimmune-dependent factors (rejection) and alloimmune-independent factors contribute to the development of chronic lung allograft dysfunction. Thus, use of the term "chronic rejection" tends to be intentionally avoided among specialists in the field, although "chronic rejection" is still an acceptable lay word understood by many patients. Several different phenotypes have been identified in chronic lung allograft dysfunction, including restrictive allograft syndrome, neutrophilic reversible allograft dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft syndrome is characterized by restrictive physiology and peripheral foci of inflammation and fibrosis, which contrasts the obstructive physiology and pathological foci in small airways in conventional bronchiolitis obliterans syndrome. Among patients with bronchiolitis obliterans syndrome, there is a subpopulation that responds relatively well to azithromycin. Because these patients show airway neutrophilia, this subtype of chronic lung allograft dysfunction was named neutrophilic reversible allograft dysfunction. Conversely, patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show airway fibrosis with less inflammation (fibrous bronchiolitis obliterans syndrome). In general, restrictive allograft syndrome shows poorer survival than does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans syndrome (within 2 years) shows a worse prognosis than does late-onset bronchiolitis obliterans syndrome. Until preventive and therapeutic options are refined, chronic lung allograft dysfunction will remain a major life-limiting factor. It has significant psychological, physical, social, and economic impacts. Early introduction of palliative care is another important strategy to improve patients' quality of life.

Topics: Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Humans; Lung; Lung Transplantation; Primary Graft Dysfunction; Syndrome; Terminology as Topic; Transplantation, Homologous

Chronic lung allograft rejection is the single most important cause of death in lung transplant recipients after the first postoperative year, resulting in a 5-year survival rate of approximately 50%, which is far behind that of other solid organ transplantations. Spirometry is routinely used as a clinical marker for assessing pulmonary allograft function and diagnosing chronic lung allograft rejection after lung transplantation (LTx). As such, a progressive obstructive decline in pulmonary allograft function (forced expiratory volume in 1 sec [FEV1]) in absence of all other causes (currently defined as bronchiolitis obliterans syndrome [BOS]) is considered to reflect the evolution of chronic lung allograft rejection. BOS has a 5-year prevalence of approximately 45% and is thought to be the final common endpoint of various alloimmunologic and nonalloimmunologic injuries to the pulmonary allograft, triggering different innate and adaptive immune responses. Most preventive and therapeutic strategies for this complex process have thus far been largely unsuccessful. However, the introduction of the neomacrolide antibiotic azithromycin (AZI) in the field of LTx as of 2003 made it clear that some patients with established BOS might in fact benefit from such therapy due to its various antiinflammatory and immunomodulatory properties, as summarized in this review. Particularly in patients with an increased bronchoalveolar lavage neutrophilia (i.e., 15%-20% or more), AZI treatment could result in an increase in FEV1 of at least 10%. More recently, it has become clear that prophylactic therapy with AZI actually may prevent BOS and improve FEV1 after LTx, most likely through its interactions with the innate immune system. However, one should always be aware of possible adverse effects related to AZI when implementing this drug as prophylactic or long-term treatment. Even so, AZI therapy after LTx can generally be considered as safe.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Graft Rejection; Humans; Immunologic Factors; Lung Transplantation; Transplantation, Homologous

Helicobacter bilis, an unusual cause of chronic infections in patients with X-linked agammaglobulinemia (XLA), is notoriously difficult to diagnose and eradicate. Based on the limited number of cases reported worldwide, we highlight the typical features of H. bilis infection in XLA and provide a rational and successful approach to diagnosis and treatment of this challenging infection.

Topics: Adolescent; Adult; Agammaglobulinemia; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Chronic Disease; Ertapenem; Genetic Diseases, X-Linked; Helicobacter; Helicobacter Infections; Humans; Male; Ofloxacin; Phylogeny; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Cerebral Palsy; Child; Chronic Disease; Humans; Male; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or clarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and clarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Aza Compounds; Azithromycin; Bronchitis, Chronic; Chronic Disease; Clarithromycin; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Fluoroquinolones; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Moxifloxacin; Multicenter Studies as Topic; Quinolines; Randomized Controlled Trials as Topic; Treatment Outcome

It has been recognized for more than 20 years that the macrolides have immunomodulatory effects that are beneficial for those suffering from chronic pulmonary inflammatory syndromes, such as diffuse panbronchiolitis, cystic fibrosis, asthma and bronchiectasis. The macrolides have consistently been associated with decreased length of stay and mortality when used alone or in combination with beta-lactam antibiotics. This effect can be demonstrated against combinations consisting of beta-lactams and other antibiotics active against 'atypical chest pathogens' when treating community-acquired pneumonia (CAP) in hospitalized patients. As such, it appears that the macrolides' effects in CAP patients are more than just antibacterial in nature. AIMS OF THIS REVIEW: This review aims: to give the reader information on the background areas described, as well as related areas; to review the CAP benefits with macrolides and how they may be related to the immunomodulatory properties they demonstrate, albeit in a shorter period of time than previously demonstrated with chronic pulmonary disorders; to use ex vivo data to support these extrapolations.. A literature search using Medline was conducted from 1966 onwards, searching for articles with relevant key words such as macrolide, diffuse panbronchiolitis, community-acquired pneumonia, biofilm, immunomodulation, cystic fibrosis, erythromycin, clarithromycin, roxithromycin and azithromycin, bronchiectasis and asthma. When appropriate, additional references were found from the bibliographies of identified papers of interest. Any relevant scientific conference proceedings or medical texts were checked when necessary.. (1) Research into macrolide immunomodulation for chronic pulmonary disorders demonstrates consistent positive effects, although of types other than seen with diffuse panbronchiolitis. These effects, together with their inhibitory activity on biofilms, have the potential to make them a useful option. (2) The benefits for CAP are consistent, and higher when a macrolide is given with another atypical agent than if the other atypical agent is given alone, suggesting a non-antibacterial benefit. (3) Recent research of the immunomodulatory properties of azithromycin imply that azithromycin may have a previously unknown short-term biphasic effect on inflammation modulation: enhancement of host defence mechanisms shortly after initial administration followed by curtailment of local infection/inflammation in the following period. (4) Additional in vivo research is needed prior to developing any firm conclusions.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Chronic Disease; Clarithromycin; Community-Acquired Infections; Erythromycin; Humans; Inflammation; Macrolides; Respiratory Tract Infections

Chronic rejection (obliterative bronchiolitis) is the single most important cause of chronic allograft dysfunction and late mortality after lung transplantation. As this condition is difficult to prove using biopsy specimens, a clinical term, bronchiolitis obliterans syndrome (BOS) has been in use for >10 yrs to describe the progressive decrease of pulmonary function. However, before diagnosing a patient as having BOS, based on a sustained and progressive decrease in forced expiratory volume in one second and/or forced mid-expiratory flow between 25-75% of forced vital capacity, different confounding factors have to be eliminated. Treatment of BOS mainly consists of an increase or a change in the immunosuppressive drug regimen, which may lead to more pronounced infectious complications. Recently, two new options have become available to treat patients with BOS, treatment of gastro-oesophageal reflux and azithromycin. In the present paper, the authors give an overview of the current data on these two modalities, which may lead to a restoration of the pulmonary function in some of the patients, illustrating once more the fact that bronchitis obliterans syndrome is not always a manifestation of chronic rejection.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Gastroesophageal Reflux; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Respiratory Function Tests; Risk Factors; Syndrome

Topics: Anti-Infective Agents; Asthma; Azithromycin; Bronchiolitis; Chronic Disease; Clinical Trials as Topic; Cystic Fibrosis; Erythromycin; Gene Expression Regulation, Bacterial; Humans; Macrolides; Mucins; Neutrophils; Pancreatic Elastase; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Sinusitis; Structure-Activity Relationship

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis; Chronic Disease; Clarithromycin; Erythromycin; History, 20th Century; Humans; Japan; Lung Neoplasms; Respiratory Tract Infections

We carried out a meta-analysis of randomized controlled trials of azithromycin compared with other antibiotics in the treatment of lower respiratory tract infections, including acute bronchitis (five comparisons including 1372 patients), acute exacerbations of chronic bronchitis (13 comparisons including 1342 patients) and community-acquired pneumonia (18 comparisons with 1664 patients). For the first two indications, azithromycin did not offer any statistically significant reduction in clinical failures [random effects odds ratios 0.84, 95% confidence interval (CI) 0.54-1.31 and 0.64, 95% CI 0.31-1.32, respectively] and absolute risk differences were small. For community-acquired pneumonia, azithromycin significantly reduced clinical failures by about one-third (random effects odds ratio 0.63, 95% CI 0.41-0.95). The absolute incremental benefit was approximately one clinical failure prevented per 50 treated patients with community-acquired pneumonia. There was no significant heterogeneity for different comparators and for bacterial versus atypical pneumonias. Azithromycin was discontinued because of adverse events in only 23 of 3487 patients (0.7%). Although results should be interpreted cautiously as most trials were open-label and susceptible to bias, the meta-analysis indicates that, compared with antibiotics with traditional pharmacokinetics that require more prolonged courses, azithromycin offers no significant advantage for bronchitis, but may be more effective in community-acquired pneumonia.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchitis; Chi-Square Distribution; Chronic Disease; Community-Acquired Infections; Confidence Intervals; Humans; Odds Ratio; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections

Azithromycin is a molecule of the macrolide family, belonging to the azalides class. Several of its characteristics allow for its use in the treatment of the community-acquired lower respiratory tract infections. Commonly isolated pathogens in bronchial infections are most frequently H. influenzae, S. pneumoniae, M. catarrhalis, C. pneumoniae and M. pneumoniae, and more rarely or in the context of a particular background, S. aureus, Gram negative bacteria and L. pneumophila. MIC90 of these germs is generally low or slightly elevated, displaying an inhibitory activity of the azithromycin on these bacteria. Nevertheless, the frequency of macrolide-resistant S. pneumoniae is not negligible and this germ must be considered as inconstantly susceptible to the macrolide family. Pharmacokinetics studies evidenced from high to very high azithromycin concentrations in the pulmonary tissues, reaching values well above MIC of pathogens commonly isolated. Given the long half-life, these concentrations persist a long time after oral administration. As azithromycin concentrates much in polymorphonuclear leucocytes, they release azithromycin after having migrated into the infectious site by chimiotactism, thus allowing to increase the antibiotic concentration at infection site. These requirements have been confirmed in vivo in animal models and in clinical studies. Two experimental models on macrolide susceptible S. pneumoniae, and H. influenzae evidenced a better activity of azithromycin in comparison to other macrolides tested against these two germs.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Azithromycin; Bronchitis; Chronic Disease; Community-Acquired Infections; Haemophilus Infections; Humans; Mice; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal

To evaluate the yearly prevalence and annual transition of multi-drug-resistant-chronic endometritis (MDR-CE) in infertile women with a history of repeated implantation failure (RIF) and to establish the third-line antibiotic treatment regimen against MDR-CE.. This retrospective/prospective cohort and pilot study included 3473 RIF women between April 2010 and September 2021. The endometrial stromal plasmacyte density index (ESPDI) was calculated in 3449 CD138-immunostained endometrial sections to evaluate CE. The microbiota in the vaginal secretions and endometrial fluid was compared between 17 patients with MDR-CE and 16 patients with antibiotics-sensitive CE. In a pilot study, oral moxifloxacin (400 mg/day, 10 days, n = 24) or azithromycin (500 mg/day, 3 days, n = 24) was administered to eligible patients with MDR-CE.. From April 2010 to March 2020, CE was detected in 31.4% of RIF women and MDR was detected in 7.8% of CE. While the prevalence of CE was stable for a decade, MDR in CE increased steadily (OR 8.27, 95% CI 2.58-26.43, p trend < 0.001). The bacterial species/communities unique to MDR-CE were not found. The histopathologic cure rate of MDR-CE was similar between the moxifloxacin and azithromycin groups (79.2% vs 75.0%, OR 1.27, 95% CI 0.32-4.89, p value 0.73), as well as reproductive outcomes in subsequent embryo transfer cycles.. In RIF women, MDR in CE increased over the decade. As a third-line treatment for MDR-CE, azithromycin may have a clinical advantage due to its shorter time administration periods.. ClinicalTrials.gov Identifier: UMIN-CTR 000029449/000031909.

Topics: Anti-Bacterial Agents; Azithromycin; Chronic Disease; Embryo Implantation; Endometritis; Endometrium; Female; Humans; Infertility, Female; Moxifloxacin; Pharmaceutical Preparations; Pilot Projects; Prospective Studies; Retrospective Studies

Macrolides have shown beneficial effects in the treatment of chronic rhinosinusitis (CRS). This study aimed to compare the effect of azithromycin and clarithromycin in combination with conventional therapies for the treatment of CRS.. This single-blind randomized controlled trial was conducted during 2018-2019 at the Otorhinolaryngology Clinic of Shahid Mohammadi Hospital, Bandar Abbas, Iran. Out of 102 selected patients, 90 were included in the analysis. Patients were selected through convenience sampling and randomly assigned to two equal groups. In addition to conventional therapies (nasal irrigation, betamethasone injection, oxymetazoline and fluticasone spray, guaifenesin syrup, and steam inhalation), the patients in the clarithromycin group received clarithromycin 500 mg tablets twice daily for four weeks. The other group received azithromycin 500 mg tablets daily for four weeks. Patients' symptoms were evaluated pre- and post-intervention, and the Lund-Mackay (LM) scoring system was used for the staging of CRS based on computed tomography scan findings. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant.. Patients in both groups were comparable in terms of age and sex. Complete resolution of symptoms was significantly higher in the azithromycin group than the clarithromycin group (71.1% vs. 24.4%, P<0.001). Baseline LM scores did not differ significantly between the groups (P=0.120). However, post-intervention, LM scores reduced considerably in both groups, but the change was significantly higher in the azithromycin group (P<0.001).. In combination with conventional therapies for CRS in adults, a four-week course of treatment with azithromycin is more effective than clarithromycin.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Clarithromycin; Humans; Macrolides; Rhinitis; Single-Blind Method; Sinusitis; Treatment Outcome

The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug.. A total of 48 adults with refractory CRS were enrolled in a double-blind, randomized, placebo-controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High-resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis.. From initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate [FDR] < 0.05) obtained from the differential abundance analysis. This was not observed in placebo-treated patients. By the end of treatments, azithromycin-treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo.. A 4-month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

Topics: Adult; Azithromycin; Chronic Disease; Humans; Microbiota; Rhinitis; Sinusitis; Staphylococcus aureus

Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS).. A double-blind, randomized, placebo-controlled trial was completed in a single tertiary-care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high-volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected.. A total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4-month post-ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22-item Sino-Nasal Outcome Test score improvements than patients on placebo (18 vs -0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin-exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8).. Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Double-Blind Method; Endoscopy; Humans; Rhinitis; Sinusitis; Treatment Outcome

A Phase I, single-center investigation found that 8 weeks of antimycobacterial therapy improved sarcoidosis FVC. Safety and efficacy assessments have not been performed in a multicenter cohort.. The objective of this study was to determine the safety and efficacy of antimycobacterial therapy on the physiological and immunologic end points of sarcoidosis.. In a double-blind, placebo-controlled, multicenter investigation, patients with pulmonary sarcoidosis were randomly assigned to receive 16 weeks of concomitant levofloxacin, ethambutol, azithromycin, and rifabutin (CLEAR) or matching placebo to investigate the effect on FVC. The primary outcome was a comparison of change in percentage of predicted FVC among patients randomized to receive CLEAR or placebo in addition to their baseline immunosuppressive regimen. Secondary outcomes included 6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) score, adverse events, and decrease in mycobacterial early secreted antigenic target of 6 kDa (ESAT-6) immune responses.. The intention-to-treat analysis revealed no significant differences in change in FVC among the 49 patients randomized to receive CLEAR (1.1% decrease) compared with the 48 randomized to receive placebo (0.02% increase) (P = .64). Physiological parameters such as the change in 6MWD were likewise similar (P = .91); change in SGRQ favored placebo (-8.0 for placebo vs -1.5 for CLEAR; P = .028). The per-protocol analysis revealed no significant change in FVC at 16 weeks between CLEAR and placebo. There was no significant change in 6MWD (36.4 m vs 6.3 m; P = .24) or SGRQ (-2.3 vs -7.0; P = .14). A decline in ESAT-6 immune responses at 16 weeks was noted among CLEAR-treated patients (P = .0003) but not patients receiving placebo (P = .24).. Despite a significant decline in ESAT-6 immune responses, a 16-week CLEAR regimen provided no physiological benefit in FVC or 6MWD among patients with sarcoidosis.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Ethambutol; Female; Humans; Levofloxacin; Male; Middle Aged; Respiratory Function Tests; Rifabutin; Sarcoidosis, Pulmonary

Alterations in the lung microbiota may drive disease development and progression in patients with chronic respiratory diseases. Following lung transplantation (LTx), azithromycin is used to both treat and prevent chronic lung allograft dysfunction (CLAD). The objective of this study was to determine the association between azithromycin use, CLAD, acute rejection, airway inflammation, and bacterial microbiota composition and structure after LTx.. Bronchoalveolar lavage samples (n = 219) from 69 LTx recipients (azithromycin, n = 32; placebo, n = 37) from a previously conducted randomized placebo-controlled trial with azithromycin were analyzed. Samples were collected at discharge, 1, and 2 years following randomization and at CLAD diagnosis. Bacterial microbial community composition and structure was determined using 16S ribosomal RNA gene sequencing and associated with clinically important variables.. At discharge and following 1 and 2 years of azithromycin therapy, no clear differences in microbial community composition or overall diversity were observed. Moreover, no changes in microbiota composition were observed in CLAD phenotypes. However, acute rejection was associated with a reduction in community diversity (p = 0.0009). Significant correlations were observed between microbiota composition, overall diversity, and levels of inflammatory cytokines in bronchoalveolar lavage, particularly CXCL8.. Chronic azithromycin usage did not disturb the bacterial microbiota. However, acute rejection episodes were associated with bacterial dysbiosis.

Topics: Allografts; Anti-Bacterial Agents; Azithromycin; Bronchoalveolar Lavage Fluid; Chronic Disease; Female; Graft Rejection; Humans; Lung; Lung Transplantation; Male; Microbiota; Middle Aged; Prognosis

Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up.. We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up.. Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up.. Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

Topics: Azithromycin; Chronic Disease; Humans; Nasal Polyps; Quality of Life; Rhinitis; Treatment Outcome

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

Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New approaches are needed for the treatment of this group of patients.. We conducted a randomized, double-blind, placebo-controlled trial to determine whether 250 g of azithromycin three times a week for 8 weeks would affect the Leicester Cough Questionnaire (LCQ) score in 44 patients with treatment-resistant cough. Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes.. There was a clinically important improvement in LCQ score with azithromycin (mean change, 2.4; 95% CI, 0.5 to 4.2) but not placebo (mean change, 0.7; 95% CI, -0.6 to 1.9), but the between-group difference was not statistically significant (P = .12). There were no significant between-group differences for any of the secondary outcome measures. Looking at subgroups of responders, there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin (mean, 6.19; 95% CI, 4.06 to 8.32).. Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo. The use of macrolides for treatment-resistant cough cannot be recommended from this study, but they may have a place in the treatment of chronic cough associated with asthma; this is worthy of further investigation.. WHO International Clinical Trials Registry; No.: ISRCTN75749391. URL: http://apps.who.int.

Topics: Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Chronic Disease; Cough; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

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

Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis.. To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions.. A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention.. A tertiary referral dermatology center in Nashville, Tennessee.. Participants were randomized to receive either the oral concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen or a comparative placebo regimen for 8 weeks with a 180-day follow-up.. Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy.. In the intention-to-treat analysis, the CLEAR-treated group had a mean (SD) decrease in lesion diameter of -8.4 (14.0) mm compared with an increase of 0.07 (3.2) mm in the placebo-treated group (P = .05). The CLEAR group had a significant reduction in granuloma burden and experienced a mean (SD) decline of -2.9 (2.5) mm in lesion severity compared with a decline of -0.6 (2.1) mm in the placebo group (P = .02).. Antimycobacterial therapy may result in significant reductions in chronic cutaneous sarcoidosis lesion diameter compared with placebo. These observed reductions, associated with a clinically significant improvement in symptoms, were present at the 180-day follow-up period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of pathways associated with disease severity and enhanced T-cell function following T-cell receptor stimulation.. clinicaltrials.gov Identifier: NCT01074554.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Azithromycin; CD4-Positive T-Lymphocytes; Chronic Disease; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Rifampin; Sarcoidosis; Severity of Illness Index; Single-Blind Method; Skin Diseases; Transcriptome; Treatment Outcome; Young Adult

Single-dose azithromycin (AZT) has been proved efficient in treating various human Chlamydia infections. However, it has not been thoroughly tested in patients with adult inclusion conjunctivitis (AIC). It is the aim of this study to perform a comparative evaluation of efficacy and safety of one-day AZT with long-term AZT and doxycycline (DOX) regimens in AIC and to present a clinical profile of regression course of the disease.. Eighty-three consecutive adults, with symptoms and signs of chronic conjunctivitis and positive Polymerase Chain Reaction (PCR) for chlamydia, were randomly assigned in four treatment groups; AZT 1-day 1000 mg orally, AZT 500 mg daily 9 and 14 days and DOX 200 mg 21 days orally. Follow-up visits were scheduled 1 and 2 weeks, 1, 3 and 6 months after treatment completion. PCR was repeated at the 2nd post-treatment week to confirm elimination of infectious agent. Detailed record of subjective symptoms and objective signs was performed at all visits. Retreatment rate among groups was evaluated as primary outcome. Regression rate of symptoms/signs among groups was recorded as secondary outcomes.. All treatment groups provided statistically equivalent results of retreatment rate. Statistically significant regression of symptoms/signs was documented, initially from the 1st post-treatment week in general, but 1 month was required for complete patients' relief. Follicles were the most common clinical sign with the earliest regression after successful treatment.. Single-dose azithromycin should be considered as equally reliable treatment option, comparing to long-term alternative regimens for AIC. Patients should wait for one week, until first signs of significant regression become obvious and should consider approximately one month to total relief. Follicles could be reasonably used as a key sign for clinical assessment of treatment success.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chlamydia trachomatis; Chronic Disease; Conjunctivitis, Inclusion; Dose-Response Relationship, Drug; Doxycycline; Drug Therapy, Combination; Humans; Prospective Studies; Retreatment; Treatment Outcome

Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.. In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored.. Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found.. Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.. ClinicalTrials.gov NCT01071161.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Comorbidity; Cough; Double-Blind Method; Female; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Spirometry; Surveys and Questionnaires; 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

Periodontitis is an inflammatory condition affecting teeth resulting in progressive destruction of periodontal ligaments, resorption of alveolar bone and loss of teeth. Treatment of periodontitis includes surgical and non surgical management. Systemic antibiotics are also used for the treatment of periodontitis. The aim of this research was to formulate smart gel system of azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in the treatment of periodontitis, was formulated into smart gels using biodegradable, thermosensitive polymer Pluronic® F-127 (PF-127) and Hydroxy Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for sterility, content uniformity, gelation temperature and time, syringeability, rheological behavior, in vitro diffusion and in vivo efficacy in human patients. The prepared smart gels were clear and transparent, sterile, thermoresponsive and injectable. Viscosity of gels increased with increase in concentration of polymer/co-polymer and also with temperature. They gelled in short response time below the body temperature. In vitro release studies showed controlled drug release which was influenced significantly by the properties and concentration of PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p <0.001) in clinical parameters such as gingival index, probing pocket depth, clinical attachment level, bleeding index and plaque index. The developed azithromycin smart gel system is a novel approach for the treatment of chronic periodontitis since it reduces the dose and side effects, bypasses the usual surgical procedures and improves patient compliance.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Double-Blind Method; Gels; Humans; In Vitro Techniques; Middle Aged; Periodontitis; Placebos

A validated instrument to assess the effects of chronic cough on health status in patients with chronic obstructive pulmonary disease (COPD) is currently not available. The Leicester Cough Questionnaire (LCQ) is a cough-specific health status questionnaire which is originally validated for a population of general patients presenting with chronic cough. We examined the psychometric performance of the LCQ in patients with COPD and chronic productive cough.. Concurrent validity, internal consistency, reproducibility and responsiveness were determined. The St. George's Respiratory Questionnaire (SGRQ) and the Short Form-36 (SF-36) were used as external criteria. Questionnaires were completed at the start of the study. After 2 and 12 weeks the LCQ was repeated, together with a global rating of change.. In total 54 patients were included. Concurrent validity analysis showed significant correlations between corresponding domains of the LCQ and the SGRQ (r(s) -0.31 to -0.60). Corresponding domains of the LCQ and the SF-36 showed weaker correlations (r(s) 0.04 to 0.41). Internal consistency was adequate for two of the three domains (Cronbach's α 0.74 - 0.86). Test-retest reliability in stable patients was high (intraclass correlation coefficients 0.79 - 0.93). The mean difference after two weeks was 0.73 (± 1.75). Responsiveness analysis indicated that the LCQ was able to detect changes after 12 weeks.. The LCQ is a valid, reliable, responsive instrument to measure health status in COPD patients with chronic productive cough.. ClinicalTrials.gov: NCT01071161.

Topics: Age Factors; Azithromycin; Chronic Disease; Cough; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Risk Factors; Sex Factors; Surveys and Questionnaires; Treatment Outcome

Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV(1)). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV(1) measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Double-Blind Method; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Syndrome; Time Factors; Transplantation, Homologous

In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo-controlled trial evaluating the efficacy of azithromycin (AZM) in CRS.. We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures.. Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either.. At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Endoscopy; Female; Humans; Macrolides; Male; Middle Aged; Rhinitis; Sinusitis; Time Factors; Treatment Outcome; Young Adult

Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA.. This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline.. The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups.. These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthritis, Reactive; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila pneumoniae; Chronic Disease; DNA, Bacterial; Double-Blind Method; Doxycycline; Drug Therapy, Combination; Female; Humans; Joints; Male; Middle Aged; Placebos; Prohibitins; Prospective Studies; Rifampin; Treatment Outcome

To examine subgingival microbiological changes in chronic periodontitis subjects receiving scaling and root planing (SRP) alone or with systemically administered azithromycin, metronidazole or a sub-antimicrobial dose of doxycycline.. Ninety-two periodontitis subjects were randomly assigned to receive SRP alone or combined with azithromycin, metronidazole or sub-antimicrobial dose doxycycline. Subgingival plaque samples taken at baseline, 2 weeks, and 3, 6, and 12 months were analyzed for 40 bacterial species using checkerboard DNA-DNA hybridization. Percentage of resistant species and percentage of sites harboring species resistant to the test antibiotics were determined at each time-point.. All treatments reduced counts of red complex species at 12 months, although no significant differences were detected among treatment groups for most species at all time-points. Both antibiotics significantly reduced counts of red complex species by 2 weeks. Percentage of resistant isolates increased in plaque samples in all adjunctive treatment groups, peaking at the end of administration, but returned to pretreatment levels by 12 months.. The significant reduction of red and orange complex species at 2 weeks in the subjects receiving SRP plus azithromycin or metronidazole may have contributed to a better clinical response in these treatment groups. Therapy did not appear to create lasting changes in the percentage of resistant isolates or sites harboring resistant species.

Topics: Adult; Anti-Infective Agents; Azithromycin; Chronic Disease; Dental Plaque; Dental Scaling; Doxycycline; Drug Resistance, Bacterial; Female; Humans; Male; Metronidazole; Middle Aged; Periodontitis; Single-Blind Method

To compare clinical changes occurring in chronic periodontitis subjects receiving SRP alone or with systemically administered azithromycin, metronidazole or a sub-antimicrobial dose of doxycycline.. 92 chronic periodontitis subjects were randomly assigned to receive SRP alone (N=23) or combined with 500 mg azithromycin per day for 3 days (N=25), 250 mg metronidazole tid for 14 days (N=24) or 20 mg doxycycline bid for 3 months (N=20). Gingival redness, bleeding on probing, suppuration, pocket depth and attachment level were measured at baseline and 3, 6 and 12 months post therapy. The significance of changes in clinical parameters within groups over time was sought using the Friedman test and among groups using ANCOVA or the Kruskal Wallis test.. All groups showed clinical improvements at 12 months, with subjects receiving adjunctive agents showing a somewhat better response. Sites with initial pocket depth > 6 mm showed significantly greater pocket depth reduction and greater attachment gain in subjects receiving metronidazole or azithromycin than subjects in the other groups. Some subjects showed attachment loss at 12 months in each group ranging from 15% to 39% of subjects in the SDD and SRP only groups respectively.. This study, demonstrated that periodontal therapy provides clinical benefits and that antibiotics provide a clinical benefit over SRP alone, particularly at initially deeper periodontal pockets.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Combined Modality Therapy; Dental Scaling; Doxycycline; Epidemiologic Methods; Female; Humans; Male; Metronidazole; Middle Aged; Periodontal Pocket; Periodontitis; Root Planing

One-stage full-mouth disinfection (FMD), in which full-mouth scaling and root planing (SRP) is performed with adjunctive use of chlorhexidine, was introduced in 1995. There have been several reports on the effectiveness of this treatment protocol. However, FMD was reported to induce pyrexia frequently. We examined the effects of full-mouth SRP in conjunction with azithromycin administered orally before SRP to control the number of bacteria. The purpose of this study was to compare the effects of full-mouth SRP using azithromycin with conventional SRP.. Thirty-four subjects (17 in the test group and 17 in the control group) with severe chronic periodontitis were selected. The subjects of the test group had azithromycin 3 days before full-mouth SRP. Clinical parameters (probing depth [PD], gingival index [GI], bleeding on probing [BOP], and gingival crevicular fluid [GCF]), total number of bacteria, and number of black pigment-producing rods (BPRs) were evaluated at baseline and 5, 13, and 25 weeks after baseline.. All clinical parameters improved in the test group more than in the control group. In the bacteriologic examination, the total number of bacteria did not change during the examination. In the test group, BPRs were not detected until 13 weeks. However, BPRs were detected in the control group by 13 weeks.. It was shown that full-mouth SRP using systemically administered azithromycin was a clinically and bacteriologically useful basic periodontal treatment for severe chronic periodontitis.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Bacteria, Anaerobic; Body Temperature; Chronic Disease; Colony Count, Microbial; Combined Modality Therapy; Dental Scaling; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Periodontal Index; Periodontal Pocket; Periodontitis; Preoperative Care; Root Planing

Chronic furunculosis is a recurrent staphylococcal abscess of the hair follicle. Besides ensuring personal hygiene, the management consists of long-term treatment with topical and systemic antibiotics.. An open-labeled, prospective study was conducted to assess the clinical and in vitro efficacy of azithromycin in the long-term suppressive treatment of chronic furunculosis.. Patients with a history of three or more episodes of furuncles were assigned to receive 12 weeks of suppressive treatment with azithromycin at a weekly dosage of 500 mg. In vitro susceptibility of azithromycin was evaluated with E-test. The primary efficacy parameter was complete absence of furuncles during the 3 months of azithromycin treatment. The secondary efficacy parameter was further absence of furuncles during the 3-month follow-up period.. At the end of 3 months of therapy, azithromycin was found to be effective in 19 (79.2%) of 24 patients; 18 of these patients remained in remission during the 3 months of follow-up. All of the strains were methicillin-sensitive. The results of the E-test showed that 15 of 18 strains (83.3%) were susceptible to azithromycin.. The results of this study indicate that azithromycin is an effective and safe alternative in the treatment of chronic furunculosis caused by methicillin-sensitive Staphylococcus aureus.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Drug Administration Schedule; Female; Furunculosis; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Severity of Illness Index; Staphylococcus aureus; Treatment Outcome

Along with conventional surgical therapy, systemic antibiotics may provide more effective treatment in smokers by targeting tissue-invasive bacteria. The aim of this randomized, placebo-controlled, double-masked clinical trial was to evaluate the adjunctive effects of systemic azithromycin (AZM) in combination with periodontal pocket reduction surgery in the treatment of chronic periodontitis in smokers.. Thirty patients with a greater than one pack/day smoking habit and generalized moderate to severe chronic periodontitis were randomized to the test (surgery plus 3 days of AZM, 500 mg) or control group (surgery plus 3 days of placebo). Full-mouth probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), plaque index, and wound healing indices (WHI) were assessed at baseline and at 2 weeks and 1, 3, and 6 months following surgical intervention. Plaque and gingival crevicular fluid were collected for trypsin-like enzyme activity (benzoyl-dl-arginine naphthylamine) and bone biomarker (crosslinked telopeptide of type I collagen [ICTP]) analyses, respectively, at baseline, 2 weeks, and 1, 3, and 6 months.. Surgical treatment of moderate (PD = 4 to 6 mm) and deep (PD > 6 mm) pockets significantly improved clinical parameters of treated and untreated teeth (CAL gain, PD reduction, and reduction of BOP). The additional use of AZM did not enhance this improvement nor did it promote reduction of ICTP levels. Compared to the control group, the test group had significantly better WHI scores at 1 month, significantly less GI at 2 weeks, and sustained reductions of red-complex bacteria with trypsin-like enzyme activity at 3 months. For non-surgery teeth, only the test group showed significant gains in overall CAL compared to baseline.. The findings of this pilot study demonstrated that in heavy smokers, adjunctive systemic AZM in combination with pocket reduction surgery did not significantly enhance PD reduction or CAL gain. However, the clinical value of adjunctive AZM may be appreciated by more rapid wound healing, less short-term gingival inflammation, and sustained reductions of periopathogenic bacteria. More expanded studies are recommended to better determine the clinical effects of adjunctive AZM in patients who smoke.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bacteroides; Benzoylarginine-2-Naphthylamide; Chronic Disease; Collagen Type I; Dental Plaque Index; Double-Blind Method; Female; Gingival Crevicular Fluid; Humans; Male; Middle Aged; Peptide Fragments; Peptides; Periodontal Index; Periodontitis; Pilot Projects; Porphyromonas gingivalis; Procollagen; Smoking; Treponema denticola; Wound Healing

Antibiotic therapy can be used in very specific periodontal treatment situations such as in refractory cases of periodontal disease found to be more prevalent in smokers. This study was designed to determine the efficacy of azithromycin (AZM) when combined with scaling and root planing (SRP) for the treatment of moderate to severe chronic periodontitis in smokers.. Thirty-one subjects were enrolled into a 6-month randomized, single-masked trial to evaluate clinical, microbial (using benzoyl- DL-arginine naphthylamine [BANA] assay), and gingival crevicular fluid (GCF) pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) levels in response to SRP alone or SRP + AZM. At baseline, patients who smoked > or =1 pack per day of cigarettes who presented with at least five sites with probing depths (PD) of > or =5 mm with bleeding on probing (BOP) were randomized into the test or control groups. At baseline and 3 and 6 months, clinical measurements (probing depth [PD], clinical attachment loss [CAL], and bleeding on probing [BOP]) were performed. GCF bone marker assessment (Ctelopeptide [ICTP] as well as BANA test analyses) were performed at baseline, 14 days, and 3 and 6 months.. The results demonstrated that both groups displayed clinical improvements in PD and CAL that were sustained for 6 months. Using a subject-based analysis, patients treated with SRP + AZM showed enhanced reductions in PD and gains in CAL at moderate (4 to 6 mm) and deep sites (>6 mm) (P <0.05). Furthermore, SRP + AZM resulted in greater reductions in BANA levels compared to SRP alone (P <0.05) while rebounds in BANA levels were noted in control group at the 6-month evaluation. No statistically significant differences between groups on mean BOP and ICTP levels during the course of the study were noted.. The utilization of AZM in combination with SRP improves the efficacy of non-surgical periodontal therapy in reducing probing depth and improving attachment levels in smokers with moderate to advanced attachment loss.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Benzoylarginine-2-Naphthylamide; Chronic Disease; Collagen Type I; Dental Scaling; Female; Follow-Up Studies; Gingival Crevicular Fluid; Gingival Hemorrhage; Humans; Male; Middle Aged; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Pocket; Periodontitis; Procollagen; Root Planing; Single-Blind Method; Smoking; Treatment Outcome

Topics: Adult; Aged; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Prostatitis; Treatment Outcome

Chlamydia pneumoniae (Cpn) is a common respiratory pathogen with a biphasic replicative cycle and has a tendency to cause chronic infections. Azithromycin is commonly used for the treatment of Cpn infections, but little is known about the optimal dose and duration of therapy. In this prospective double-blind, randomized study the effects of azithromycin and placebo were compared regarding longstanding airway and/or pharyngeal symptoms in patients with chronic Cpn infection. Further, effects on antibody titres and lung function were assessed. 103 patients were treated with either azithromycin 500 mg daily for 5 d, repeated 3 times with a 23-d interval, or placebo. Patients were examined 4 months and 1 y after completed treatment. Evaluation of symptoms showed general improvement and less hawking in patients treated with azithromycin compared to placebo after 4 months, but there was no sustained difference 1 y after completed treatment. The antibody titres remained stable, and there was no influence on lung function. Adverse events, primarily gastrointestinal, were more frequently reported with azithromycin than placebo. In conclusion, azithromycin was effective for reduction of respiratory symptoms in patients with chronic Cpn infection, but prolonged intermittent treatment with high doses did not eradicate the chronic infection.

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunoglobulin A; Immunoglobulin G; Male; Middle Aged; Patient Compliance; Respiratory Function Tests; Treatment Outcome

A total of 89 patients, (>18 years), with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method and/or by isolation, McCoy culture and Lugol stain in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or ciprofloxacin 500 mg b.i.d. for 20 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. Significantly higher eradication (36/45: 17/44; P=0.0002) and a significantly higher clinical cure (31/45: 15/44; P=0.0021) were achieved in the group of patients treated with azithromycin than in the ciprofloxacin group.

Topics: Adolescent; Adult; Aged; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Ciprofloxacin; Humans; Male; Middle Aged; Prostate; Prostatitis

Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF.. To determine if an association between azithromycin use and pulmonary function exists in patients with CF.. A multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States.. Of the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV1) of 30% or more. Participants were stratified by FEV1 (> or =60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center.. The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight > or =40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets.. Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.. The azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV1 at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P =.009). Nausea occurred in 17% more participants in the azithromycin group (P =.01), diarrhea in 15% more (P =.009), and wheezing in 13% more (P =.007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P =.03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P =.02).. Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Chronic Disease; Cystic Fibrosis; Double-Blind Method; Female; Forced Expiratory Flow Rates; Hospitalization; Humans; Interleukin-8; Male; Pancreatic Elastase; Proportional Hazards Models; Pseudomonas Infections; Quality of Life; Treatment Outcome

A total of 123 patients, older than 18 years of age, with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or clarithromycin 500 mg b.i.d. for 15 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. In the group of patients with chronic chlamydial prostatitis the eradication rates (azithromycin 37/46, clarithromycin 36/45) and the clinical cure rates (azithromycin 32/46, clarithromycin 32/45) were not significantly different with regards to the administered drug (p > 0.05). In the group of patients with asymptomatic chlamydial prostatitis the eradication rates (azithromycin 11/16, clarithromycin 10/15) were not significantly different with regards to the administered drug (p = 1.00, OR = 1.1).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Clarithromycin; Dose-Response Relationship, Drug; Humans; Male; Maximum Tolerated Dose; Middle Aged; Prospective Studies; Prostatitis; Treatment Outcome

53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospective, multicentre, double-blind, placebo-controlled study. The chronic bronchitis was staged by forced expiratory volume of the 1st second (FEV(1)) measured in the infection-free interval prior to the current episode and had to be between 35 and 75% for the predicted value. Patients were randomly assigned to receive newer macrolide antibiotics plus either Esberitox N or placebo. Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days. The baseline-adjusted means for FEV(1) (%) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group (p = 0.0303). For FEV(1) the difference between the two treatment groups was 267 ml (p = 0.0499). The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group. The treatment was well tolerated; no serious adverse events were documented. In conclusion, comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient. Apparently, therapy with Esberitox N leads to a faster recovery from this severe bacterial infection, possibly via preventing an impairment of the host's immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics.

Topics: Adjuvants, Immunologic; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis, Chronic; Chronic Disease; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Humans; Lung Diseases, Obstructive; Pilot Projects; Plant Extracts; Roxithromycin; Time Factors

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to azithromycin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) of suspected bacterial origin. Between October 1998 and April 1999, 567 patients with AECB were enrolled at 37 centers across the United States and Canada of which 280 (49%) had acute bacterial exacerbation of chronic bronchitis (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administered once daily for 5 days or azithromycin for 5 days (500 mg qd x 1, then 250 mg qd x 4). For the purpose of study blinding, all patients received encapsulated tablets. The main outcome measure was clinical response at the test-of-cure visit (14-21 days post-therapy). Secondary measures included bacteriologic response and a time-course of bacteriological eradication (one center only). Three patient populations were analysed for efficacy: clinically-valid, microbiologically-valid (i.e. those with a pretherapy pathogen), and intent-to-treat (i.e. received at least one dose of study drug). For the efficacy-valid group, clinical response at the test-of-cure visit was 88% for patients in each treatment group. In 237 microbiologically-valid patients, corresponding clinical resolution rates were 88% for 5-day moxifloxacin vs. 86% for 5-day azithromycin. Bacteriological eradication rates at the end of therapy were 95% for 5-day moxifloxacin and 94% for the azithromycin group. Corresponding eradication rates at the test-of-cure visit were 89% and 86%, respectively. Of note, eradication rates at test-of-cure for Haem. philos influenzae and H. parainfluenzae for moxifloxacin were 97% and 88% compared to 83% and 62% respectively for azithromycin. Among 567 intent-to-treat patients (283 moxifloxacin and 284 azithromycin), drug-related events were reported for 22% and 17%, respectively. Diarrhea and nausea were the most common drug-related events reported in each treatment group. Moxifloxacin 400 mg once daily for 5 days was found to be clinically and bacteriologically equivalent to 5-day azithromycin for the treatment of AECB of proven bacterial etiology. Given its excellent in-vitro activity, especially against antibiotic-resistant respiratory pathogens, and its acceptable safety profile, moxifloxacin should be considered an effective alternative therapy for patients wi

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Double-Blind Method; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Multicenter Studies as Topic; Prospective Studies; Quinolines

To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS.. Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency.. Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose.. Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Chronic Disease; Cryptosporidiosis; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Treatment Outcome

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.

Topics: Acetylcysteine; Administration, Intranasal; Adolescent; Adult; Agammaglobulinemia; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Ataxia Telangiectasia; Azithromycin; Beclomethasone; Blood Proteins; Child; Child, Preschool; Chronic Disease; Common Variable Immunodeficiency; Eosinophil Granule Proteins; Ethmoid Sinusitis; Female; Frontal Sinusitis; Glucocorticoids; Humans; Immunization, Passive; Interleukin-8; Lymphoproliferative Disorders; Magnetic Resonance Imaging; Male; Nasal Lavage Fluid; Paranasal Sinuses; Radiography; Ribonucleases; Sinusitis; Tumor Necrosis Factor-alpha

In vitro study of the antibacterial activity of macrolide antibiotics azitromycin (sumamed), midicamycin (macropen), roxitromycin (rulide), and erythromycin demonstrated their high activity towards clinical strains of bacteroids, fusobacteria, peptostreptococci, streptococci, and corynebacteria. These antibiotics were effective in the treatment of 62 adult patients with severe and moderate generalized periodontitis. Rulide and sumamed were the most effective, macropen and erythromycin were inferior to them.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Antifungal Agents; Azithromycin; Chronic Disease; Drug Therapy, Combination; Erythromycin; Humans; Leucomycins; Middle Aged; Nystatin; Periodontitis; Roxithromycin

Some diseases previously believed to be noninfectious, eg, peptic ulcer disease, are now known to be caused by chronic infection. Recently, chronic Chlamydia pneumoniae infection has been suggested as a cause for adult-onset asthma. The purpose of this study was to determine whether antichlamydial treatment would affect the natural history of this disease.. An open-label, before-after treatment trial was performed in a community-based, primary care office. Forty-six patients (mean age 47.7 years; range 17 to 78) with moderate to moderately severe, stable, chronic asthma were treated a median of 4 weeks (range 3 to 9) with oral doxycycline (100 mg twice daily), azithromycin (1000 mg once weekly), or erythromycin (1000 mg daily). Post-treatment pulmonary function and asthma symptoms were compared with baseline values. Follow-up was an average of 6 months (range 1.5 to 36) post-treatment.. Four patients with C pneumoniae respiratory tract infection developed chronic asthma, which disappeared after treatment in each case. Of the remaining 42 seroreactive patients who were treated a mean of 6 years after the development of chronic asthma, one half had either complete remission or major clinical improvement (3 and 18 patients, respectively). This improvement was significantly more likely to occur in patients with early disease (P = .01) and before the development of fixed obstruction (P < .01).. Antimicrobial therapy appeared to "cure" or significantly improve asthma in approximately one half of treated adults, and the response pattern was consistent with chlamydial pathogenesis. C pneumoniae infection in asthma may be clinically important and should be investigated further.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Asthma; Azithromycin; Child; Chlamydia Infections; Chlamydophila pneumoniae; Chronic Disease; Doxycycline; Erythromycin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Respiratory Function Tests; Time Factors; Treatment Outcome

An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Sputum

Topics: Azithromycin; Chlamydia Infections; Chronic Disease; Female; Female Urogenital Diseases; Humans; Male; Male Urogenital Diseases; Syphilis

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Bronchitis; Chronic Disease; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Middle Aged; Pneumonia; Prospective Studies; Roxithromycin; Treatment Outcome

The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis.

Topics: Aged; Amoxicillin; Azithromycin; Bronchitis; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged

Asthma is the most frequent chronic airway illness in preschool children and is difficult to diagnose due to the disease's heterogeneity. This study aimed to investigate different machine learning models and suggested the most effective one to classify two forms of asthma in preschool children (predominantly allergic asthma and non-allergic asthma) using a minimum number of features.. After pre-processing, 127 patients (70 with non-allergic asthma and 57 with predominantly allergic asthma) were chosen for final analysis from the Frankfurt dataset, which had asthma-related information on 205 patients. The Random Forest algorithm and Chi-square were used to select the key features from a total of 63 features. Six machine learning models: random forest, extreme gradient boosting, support vector machines, adaptive boosting, extra tree classifier, and logistic regression were then trained and tested using 10-fold stratified cross-validation.. Among all features, age, weight, C-reactive protein, eosinophilic granulocytes, oxygen saturation, pre-medication inhaled corticosteroid + long-acting beta2-agonist (PM-ICS + LABA), PM-other (other pre-medication), H-Pulmicort/celestamine (Pulmicort/celestamine during hospitalization), and H-azithromycin (azithromycin during hospitalization) were found to be highly important. The support vector machine approach with a linear kernel was able to diffrentiate between predominantly allergic asthma and non-allergic asthma with higher accuracy (77.8%), precision (0.81), with a true positive rate of 0.73 and a true negative rate of 0.81, a F1 score of 0.81, and a ROC-AUC score of 0.79. Logistic regression was found to be the second-best classifier with an overall accuracy of 76.2%.. Predominantly allergic and non-allergic asthma can be classified using machine learning approaches based on nine features.. Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Topics: Asthma; Azithromycin; Budesonide; Child, Preschool; Chronic Disease; Hospitalization; Humans; Machine Learning

Previous in vitro transcriptomic profiling suggests azithromycin exerts its effects in patients with chronic rhinosinusitis (CRS) via modulation of type 1 inflammation and restoration of epithelial barrier function. We wished to verify these postulated effects using in vitro models of epithelial repair and in vivo transcriptional profiling.. Functional effects of azithromycin in CRS were verified using in vitro models of wounding. The mechanism of the effect of azithromycin was assessed in vivo using transcriptomic profiling.. Academic medical center.. Effects of azithromycin on the speed of epithelial repair were verified in a wounding model using primary nasal epithelial cells (pNEC) from CRS patients. Nasal brushings collected pre-and posttreatment during a placebo-controlled trial of azithromycin for CRS patients unresponsive to surgery underwent transcriptomic profiling to identify implicated pathways.. Administration of azithromycin improved the wound healing rates in CRS pNECs and prevented the negative effect of Staphylococcus aureus on epithelial repair. In vivo, response to azithromycin was associated with downregulation in pathways of type 1 inflammation, and upregulation of pathways implicated in the restoration of the cell cycle.. Restoration of healthy epithelial function may represent a major mode of action of azithromycin in CRS. In vitro models show enhanced epithelial repair, while in vivo transcriptomics shows downregulation of pathways type 1 inflammation accompanied by upregulation of DNA repair and cell-cycle pathways. The maximal effect in patients with high levels of type 1-enhanced inflammation suggests that azithromycin may represent a novel therapeutic option for surgery-unresponsive CRS patients.

Topics: Azithromycin; Chronic Disease; Humans; Inflammation; Nasal Mucosa; Nasal Polyps; Rhinitis; Sinusitis

Protracted bacterial bronchitis (PBB) causes chronic wet cough for which seasonal azithromycin is increasingly used to reduce exacerbations. We investigated the impact of seasonal azithromycin on antimicrobial resistance and the nasopharyngeal microbiome. In an observational cohort study, 50 children with PBB were enrolled over two consecutive winters; 25/50 at study entry were designated on clinical grounds to take azithromycin over the winter months and 25/50 were not. Serial nasopharyngeal swabs were collected during the study period (12-20 months) and cultured bacterial isolates were assessed for antimicrobial susceptibility. 16S rRNA-based sequencing was performed on a subset of samples. Irrespective of azithromycin usage, high levels of azithromycin resistance were found; 73% of bacteria from swabs in the azithromycin group vs. 69% in the comparison group. Resistance was predominantly driven by azithromycin-resistant

Topics: Anti-Bacterial Agents; Azithromycin; Bacteria; Bacterial Infections; Bronchitis, Chronic; Child; Chronic Disease; Cough; Drug Resistance, Bacterial; Erythromycin; Humans; Microbiota; RNA, Ribosomal, 16S; Seasons; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Azithromycin; Chronic Disease; Hematopoietic Stem Cell Transplantation; Humans; Metabolic Networks and Pathways; Recurrence

Following publication of the ALLOZITHRO trial, the FDA released a safety announcement warning that azithromycin should not be given long-term to prevent BOS in patients with a blood or lymph cancer who have undergone allogeneic HSCT. Our site typically initiated azithromycin when patients were diagnosed with BOS post-transplant rather than empirically as prevention. The purpose of our study was to discern whether the use of azithromycin at the time of diagnosis of BOS increased risk of disease relapse in patients who received an allogeneic HSCT for malignant disease. We retrospectively reviewed 432 patients in 3 cohorts: Cohort (1) patients who received greater than or equal to 2 weeks of azithromycin therapy (n = 98); Cohort (2) patients who received azithromycin therapy for less than 2 weeks (n = 63); and Cohort (3) patients who never received azithromycin therapy (n = 271). Neither patients in Cohort 1 (HR 0.44; 95% CI, 0.12-1.53, P = 0.19) nor Cohort 2 (HR 0.66; 95% CI, 0.2-2.19, P = 0.49) were associated with an increased risk of relapse when compared to those who had never received azithromycin. Our data indicate that the prolonged use of azithromycin after allogeneic HSCT is not associated with an increased rate of hematologic relapse.

Topics: Azithromycin; Chronic Disease; Hematopoietic Stem Cell Transplantation; Humans; Recurrence; Retrospective Studies

Topics: Anti-Inflammatory Agents; Azithromycin; Betacoronavirus; Cells, Cultured; Chronic Disease; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Down-Regulation; Host-Pathogen Interactions; Humans; Interleukin-1beta; Male; Membrane Proteins; Nasal Mucosa; Pandemics; Pilot Projects; Pneumonia, Viral; Rhinitis; SARS-CoV-2; Serine Endopeptidases; Serine Proteases; Signal Transduction; Sinusitis

Azithromycin prophylaxis (AP) in lung transplant recipients has been shown to reduce the composite end-point of death or chronic lung allograft dysfunction (CLAD) onset but without a clear effect on overall survival. Our program began using AP in 2010. We sought to evaluate the association between AP and survival and the risk of CLAD and baseline lung allograft dysfunction (BLAD).. We studied double lung recipients transplanted between 2004 and 2016. We defined AP as chronic use of azithromycin initiated before CLAD onset. We analyzed the association between AP and death or retransplant using Cox regression with adjustment for potential confounders. We further used Cox and logistic models to assess the relationship between AP and post-transplant CLAD onset and BLAD, respectively.. A total of 445 patients were included, and 344 (77%) received AP (median time from transplant: 51 days). Patients receiving AP were more likely to receive induction with interleukin-2 receptor antagonists (57% vs 35%; p < 0.001). AP was associated with improved survival (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42-0.82; p = 0.0020) in our fully adjusted model, with a reduced adjusted risk of BLAD (odds ratio: 0.53; 95% CI: 0.33-0.85; p = 0.0460) but no clear reduction in the adjusted risk of CLAD (HR: 0.69; 95% CI: 0.47-1.03; p = 0.0697).. AP is associated with improved survival after lung transplantation, potentially through improved baseline function. These findings build on prior trial results and suggest that AP is beneficial for lung transplant recipients.

Topics: Allografts; Anti-Bacterial Agents; Azithromycin; Biopsy; Bronchiolitis Obliterans; Chronic Disease; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Lung; Lung Transplantation; Male; Middle Aged; Postoperative Care; Primary Graft Dysfunction; Retrospective Studies; Risk Factors; Transplant Recipients; Treatment Outcome

Adult patients with chronic productive cough of unknown cause are commonly seen in respiratory clinics. We have previously described a subgroup of these patients who have a short-lived response to standard antibiotic treatment but a prolonged response to 3 months of low-dose azithromycin therapy.. This observational study describes the physiological, radiological and pathological features of this patient cohort along with their response to a 12-week open-label trial of 250 mg azithromycin thrice weekly.. A total of 30 subjects with a mean age of 57 were recruited. The majority demonstrated airway dilatation on high-resolution computed tomography (HRCT) scan without evidence of established bronchiectasis (n = 21) and non-specific chronic inflammatory changes on bronchial biopsy (n = 15/17). Twenty-nine subjects completed 3 months of azithromycin with a significant improvement in median Leicester Cough Questionnaire (LCQ) score (-6.3 points, P < 0.00001), reduction in median 24-h sputum volume (-5.8 mL, P = 0.0003) and improvement in sputum colour (P = 0.003). Patients responsive to azithromycin (n = 22) demonstrated neutrophilic or paucigranulocytic airway inflammation, whereas five subjects with eosinophilic airways inflammation did not respond symptomatically to azithromycin.. We describe a cohort of patients with chronic productive cough not adequately described by existing disease labels whose symptoms responded well to low-dose azithromycin. Many of the features are similar to the paediatric condition protracted bacterial bronchitis.

Topics: Anti-Bacterial Agents; Azithromycin; Chronic Disease; Cough; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Inflammation; Male; Middle Aged; Neutrophils; Sputum; Tomography, X-Ray Computed; Treatment Outcome

Chlamydia infection remains the leading sexually-transmitted bacterial infection worldwide, causing damaging sequelae such as tubal scarring, infertility and ectopic pregnancy. As infection is often asymptomatic, prevention via vaccination is the optimal strategy for disease control. Vaccination strategies aimed at preventing bacterial infection have shown some promise, although these strategies often fail to prevent damaging inflammatory pathology when Chlamydia is encountered. Using a murine model of Chlamydia muridarum genital infection, we employed two established independent models to compare immune responses underpinning pathologic development of genital Chlamydia infection. Model one uses antibiotic treatment during infection, with only early treatment preventing pathology. Model two uses a plasmid-cured variant strain of C. muridarum that does not cause pathologic outcomes like the plasmid-containing wild-type counterpart. Using these infection models, contrasted by the development of pathology, we identified an unexpected role for macrophages. We observed that mice showing signs of pathology had greater numbers of activated macrophages present in the oviducts. This may have been due to early differences in macrophage activation and proinflammatory signaling leading to persistent or enhanced infection. These results provide valuable insight into the cellular mechanisms driving pathology in Chlamydia infection and contribute to the design and development of more effective vaccine strategies for protection against the deleterious sequelae of Chlamydia infection of the female reproductive tract.

Topics: Animals; Azithromycin; Chlamydia Infections; Chlamydia muridarum; Chronic Disease; Cytokines; Drug Resistance, Bacterial; Fallopian Tubes; Female; Gene Expression Regulation; Inflammation; Inflammation Mediators; Macrophages; Mice, Inbred BALB C; Oviducts

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

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.

Topics: Adult; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Female; Germany; Humans; Lung; Lung Transplantation; Male; Middle Aged; Primary Graft Dysfunction; Retrospective Studies; Risk Factors; Survival Analysis; Tidal Volume; Transplantation, Homologous

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Physiological Phenomena; Child; Chronic Disease; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Electrophysiologic Techniques, Cardiac; Female; Humans; Long QT Syndrome; Male; Respiratory Tract Diseases; Spain; Treatment Outcome

Of the non-tuberculous mycobacteria, Mycobacterium abscessus is particularly refractory to antimicrobial therapy and new agents with activity against these pathogens are urgently needed. The screening of candidate antimicrobial agents against M. abscessus requires a relevant and reproducible animal model of chronic infection. Granulocyte-macrophage colony-stimulating factor knockout (GM-CSF KO) mice were used to develop a new animal model of chronic pulmonary M. abscessus infection that can be used for preclinical efficacy testing of antimicrobial drugs.. GM-CSF KO mice were infected with a clinical isolate of M. abscessus via intrapulmonary aerosol delivery using a microsprayer device. The clinical condition, histology and cfu of M. abscessus-infected GM-CSF KO mice were evaluated over a period of 4 months. Mice were treated with azithromycin (100 mg/kg) by oral gavage and the clinical condition, histology and bacterial burden was determined after 2 weeks of treatment.. We show that pulmonary infection of GM-CSF KO mice with M. abscessus results in a chronic pulmonary infection that lends itself to preclinical testing of new antimicrobial drugs against this bacterium. Azithromycin treatment of M. abscessus-infected GM-CSF KO mice resulted in a lower bacterial burden in the lungs and spleen, weight gain and significant improvement in lung pathology.. Intrapulmonary aerosol infection of GM-CSF KO mice with M. abscessus is a useful animal model for studying pathogenesis as well as pre-clinical testing of new compounds against M. abscessus in acute or chronic phases of infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Load; Chronic Disease; Disease Models, Animal; Drug Evaluation, Preclinical; Granulocyte-Macrophage Colony-Stimulating Factor; Histocytochemistry; Lung; Mice; Mice, Knockout; Mycobacterium; Mycobacterium Infections; Pneumonia, Bacterial; Spleen

Although survival after lung transplantation has improved significantly during the last decade, chronic rejection is thought to be the major cause of late mortality. The physiologic hallmark of chronic rejection has been a persistent fall in forced expiratory volume in 1 second associated with an obstructive ventilatory defect, for which the term bronchiolitis obliterans syndrome (BOS) was defined to allow a uniformity of description and grading of severity throughout the world. Although BOS was generally thought to be irreversible, recent evidence suggests that some patients with BOS may respond to azithromycin with > 10% improvement in their forced expiratory volume in 1 second. In addition, a restrictive form of chronic rejection has recently been described that does not fit the strict definition of BOS as an obstructive defect. Hence, the term chronic lung allograft dysfunction (CLAD) has been introduced to cover all forms of graft dysfunction, but CLAD has yet to be defined. We propose a definition of CLAD and a flow chart that may facilitate recognition of the different phenotypes of CLAD that can complicate the clinical course of lung transplant recipients.

Topics: Allografts; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Forced Expiratory Volume; Graft Rejection; Humans; Lung; Lung Transplantation; Phenotype; Terminology as Topic

Acute exacerbation of chronic fibrosing interstitial pneumonia (AE-CFIP) is an often fatal condition with no established treatment. Recently, macrolides were found to be beneficial in cases of acute lung injury.. To examine the clinical effectiveness and safety of intravenous azithromycin in patients hospitalized for AE-CFIP.. A prospective, open-label study with historical controls was conducted. Twenty consecutive patients with AE-CFIP received azithromycin. They were compared with a historical cohort treated with fluoroquinolone (n = 56). All patients received high-dose steroid pulse therapy. The primary end point was mortality at 60 days. The secondary end point was safety of intravenous azithromycin in patients with AE-CFIP. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to investigate the relationship between azithromycin use and survival time.. Mortality was significantly lower in the patients treated with azithromycin than in those treated with fluoroquinolone (mortality rate at 60 days: 20 vs. 69.6%, p < 0.001; median survival time: not reached vs. 29.5 days, p < 0.001). The IPTW adjusted hazard of mortality at 60 days in patients receiving azithromycin was 0.17 (95% CI 0.05-0.61). No serious adverse events were observed.. Azithromycin was associated with improved outcomes in patients with AE-CFIP. Further studies are needed to verify this finding (Clinical trial JMA-IIA00095).

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Disease Progression; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Japan; Lung Diseases, Interstitial; Male; Prospective Studies; Steroids; Survival Analysis; Treatment Outcome

Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Chronic Disease; Humans

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week(-1)) with ciprofloxacin at the rate of 750 mg day(-1) for 4 weeks rather than at 500 mg day(-1) for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Chronic Disease; Ciprofloxacin; Cohort Studies; Drug Therapy, Combination; Fluoroquinolones; Humans; Macrolides; Male; Prostatitis; Retrospective Studies

Mycoplasma pneumoniae has rarely been reported in renal transplant recipients. We present the case of a 10-yr-old boy with a six-month history of chronic cough, recurrent pyrexia, and weight loss three yr after RTx. The patient's post-transplant course was complicated by recurrence of NS that resolved with plasmapheresis and PTLD, which was successfully treated with an anti-CD20 monoclonal antibody. Chest X-ray showed a round mass-like lesion in the left upper lobe; MRT, PET, and bronchoscopy ruled out a PTLD. BAL fluid revealed M. pneumoniae-DNA. A three-wk course of macrolide therapy induced rapid recovery. We conclude that M. pneumoniae infection should be considered in immunosuppressed patients with long-lasting respiratory complaints and fever of unknown origin. Antibiotic treatment should be given for a minimum of three wk.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chronic Disease; Humans; Kidney Transplantation; Male; Pneumonia, Mycoplasma

Topics: Administration, Oral; Anti-Inflammatory Agents; Azithromycin; Child; Chronic Disease; Humans; Iridocyclitis; Male; Recurrence; Retreatment; Siblings

Current pharmacologic treatments for gastroparesis have been disappointing due to the limited options available. Erythromycin ethylsuccinate is a potent prokinetic agent that stimulates gastric emptying. Recently, erythromycin has been linked to the occurrences of sudden cardiac death due to QT prolongation. Azithromycin is similar to erythromycin in structure but does not have significant drug-drug interactions as seen with erythromycin.. This study aims to determine whether azithromycin stimulates antral activity in patients with chronic gastrointestinal pain and refractory gastroparesis.. Small bowel manometric data on 30 patients undergoing clinical evaluation for chronic digestive problems or documented refractory gastroparesis were reviewed. Antral activity was measured after infusion of erythromycin 250 mg intravenous and azithromycin (500 or 250 mg intravenous) given at different intervals during the small bowel manometry. The parameters measured included the total duration of effect, mean amplitude of antral contractions, duration of the highest antral contraction phase, number of cycles per minute, and the motility index.. Comparison of erythromycin and azithromycin at similar doses showed a similar positive effect on antral activity. However, comparison of erythromycin and azithromycin at the higher dose of 500 mg showed that the mean amplitude, duration of antral activity, and motility index were significantly increased with azithromycin (P < 0.05).. Azithromycin stimulates antral activity similar to erythromycin and moreover has a longer duration of effect. However, unlike erythromycin, azithromycin does not have significant drug-drug interactions and maybe a potential new medication for the treatment of gastroparesis and gastrointestinal dysmotility.

Topics: Abdominal Pain; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Erythromycin Ethylsuccinate; Female; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans; Male; Manometry; Middle Aged; Pyloric Antrum

Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment.. CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment.. 70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae.. Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Denmark; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Infant; Long-Term Care; Microbial Sensitivity Tests; Middle Aged; Moraxella catarrhalis; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sputum; Staphylococcus aureus; Streptococcus pneumoniae; Young Adult

We examined a total of 1014 patients over 18 years of age; 252 with urethritis and 762 with chronic prostatitis syndrome. the mean age of patients with urethritis was 32.7 and with prostatitis syndrome 37.6 years. Clinical symptoms of urethritis were present from a few days to several months. in patients with chronic prostatitis syndrome, symptoms were present for at least 3 months. Chlamydia trachomatis alone was confirmed in 26 (10%) and in combination with Ureaplasma urealyticum in 6 (2%) patients with urethritis. in 171 (68%) patients with urethritis neither C. trachomatis nor U. urealyticum or Mycoplasma hominis were found. C. trachomatis alone was confirmed in 70 (9%), and in combination with other microorganisms in 7 (1%) patients with chronic prostatitis syndrome. in Croatia, the frequency of chronic chlamydial prostatitis has not significantly changed in the last 10 years, while the frequency of infections among adolescents decreased. the recommended regimen for acute chlamydial urethritis in Croatia is azithromycin 1.0 g as a single dose, and a total dose of 4-4.5 g azithromycin for chronic chlamydial prostatitis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Croatia; Humans; Male; Prostatitis; Urethritis

Trachoma, a major cause of blindness in some of the world's poorest countries, results from repeated or chronic eye infections with Chlamydia trachomatis.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Blindness; Child; Child, Preschool; Chronic Disease; Corneal Opacity; Developing Countries; Eye Infections, Bacterial; Global Health; Humans; Infant; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Tetracycline; Trachoma; World Health Organization

We tested the efficacy of azithromycin ophthalmic solution for the treatment of chronic mixed anterior blepharitis. The findings suggest that patients with chronic mixed anterior blepharitis can be more effectively treated with azithromycin ophthalmic solution than erythromycin ophthalmic ointment. Patients treated with azithromycin ophthalmic solution show an extraordinary clinical response with shorter treatment duration.

Topics: Aged; Anterior Eye Segment; Anti-Bacterial Agents; Azithromycin; Blepharitis; Chronic Disease; Erythromycin; Eye Infections, Bacterial; Female; Humans; Male; Ophthalmic Solutions; Prospective Studies; Treatment Outcome

Babesia gibsoni is a protozoan parasite of dogs worldwide yet both an effective treatment and a reliable method for detecting subclinical cases of this emerging infection remain elusive. Experimental B. gibsoni infections were established in vivo to investigate the efficacy of combined atovaquone and azithromycin drug therapy and to determine the detection limits of a nested-PCR, IFAT and microscopy during various stages of infection. While atovaquone and azithromycin produced a reduction in parasitaemia, it did not eliminate the parasite and drug resistance appeared to develop in one dog. Polymerase chain reaction was found to be most useful in detecting infection in the pre-acute and acute stages, while IFAT was most reliable during chronic infections. Microscopy is suggested to be only effective for detecting acute stage infections. This study also describes the detection of B. gibsoni in tissue samples during chronic infections for the first time, suggesting possible sequestration of this parasite.

Topics: Acute Disease; Animals; Anti-Infective Agents; Antibodies, Protozoan; Atovaquone; Azithromycin; Babesia; Babesiosis; Chronic Disease; DNA, Protozoan; Dog Diseases; Dogs; Drug Resistance; Female; Fluorescent Antibody Technique; Parasitemia; Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; Azithromycin; Blindness; Child, Preschool; Chronic Disease; Diagnosis, Differential; Female; Humans; Inflammation; Population Surveillance; Prevalence; Public Health; Trachoma; World Health Organization

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Protozoan; Antimalarials; Atovaquone; Azithromycin; Babesiosis; Chronic Disease; Erythrocyte Inclusions; False Positive Reactions; Female; Humans; Immunoglobulin G; Immunoglobulin M; Platelet Count; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Splenectomy

The intracellular bacterium Chlamydophila pneumoniae (Cp) was infrequently found in nasopharynx and lacking in biopsies from the middle turbinate in chronic rhinosinusitis (CRS) patients. Compared with healthy controls, patients suffering from CRS had significantly higher and more prevalent antibody titers to Cp. However, an association between CRS and Cp could not be established.. To study the prevalence of Cp in CRS patients and in healthy controls to determine if an association exists between Cp and CRS.. PCR against Cp was run on middle turbinate biopsies and on throat and nasopharyngeal swabs from 25 CRS patients and from 10 healthy controls. Serum samples were tested for Cp-specific antibodies by the microimmunofluorescence method. Patients that tested positive for Cp or had high antibody titers were treated with antibiotics.. Cp was found in nasopharyngeal samples from two patients but from none of the controls. Neither patients nor controls had Cp in biopsies from the middle turbinate. Antibody titers against Cp were significantly higher and more prevalent in patients than in controls. Seventeen patients were treated with antibiotics but only four of them recovered from sinusitis symptoms during the 2-year follow-up.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibodies; Azithromycin; Case-Control Studies; Chlamydophila pneumoniae; Chronic Disease; DNA, Bacterial; Doxycycline; Female; Humans; Immunoglobulins; Male; Middle Aged; Nasal Mucosa; Nasopharynx; Sinusitis; Turbinates

In cystic fibrosis (CF), chronic endobronchial infection with Pseudomonas aeruginosa is a serious complication. Macrolides can increase lung function and weight in patients, and reduce exacerbations.. In 2001, we introduced long-term, low-dose azithromycin (AZ) treatment as an integral part of our routine treatment of these patients. Our study is an observational cohort study of all CF patients with chronic P. aeruginosa infection in our CF center comparing clinical parameters of the patients 12 months prior to treatment with the same values during 12 months of treatment.. 45 patients (27 men, median age 29 years) completed 1-year treatment. Median weight increased from 63.1 kg in the pre-treatment period to 63.9 kg during treatment (p=0.01). Median slope of decline in lung function increased from pre-treatment FEV1 -4.1% and FVC -3.0% to +0.8% (p<0.001) and +1.6% (p=0.01), respectively. 90% of sputum samples contained mucoid P. aeruginosa before treatment, decreasing to 81% during treatment (p=0.003). Median CRP decreased from 6.2 mmol/l to 5.8 mmol/l (ns).. Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Cystic Fibrosis; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Observation; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum; Treatment Outcome

To evaluate whether antimicrobial chemotherapy prevents acceleration of atherosclerotic lesion development induced by infection with Chlamydia pneumoniae.. ApoE-deficient mice which develop hyperlipidaemia and atherosclerosis spontaneously were inoculated intranasally with C. pneumoniae. Animals were treated with azithromycin for 6 weeks after the third inoculation and the atherosclerotic lesion areas in the aortic sinus were measured by computer-assisted morphometry.. At 12 weeks post-infection, infected untreated animals developed significantly larger lesion areas compared with sham-inoculated controls (8.7 x 10(4)+/-2.3 x 10(4) microm(2) versus 5.6 x 10(4)+/-2.4 x 10(4) microm(2)). However, there were no differences in lesion size of infected mice treated with azithromycin in comparison with untreated infected controls (11.0 x 10(4)+/-3.0 x 10(4) microm(2) versus 8.7 x 10(4)+/-2.3 x 10(4) microm(2)).. Antibiotic treatment against C. pneumoniae has no beneficial effects on hyperlipidaemia-induced atherosclerosis accelerated by C. pneumoniae in a mouse model.

Topics: Animals; Anti-Bacterial Agents; Apolipoproteins E; Arteriosclerosis; Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Chronic Disease; Male; Mice

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

Longterm macrolide therapy has been reported to be effective in treating chronic lower respiratory tract infections (CLRTIs). In this context, erythromycin and clarithromycin are usually used for this purpose. However, refractory cases are occasionally encountered, thereby indicating a major problem pending. In the present study, we administered azithromycin to three patients with CLRTIs whose clinical course had been unsatisfactory with longterm therapy of either erythromycin or clarithromycin. Following longterm therapy with azithromycin, both the incidence of acute exacerbations and the sputum volume were decreased. A significant change in the sputum flora was observed, without obvious side effects; however, no improvement was evidenced in the findings on flow volume curve tests and arterial blood gas analysis. In advanced disease, longterm azithromycin therapy may be as effective as that with erythromycin or clarithromycin; in our view, however, its efficacy may be limited, and large-scale clinical trials are required to determine the most suitable macrolide for the treatment of CLRTIs.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Diagnosis, Differential; Drug Administration Schedule; Fatal Outcome; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections

The authors report a case of Q fever infection that caused acute exacerbation of chronic respiratory failure, which had developed as a sequela of pulmonary tuberculosis. This case was found on wide-ranging serological screening for respiratory infection performed in order to investigate the prevalence of Q fever in Japan. A 73-year-old man who had been treated for hypertension and sequelae of pulmonary tuberculosis was admitted to our hospital because of fever, productive cough, and dyspnea on effort. Hypoxia and right heart failure were detected on arterial blood analysis and ultrasonography. The acute exacerbation was triggered by respiratory infection and although the infection improved on azithromycin treatment after admission, respiratory failure continued for the period of admission. Home oxygen therapy was required for the management of chronic respiratory failure on discharge. Paired serum samples were tested for antibodies against Coxiella burnetii by indirect immunofluorescence, showing an elevated antibody titer in the convalescent phase. We believe that Q fever infection caused acute exacerbation of chronic respiratory failure, and that C. burnetii is an agent that might influence the clinical course of chronic respiratory failure.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Chronic Disease; Coxiella burnetii; Fluorescent Antibody Technique, Indirect; Humans; Male; Oxygen Inhalation Therapy; Q Fever; Respiratory Insufficiency; Serologic Tests

The antibacterial susceptibility of Chlamydia trachomatis in 138 patients with chronic prostatitis (CP) and clinical failures after antibacterial treatment with azithromycin (AZI) were investigated. Azithromycin was not found to be top-of-the-line drug in the follow-up treatment, showing only average results in vitro. The investigation of the susceptibility of chlamydia to antibiotics in causes of chronic prostatitis is highly recommended.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Humans; Male; Microbial Sensitivity Tests; Prostatitis

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Middle Aged; Suppuration

To evaluate the effectiveness of a trachoma control program in a remote community before and after major environmental health improvements.. Before-and-after cross-sectional design. The control program was in three rounds - each consisting of community census, screening of children < 13 years, health promotion activities and antibiotic treatment. There were two housing and infrastructure surveys.. Treatment of affected children and their households with azithromycin at baseline, 7 and 21 months, and health promotions. Housing and sewerage infrastructure improvements were completed at 12 months.. Large, remote Central Australian Aboriginal community, 1998-2000.. All community residents.. Prevalence of active trachoma among children under 13 years; community population changes; and adequacy of housing facilities for healthy living practices.. The prevalence of trachoma among children was 40% (95% CI, 32%-46%) at baseline, 33% (95% CI, 26%-40%) at 7 months' follow-up and 37% (95% CI, 29%-46%) at 21 months. These proportions were neither clinically nor statistically significantly different. There was a high degree of population mobility over the study period, with only 32% of residents appearing in all three censuses. The proportion of houses with completely adequate facilities increased from 0 to 16%.. Population mobility (both within and between communities), inadequate housing and continued crowding (despite improvements), as well as uncertainty about compliance with antibiotic treatment, are the likely factors contributing to the lack of effect of this trachoma control program. Because of high population mobility, a region-wide approach is needed for effective trachoma control.

Topics: Adolescent; Adult; Australia; Azithromycin; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Female; Housing; Humans; Hygiene; Infant; Male; Mass Screening; Native Hawaiian or Other Pacific Islander; Population Surveillance; Prevalence; Program Evaluation; Recurrence; Trachoma

To investigate the cause of chronic pelvic pain syndrome (CPPS) and the correlation between presence of bacterial signal and the response to antibiotics by detecting bacterial 16S rRNA gene signal using polymerase chain reaction (PCR).. EPS and first void urine (VB1) from 59 men with CPPS were analyzed by PCR for bacterial signal using universal primers specific for bacterial 16S rRNA gene. If the bacterial signal was found only in EPS or the EPS bacterial signal was at least 10 times stronger than the VB1 one, positive result could be decided for bacterial signal detection. All patients were treated with levofloxacin and azithromycin for 4 weeks. The treatment could be considered effective if more than 50% improvement, compared to the state before the treatment, was achieved in the symptom severity index(SSI), symptom frequency questionnaire(SFQ), national institutes of health chronic prostatis symptom index of pain(quasi-CPSI) or the patients' general subjective assessment.. Positive bacterial signal was detected in 46 of the 59 CPPS patients; The difference of improvement rates between positive bacterial signal group and negative bacterial signal group, which were 65%-74% and 0 respectively, was significant.. The basis of detecting 16S rRNA gene signal by PCR in clinical practice was built. The study shows that bacterial infection is related to CPPS. Bacterial signal detection results can help predict the effect of antimicrobial therapy.

Topics: Anti-Bacterial Agents; Azithromycin; Chronic Disease; Humans; Levofloxacin; Male; Ofloxacin; Pelvic Pain; Polymerase Chain Reaction; Prostatitis; RNA, Bacterial; RNA, Ribosomal, 16S

Topics: Acquired Hyperostosis Syndrome; Adult; Azithromycin; Calcitonin; Child; Chronic Disease; Diagnosis, Differential; Diphosphonates; Female; Humans; Osteomyelitis; Recurrence; Spinal Diseases

A number of studies have suggested that the non-antimicrobial actions of macrolide antibiotics may be valuable in treating patients with cystic fibrosis. The use of long-term macrolide antibiotics for the management of CF patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease was introduced into our clinic in 1997. A retrospective study was undertaken to assess of the impact of this therapy.. Twenty patients with progressive pulmonary disease (>10% fall in FEV(1) over 12 months despite optimising conventional therapy) were commenced on Azithromycin, 250 mg daily during a 21-month period. At the time of assessment they had remained on therapy for a mean of 0.9 years. Changes in lung function, weight, body mass index (BMI) and frequency of pulmonary exacerbations were assessed. A group of 20 patients with stable lung function and matched as far as possible for age and sex was identified for comparison.. Pulmonary function increased significantly in the Azithromycin group with FEV1% predicted increasing from a mean of 50.2-59.1% (P=0.001) while FVC% predicted increase from 64.5 to 76.1% (P=0.002). There was small but non-significant fall in lung function in the comparison group. Body mass index increased by a mean of 1.1 in the Azithromycin group but remained unchanged in the comparison group. The number of pulmonary exacerbations requiring intravenous antibiotics declined by 48.3% in macrolide treated subjects compared to the pre-treatment period (P<0.025); frequency of exacerbations in the control group was unchanged.. Long-term Azithromycin treatment in patients with progressive deterioration in lung function appears to have led to an improvement in pulmonary function, increased body mass index and decreased the frequency of pulmonary exacerbations requiring intravenous antibiotics.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Body Mass Index; Bronchial Diseases; Chronic Disease; Cystic Fibrosis; Disease Progression; Drug Administration Schedule; England; Female; Forced Expiratory Volume; Humans; Long-Term Care; Male; Predictive Value of Tests; Pseudomonas Infections; Recurrence; Retrospective Studies; Sputum; Treatment Outcome; Vital Capacity; Weight Gain

Topics: Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chronic Disease; Humans; Male; Prostatitis

OBJECTIVES. To determine the incidence of Ureaplasma urealyticum in women experiencing chronic urinary symptoms and to determine whether antibiotic therapy targeting these organisms is effective.. Forty-eight consecutive women referred to our academic medical center for chronic voiding symptoms and possible interstitial cystitis underwent urologic evaluation, including culture screening for U. urealyticum and Mycoplasma hominis. Patients with positive cultures were treated with a 1-g dose of azithromycin; persistent infection was treated with 7 days of doxycycline, ofloxacin, or erythromycin. Patients reported symptom severity (0, mild; 3, severe) and voiding frequency before and 6 months after treatment.. Positive cultures were obtained in 23 (48%) of 48 patients; 22 had U. urealyticum and 1 had M. hominis. All had negative cultures after treatment. The mean symptom severity score improved with treatment (2.2 to 0.7, P <0.001), and the mean urinary frequency decreased (9.2 daily to 6.8 daily, P <0.001). Two of the 23 patients experienced no improvement; one had detrusor instability and the other had medically related urinary frequency. Of the 25 patients with negative cultures, interstitial cystitis was established in only 9 (19% of the total sample).. Although often overlooked or improperly treated, U. urealyticum and M. hominis infections may account for a large proportion of unexplained chronic voiding symptoms. Culture and treatment should be considered before pursuing more costly and invasive tests.

Topics: Adolescent; Adult; Aged; Azithromycin; Bacteriological Techniques; Bacteriuria; Chronic Disease; Cystitis, Interstitial; Doxycycline; Erythromycin; Female; Humans; Middle Aged; Ofloxacin; Treatment Outcome; Ureaplasma Infections; Ureaplasma urealyticum; Urination Disorders

Borrelia burgdorferi infection in beagle dogs was studied quantitatively with skin punch biopsy samples and blood samples collected at 4- and 2-week intervals, respectively, over a 500-day period. Thereafter, 25 tissue samples of each dog were collected for further analysis. Starting at day 120 after tick challenge, 12 dogs were treated with antibiotics (azithromycin, ceftriaxone, or doxycycline) for 30 consecutive days. Four dogs received no antibiotic therapy. Quantification of B. burgdorferi DNA was done with an ABI Prism 7700 Sequence Detection System with oligonucleotide primers and a fluorescence-labeled probe designed to specifically amplify a fragment of the ospA gene of B. burgdorferi strain N40. All 16 dogs became infected with B. burgdorferi after tick challenge. In skin biopsy samples, spirochete numbers peaked at day 60 postinfection (<1.5 x 10(6) organisms per 100 microgram of extracted DNA), at the same time when clinical signs of arthritis developed in 11 of 16 dogs, and decreased to almost undetectable levels during the following 6 months. The number of B. burgdorferi organisms detected in skin biopsy samples was inversely correlated with the antibody levels measured by enzyme-linked immunosorbent assay. Antibiotic treatment reduced the amount of detectable spirochete DNA in skin tissue by a factor of 1,000 or more. At the end of the experiment, B. burgdorferi DNA was detectable at low levels (10(2) to 10(4) organisms per 100 microgram of extracted DNA) in multiple tissue samples regardless of treatment. However, more tissue samples of untreated dogs than of antibiotic-treated dogs were positive, and tissue samples of untreated dogs also were positive by culture. Only 1.6% of 576 blood samples of all dogs were positive for B. burgdorferi by PCR.

Topics: Animals; Antibodies, Bacterial; Azithromycin; Biopsy; Borrelia burgdorferi Group; Ceftriaxone; Chronic Disease; DNA, Bacterial; Dog Diseases; Dogs; Doxycycline; Lyme Disease; Microbiological Techniques; Polymerase Chain Reaction; Skin; Tissue Distribution

In this preliminary communication we report our experience with Azithromycin in patients with Chronic Recurring Multifocal Osteomyelitis (CRMO). Seven out of 13 patients, mainly teenager, showed a fast clinical improvement after they were started on Azithromycin. The immediate therapeutic effect of Azithromycin in patients with CRMO was surprising and lead us to the hypothesis that Azithromycin could have an antiphlogistic in addition to it's antibiotic effect in this disease setting. In patients with reactive chronic pelvic osteomyelitis Azithromycin obviously had a direct influence on the sympathic coxitis. Half of the patients reported an immediate reduction of pain and a significant improvement in range of movement after they were started on Azithromycin. In all cases the clinical and radiographic signs on MRI showed a reduction of the inflammatory process. Experimental animal models have recently shown that macrolids have independent additional antiinflammatory and immunomodulatory effects. The assumed local immunomodulatory effect of Azithromycin potentially is an additional activity to the already known synergistic antimicrobial and antiinflammatory effect. Right now we are in the process of collecting data from patients with SAPHO Syndrome who underwent bone-biopsies for microbiologic and histomorphologic investigations. All patients with the growth of propionibacterium acnes were started on a long-term antibiotic therapy with Azithromycin. This study will possibly help to answer the question of the additional antiphogistic/immunomodulatory effect of Azithromycin in this disease entity and the related CRMO.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Child; Chronic Disease; Female; Humans; Male; Osteomyelitis; Recurrence; Treatment Outcome

During first 3 days after patient hospitalization with pneumonia or chronic obstruction pulmonary disease (COPD) pathogens in sputum were studied according NCCLS standards (for 1999 year). Among 93 pathogens isolated in pneumonia the most frequent were S. pneumoniae (41.9%), H. influenzae (21.5%). Among 232 pathogens isolated in COPD the most frequent were S. pneumoniae (35.5%), H. influenzae (16.8%). Other pathogens were staphylococci, moraxella, gram-negative bacteria. No penicillin-resistant S. pneumoniae, were isolated, the strains with moderate penicillin resistance were less than 3% in both groups. Among H. influenzae isolated from patients with pneumonia 25% were beta-lactamase producers, from COPD patients 21% strains produced beta-lactamase. Totally among all studied pathogens only 58% were sensitive to ampicillin in pneumonia groups and 48% in COPD groups, for azithromycin 70.7% and 71% respectively, for cefuroxime 84.5% and 85% respectively. Ampicillin efficacy for empirical treatment of community-acquired low respiratory tract infections was substantially less than that of modern antibiotics.

Topics: Ampicillin; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis; Cefuroxime; Cephalosporins; Chronic Disease; Community-Acquired Infections; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Inpatients; Penicillins; Pneumonia, Bacterial; Respiratory Tract Infections; Streptococcus pneumoniae

The recognition that periodontal diseases are associated with specific pathogens has led to interest in the use of antibacterial drugs for inhibition of these microorganisms. On these bases, the present study was aimed at evaluating the tissue distribution of the new macrolide antibiotic azithromycin in patients subjected to oral surgery for chronic inflammatory diseases of both marginal and periapical periodontium.. Thirty-two patients were treated with azithromycin 500 mg/day orally for 3 consecutive days, and drug concentrations in plasma, saliva, normal gingiva, and pathological periodontal tissues were evaluated. For this purpose, samples of blood, saliva, normal gingiva, granulation tissue, and radicular granuloma or cyst wall (from dentigerous cyst) were collected during oral surgery or 0.5, 2.5, 4.5, and 6.5 days after the end of pharmacological treatment; then, azithromycin levels were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the indicator organism.. The concentrations of azithromycin in plasma, saliva, normal gingiva, and pathological tissues reached the highest values 12 hours after the last dose (0.37+/-0.05 mg/l, 2.12+/-0.30 mg/l, 6.30+/-0.68 mg/kg, and 11.60+/-1.50 mg/kg, respectively) and then declined gradually. Consistent levels of the drug in normal gingiva and pathological tissues could be detected, however, up to 6.5 days, indicating that azithromycin was retained in target tissues for a long time after the end of treatment. Moreover, azithromycin levels in both normal gingiva and pathological tissues exceeded the minimum inhibitory concentrations of most pathogens involved in the pathophysiology of chronic inflammatory periodontal diseases. Notably, azithromycin levels in pathological tissues were significantly higher than those in normal gingiva 0.5, 2.5, and 4.5 days after the last dose.. The present results indicate a marked penetration of azithromycin into both normal and pathological periodontal tissues, suggesting that azithromycin represents a promising option in both adjunctive and prophylactic treatments of chronic inflammatory periodontal diseases.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Chronic Disease; Dentigerous Cyst; Female; Follow-Up Studies; Gingiva; Granulation Tissue; Humans; Male; Microbial Sensitivity Tests; Micrococcus; Middle Aged; Periapical Granuloma; Periapical Periodontitis; Periapical Tissue; Periodontitis; Periodontium; Saliva; Tissue Distribution

The purpose of the present study was to evaluate the combination of azithromycin and rifampicin on experimental chronic osteomyelitis due to Staphylococcus aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor (TNF), a cytokine implicated in inflammation-induced bone pathology, and histopathological changes during infection and following antibiotic treatment were evaluated. Rats were infected with S. aureus by direct tibial inoculation and then randomized 56 days after infection to receive saline treatment or a combination of azithromycin and rifampicin (50 mg/kg po and 25 mg/kg sc respectively) once daily for 21 days. The combination of azithromycin and rifampicin was successful as determined by dramatic reduction in bone bacterial counts (approximately log 4 cfu), but regrowth of the organisms occurred suggesting that the duration of treatment was insufficient. TNF alpha mRNA and TNF activity were constantly elevated by approximately 20- and >200-fold, respectively, and remained elevated irrespective of antimicrobial treatment. Bone histology revealed extensive increase in bone turnover in both the infected and antibiotic treated bones with no difference being observed between the groups. This suggests that, in infected bone, the elevated TNF levels observed may be directly related to the bone pathology and both remain largely unchanged despite potent antibiotic therapy.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Bone and Bones; Chronic Disease; Disease Models, Animal; Drug Therapy, Combination; Osteomyelitis; Rats; Rifampin; RNA, Messenger; Staphylococcus aureus; Tumor Necrosis Factor-alpha

Babesiosis is a malaria-like, tick-transmitted zoonosis caused by protozoa of the family Piroplasmorida, which includes Babesia and Theileria species. In the United States, the infection is endemic in the Northeast and upper Midwest, although cases have recently been described in Northern California and Washington State. We report a case of babesiosis in a patient infected with HIV who presented with a prolonged fever of unknown origin; the patient had not undergone splenectomy. Parasitemia persisted despite initial clinical improvement after treatment with quinine and clindamycin. Babesiosis was controlled with a maintenance regimen consisting of clindamycin, doxycycline, and high-dose azithromycin, but the infection was not eradicated. Babesiosis should be considered in the differential diagnosis of HIV-infected patients with fevers and/or anemia in areas where the infection is endemic. HIV-infected patients who are severely immunosuppressed, even those without a history of splenectomy, may present with severe manifestations of babesiosis and develop a chronic infection, which may require therapy to prevent relapse of disease.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; Azithromycin; Babesiosis; Chronic Disease; Clindamycin; Doxycycline; Drug Therapy, Combination; Fever of Unknown Origin; Humans; Male; Parasitemia; Quinine

The activities of therapeutic regimens with azithromycin (AZI) and doxycycline combined with streptomycin (DOX-SM) were compared in Brucella melitensis infected mice. In a chronic model, AZI given over 10, 14 or 21 consecutive days (50 mg/kg/24 h) significantly reduced the infection (1.3-1.6 logs, day 48 post-infection). However, the effectiveness of DOX (21 days, 50 mg/kg/12 h) was higher than AZI (3.4 logs of reduction, day 48 post-infection). Besides, when DOX was administered for 45 days, it "cured" all the animals from day 78. Similar results were obtained in an acute model infection. One single dose of DOX or DOX-SM, starting one day after lethal challenge, was able to protect 83% of the mice. In contrast, only 25% of the mice treated with AZI (50-200 mg/Kg) survived the challenge. Our findings demonstrate that AZI, in contrast to DOX-SM, does not cure experimental brucellosis.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Azithromycin; Brucella melitensis; Brucellosis; Chronic Disease; Colony Count, Microbial; Doxycycline; Drug Combinations; Female; Mice; Spleen; Streptomycin

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Bronchitis; Chronic Disease; Drug Evaluation; Female; Humans; Male; Middle Aged; Risk Factors; Superinfection

We compared the activities of azithromycin, erythromycin, and penicillin G in a mouse model of systemic infection and septic arthritis induced by type IV group B streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were analyzed relative to the pharmacokinetics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal drug administration was initiated with different dose regimens at different times after infection. A single dose of azithromycin (100 mg/kg) strongly reduced the incidence of articular lesions with respect to that with erythromycin or penicillin G. Treatment with azithromycin (three intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculated 30 min after infection and at high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin was much more active than erythromycin and penicillin G with respect to bacterial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was employed. The pharmacokinetics of azithromycin account for its superior in vivo efficacy against type IV GBS. A longer half-life and higher levels of this drug in serum and tissues with respect to those for erythromycin or penicillin G were achieved. The high affinity of azithromycin for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestation of GBS infection.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Azithromycin; Chronic Disease; Erythromycin; Female; Joints; Kidney; Male; Mice; Microbial Sensitivity Tests; Penicillin G; Penicillins; Streptococcal Infections; Streptococcus agalactiae

The activities of a short therapeutic regimen with azithromycin and the classic treatment doxycycline with streptomycin were compared and evaluated in mice infected with Brucella melitensis. In a chronic model, starting therapy 31 days after challenge, azithromycin (10 days, 50 mg/kg/day) significantly reduced the infection (2.9 logs, day 48 post-infection). The effectiveness of doxycycline (21 days, 50 mg/kg/12 hourly) was greater than azithromycin (4.1 logs of reduction, day 48 post-infection), and when doxycycline was administered for a period of 45 days, all the animals were bacteriologically cured from day 78. The combination with streptomycin (14 days, 10 mg/kg/day) did not improve the effect of any of the regimens. In an acute model infection, treatments with doxycycline or doxycycline-streptomycin, for a period of 3 days, starting 1 day after lethal challenge, were able to protect all the mice. In contrast, only 50% of the mice treated with azithromycin survived the challenge. In conclusion, although a short oral treatment with azithromycin was able to reduce the infection significantly, it was not able to cure the animals as effectively as the classic regimen with doxycycline administered for a longer period of time.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Azithromycin; Brucella abortus; Brucella melitensis; Brucellosis; Chronic Disease; Doxycycline; Drug Therapy, Combination; Female; Mice; Mice, Inbred BALB C; Organ Size; Spleen; Streptomycin

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Topics: Animals; Azithromycin; Brain; Chronic Disease; Disease Models, Animal; Drug Administration Schedule; Drug Evaluation, Preclinical; Mice; Mice, Inbred C57BL; Toxoplasma; Toxoplasmosis, Animal

We report the case of an apparently immunocompetent woman whose symptoms and signs have persisted for 8 years following a serologically and histologically confirmed diagnosis of toxoplasmosis. During this period she had two successful pregnancies despite persistently increased anti-toxoplasma IgM antibodies. Neither child is infected.

Topics: Adult; Azithromycin; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunocompetence; Immunoglobulin M; Lymphatic Diseases; Pyrimethamine; Sulfadiazine; Toxoplasmosis

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 micrograms/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 micrograms/g, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 micrograms/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.

Topics: Administration, Oral; Adult; Azithromycin; Capsules; Chronic Disease; Drug Administration Schedule; Erythromycin; Half-Life; Humans; Male; Palatine Tonsil; Time Factors; Tonsillitis

The concentrations of azithromycin in sinus fluid and mucosal tissue were determined in a total of 23 patients with acute or chronic sinusitis. Five patients with acute sinusitis and four with chronic sinusitis were administered a five-day course of oral azithromycin (500 mg on day 1, 250 mg on days 2-5, all as single doses), and the remaining 14 patients, all with chronic sinusitis, received single oral doses of azithromycin (500 mg). With the five-day regimen, the mean levels of azithromycin in sinus fluid were markedly higher in patients with acute sinusitis (1.34 micrograms/ml) than in patients with chronic sinusitis (0.25 micrograms/ml) 24 h after the first dose. The levels of azithromycin in the sinus fluid increased from the first to the last dose in both patient groups; the mean levels of azithromycin 24 h after the last dose were 2.33 micrograms/ml in acute sinusitis patients and 0.38 micrograms/ml in chronic sinusitis patients. In chronic sufferers, the mean levels of azithromycin in the sinus fluid following a single oral dose were 0.25, 0.41, 0.57 and 0.22 micrograms/ml at 24, 48, 72 and 96 h, respectively, after administration. In these patients the mean sinus drug concentrations were much greater in the mucosal tissue (1.23 micrograms/g) than in the sinus fluid (0.41 micrograms/ml) 48 h after administration of the single dose. There were no treatment-related changes in laboratory function tests, and side effects were described as mild to moderate (five patients complained of nausea, abdominal pain or headache).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Administration, Oral; Adult; Aged; Azithromycin; Body Fluids; Chronic Disease; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Maxillary Sinusitis; Middle Aged; Nasal Mucosa