Macrolides as dual-action agents: antibacterial and immunomodulatory effects in respiratory diseases

Ahmad Zul Helmy Bin Abd Razak; Muhammad Adam Wajdi Bin Yahya; Muhammad Ammar Haziq Bin Mohamad Sobri; Muhammad Syazwan Bin Mohamad Zamri

Authors

Ahmad Zul Helmy Bin Abd Razak Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia
Muhammad Adam Wajdi Bin Yahya Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia
Muhammad Ammar Haziq Bin Mohamad Sobri Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia
Muhammad Syazwan Bin Mohamad Zamri Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia

Keywords:

Macrolides, Azithromycin, Antibacterial, Immunomodulation, Respiratory diseases, Antimicrobial resistance

Abstract

This review explores the dual role of macrolide antibiotics, focusing on their antibacterial spectrum and immunomodulatory effects, particularly in the treatment of respiratory diseases. A narrative review of the literature was performed using PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar, covering English-language experimental studies, clinical trials, meta-analyses and clinical guidelines published until 2024. Macrolides, such as azithromycin, clarithromycin, and erythromycin, inhibit bacterial protein synthesis and are effective against common respiratory pathogens, including atypical organisms like Mycoplasma pneumoniae. The pharmacokinetics, especially azithromycin’s high lung tissue concentration, support their use in conditions like community-acquired pneumonia. In addition to their antimicrobial action, macrolides exhibit significant immunomodulatory effects by reducing inflammatory cytokines, neutrophil activity, and mucus production, which is beneficial in chronic respiratory diseases such as COPD, bronchiectasis, asthma, and cystic fibrosis. Clinical studies have demonstrated that long-term macrolide therapy can decrease the frequency of exacerbations and improve quality of life in selected patients. However, concerns over antimicrobial resistance and potential side effects, including gastrointestinal issues and QT prolongation, necessitate careful patient selection and monitoring. The findings emphasize the importance of tailoring macrolide use based on local resistance patterns, disease characteristics, and individual patient profiles. This review highlights macrolides as valuable agents with both antibacterial and anti-inflammatory properties, supporting their strategic use in respiratory disease management.

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