zithromax and Tuberculosis

Bronchiolitis obliterans syndrome (BOS) is one of the main causes of mortality after lung and bone marrow transplantation. Up to 75% of lung transplantation patients develop BOS within 5 years, whereas after bone marrow transplantation 14% of the patients develop the disease with 65% mortality within 3 years. Patients demonstrate gradual decrease in pulmonary functions with no significant anatomic/imagine findings. Therapeutic trials with high dose systemic corticosteroids, immune suppression and immunomodulation did not show any significant success. However, macrolides and especially azithromycin have recently been reported as highly efficient for BOS. This review summarizes information on the disease focusing on the clinical experience with azithromycin as a treatment for BOS.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Bronchiolitis Obliterans; Humans; Tuberculin Test; Tuberculosis

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

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

Mycobacterium avium infection is a frequent complication during the late stage of AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are bactericidal against M. avium, and their use has dramatically improved the prognosis of this infection. In vitro, azithromycin has MICs against M. avium ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low concentrations in serum, close to 0.4 mg/l, very high intracellular concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is active in vitro in the model of macrophage infection. Furthermore, azithromycin is active against murine experimental infection with M. avium. Clinical studies conducted among patients with AIDS have shown that azithromycin was active against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies are designed to better determine the ideal dose, to compare its activity with that of clarithromycin and to determine the antibiotics that could be combined to prevent the selection of resistant mutants. Other ongoing studies are evaluating the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Humans; In Vitro Techniques; Macrophages; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rats; Tuberculosis

Clinical practice and diagnostic algorithms often assume that tuberculosis can be ruled out in mycobacteriology-negative individuals whose symptoms improve with a trial-of-antibiotics. We aimed to investigate diagnostic performance, clinical benefit, and antimicrobial resistance using a randomised controlled trial.. In this three-arm, individually randomised, open-label, controlled trial, we enrolled Malawian adults (aged ≥18 years) attending primary care who reported being unwell for at least 14 days (including cough) with no immediate indication for hospitalisation at Limbe and Ndirande Health Centres in Blantyre. Participants were randomly allocated (1:1:1) to azithromycin (500 mg taken once per day for 3 days), amoxicillin (1 g taken three times per day for 5 days), or standard of care with no immediate antibiotics, stratified by study site. Sputum at enrolment and day 8 was tested for tuberculosis (microscopy, Xpert MTB/RIF, and culture). The primary efficacy outcome was day 8 specificity (percentage with symptom improvement among mycobacteriology-negative participants), and day 29 clinical outcome (death, hospitalisation, or missed tuberculosis diagnosis) among all randomised participants. This study is registered with ClinicalTrials.gov, NCT03545373.. Between Feb 25, 2019, and March 14, 2020, 5825 adults were screened and 1583 (mean age 36 years; 236 [14·9%] HIV positive) were randomly assigned to standard of care (530 participants), azithromycin (527 participants), or amoxicillin (526 participants) groups. Overall, 6·3% (100 of 1583 participants) had positive baseline sputum mycobacteriology. 310 (79·1%) of 392 patients receiving standard of care reported symptom improvement at day 8, compared with 340 (88·7%) of 383 patients receiving azithromycin (adjusted difference 8·6%, 95% CI 3·9-13·3%; p<0·0004) and 346 (89·4%) of 387 receiving amoxicillin (adjusted difference 8·8%, 4·0-13·6%; p=0·0003). The proportion of participants with day 29 composite clinical outcomes was similar between groups (standard of care 1% [7 of 530 participants], azithromycin 1% [6 of 527 participants], amoxicillin 2% [12 of 526 participants]).. Routine outpatient trial-of-antibiotics during tuberculosis investigations modestly improved diagnostic specificity for mycobacteriologically confirmed tuberculosis but had no appreciable effect on death, hospitalisation, and missed tuberculosis diagnosis. These results confirm the limited benefit of trial-of-antibiotics, presenting an opportunity for discontinuation of trial-of-antibiotics and improved antimicrobial stewardship during tuberculosis screening, without affecting clinical outcomes.. Northern Norway Regional Health Authority (Helse Nord RHF), Commonwealth Scholarship Commission in the UK, Wellcome Trust, UK Medical Research Council, and the UK Department for International Development.

Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Humans; Malawi; Mycobacterium tuberculosis; Tuberculosis

In pandemic conditions, situation of active and uncontrolled use by population of antimicrobial preparations treating COVID-19 occurs. So, new risks of development of medication resistance among patients with various infectious diseases, tuberculosis included, appear. The purpose of the study is to characterize prevalence of antimicrobial preparations use by population in relationship with development of medication resistance in patients with tuberculosis during COVID-19 pandemic. Material and methods. The analysis of sales of antimicrobial medicines was implemented on the basis of published official data from the joint-stock company DSM Group presenting monthly audit of the Russian pharmaceutical market. The determination of primary antibiotic resistance was carried out in 2018-2020 on 3312 patients with tuberculosis. The modified method of proportions on liquid nutrient medium in system with automated accounting of microorganisms growth, the method of absolute concentrations and the method of polymerase chain reaction with real-time detection were applied. The results of the study. It was established that the most demanding antimicrobial medications among population were ceftriaxone, azithromycin, levofloxacin, moxifloxacin, azithromycin. At the same time, the maximum increase in sales in 2020 up to 150% as compared with of 2019 was determined in medications derived from quinolone moxifloxacin, levofloxacin, which began to be used in treatment of coronavirus infection. At the same time, these medications are traditionally used in tuberculosis treatment. But in 2020, alarming trend was established that limits treatment of tuberculosis patients. The primary resistance of mycobacteria was also established in newly diagnosed tuberculosis patients, also for the same antimicrobial medications of quinolone derivatives, and increasing in proportion of patients with primary medication resistance to levofloxacin, moxifloxacin in 2020 as compared to 2018 was 189-480%. At the same time, increasing of resistance to other antibiotics made up to 60.8% on average. Conclusion. The study results imply alarming scenario of medication resistance shifts towards very virulent and highly medication-resistant genotypes. This trend can result in conditions of successful transmission of deadly medication-resistant mutants that can seriously undermine effectiveness of implemented programs of struggle with tuberculosis worldwide.

Topics: Anti-Infective Agents; Antitubercular Agents; Azithromycin; COVID-19; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Levofloxacin; Moxifloxacin; Mycobacterium tuberculosis; Pandemics; Quinolones; Tuberculosis

Topics: Adult; Aged; Antitubercular Agents; Antiviral Agents; Azithromycin; Betacoronavirus; Clinical Laboratory Techniques; Cohort Studies; Coinfection; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Drug Combinations; Emigrants and Immigrants; Female; Humans; Hydroxychloroquine; Lopinavir; Lung; Male; Middle Aged; Mortality; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Tomography, X-Ray Computed; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Desensitization, Immunologic; Dose-Response Relationship, Immunologic; Drug Hypersensitivity; Female; Humans; Mycobacterium avium; Treatment Outcome; Tuberculosis

The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection.

Topics: Animals; Azithromycin; Clarithromycin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mycobacterium avium; Rifampin; Tuberculosis

The comparative activities of azithromycin and clarithromycin and the activities of azithromycin alone and in combination with other antimycobacterial agents were evaluated in the beige mouse model of disseminated Mycobacterium avium complex infection. Azithromycin was similar in activity to clarithromycin. Azithromycin plus clofazimine plus ethambutol reduced the number of splenic organisms more than azithromycin alone, while the combination was less active than azithromycin alone for bacteria in lungs. Rifabutin had activity similar to that of azithromycin for organisms in spleens and lungs. Rifabutin plus azithromycin was more active than either agent alone for organisms in spleens, but the combination's activity was not significantly different from that of rifabutin for organisms in lungs. The activity of azithromycin against several M. avium complex isolates was evaluated. The reduction of viable cell counts in spleens ranged from 1.7 to 0.8 log units. For the three isolates studied, there was little correlation between the in vitro MIC and the in vivo activity.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Culture Media; Drug Therapy, Combination; Erythromycin; Female; Male; Mice; Mice, Inbred C57BL; Mycobacterium avium; Tuberculosis