Tags

Type your tag names separated by a space and hit enter

Azithromycin: mechanisms of action and their relevance for clinical applications.
Pharmacol Ther. 2014 Aug; 143(2):225-45.P&T

Abstract

Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk.

Authors+Show Affiliations

Fraunhofer Institute for Molecular Biology and Applied Ecology, Project Group Translational Medicine and Pharmacology, Frankfurt am Main, Germany; Institute of Pharmacology for Life Scientists, Goethe University Frankfurt, Frankfurt am Main, Germany; Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt am Main, Germany. Electronic address: michael.parnham@ime.fraunhofer.de.Fidelta d.o.o., Zagreb, Croatia. Electronic address: Vesna.ErakovicHaber@glpg.com.4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany. Electronic address: egiamarel@med.uoa.gr.Biomedical Research Division, Department of Theoretical and Applied Sciences, University of Insubria, Busto A., Varese, Italy; Department of Basic Medical Sciences, Ghent University, Ghent, Belgium. Electronic address: gianpaolo.perletti@uninsubria.it.Respiratory Division, Lung Transplantation Unit, University Hospitals Leuven and Department of Clinical and Experimental Medicine, KU Leuven, Belgium. Electronic address: geert.verleden@uzleuven.be.Respiratory Division, Lung Transplantation Unit, University Hospitals Leuven and Department of Clinical and Experimental Medicine, KU Leuven, Belgium. Electronic address: robin.vos@uzleuven.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24631273

Citation

Parnham, Michael J., et al. "Azithromycin: Mechanisms of Action and Their Relevance for Clinical Applications." Pharmacology & Therapeutics, vol. 143, no. 2, 2014, pp. 225-45.
Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, et al. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143(2):225-45.
Parnham, M. J., Erakovic Haber, V., Giamarellos-Bourboulis, E. J., Perletti, G., Verleden, G. M., & Vos, R. (2014). Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacology & Therapeutics, 143(2), 225-45. https://doi.org/10.1016/j.pharmthera.2014.03.003
Parnham MJ, et al. Azithromycin: Mechanisms of Action and Their Relevance for Clinical Applications. Pharmacol Ther. 2014;143(2):225-45. PubMed PMID: 24631273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Azithromycin: mechanisms of action and their relevance for clinical applications. AU - Parnham,Michael J, AU - Erakovic Haber,Vesna, AU - Giamarellos-Bourboulis,Evangelos J, AU - Perletti,Gianpaolo, AU - Verleden,Geert M, AU - Vos,Robin, Y1 - 2014/03/11/ PY - 2014/03/04/received PY - 2014/03/04/accepted PY - 2014/3/18/entrez PY - 2014/3/19/pubmed PY - 2015/2/24/medline KW - Azithromycin KW - Clinical efficacy KW - Immunomodulation KW - Macrolide antibiotic KW - Mechanisms of action KW - Pharmacokinetics SP - 225 EP - 45 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 143 IS - 2 N2 - Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/24631273/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(14)00055-2 DB - PRIME DP - Unbound Medicine ER -