azithromycin

azithromycin

Overview

Azithromycin is a macrolide antibiotic used in the treatment of a range of bacterial infections. It acts by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit, thereby suppressing bacterial growth. Clinically, it is valued for its broad antibacterial activity, convenient dosing, and tissue penetration, and it is also studied in formulations designed to improve local delivery and antimicrobial performance.

Beyond its established role as an anti-infective agent, azithromycin continues to be investigated in contexts involving respiratory infection, biofilm-associated disease, and drug resistance. Recent research has also examined its use alongside other therapies such as menadione, doxycycline, cefdinir, and intravenous immunoglobin, as well as in settings where cardiac safety concerns such as QT interval prolongation and comorbid conditions like arterial hypertension, heart failure, and obesity may be relevant to treatment decisions.

Focus of Latest Publications

Recent publications on azithromycin have focused on both clinical use and formulation-based strategies. In pediatric Mycoplasma pneumoniae pneumonia, a multicentre randomized trial protocol is comparing doxycycline with azithromycin as first-line therapy for children with suspected macrolide-resistant infection, reflecting ongoing concern about treatment failure in regions where macrolide-resistant M. pneumoniae is increasing. In parallel, a historical cohort study in COVID-19 patients examined QT interval changes during lopinavir-ritonavir treatment with or without azithromycin and/or hydroxychloroquine; the study reported an overall increase in mean corrected QT interval after treatment, but QTc prolongation was observed only in patients receiving lopinavir-ritonavir monotherapy who also had cardiovascular conditions, angina pectoris, or hypomagnesemia, while those receiving concomitant azithromycin or hydroxychloroquine did not show this effect.

Other recent work has explored azithromycin resistance and drug-interaction safety. In Rickettsia typhi, investigators sought to induce azithromycin resistance and identify its genetic basis, reporting that a repetitive nucleotide insertion in the rplV gene was associated with in vitro resistance, in the context of murine typhus treatment failure reports from Laos. Separately, a population-based study of opioid toxicity found increased risk with CYP3A4-inhibiting macrolides, but observed no association with azithromycin, consistent with its lack of CYP3A4 inhibition.

Azithromycin has also been incorporated into novel delivery systems aimed at improving local efficacy. One study developed nano-in-micro dry powder inhalable formulations combining azithromycin with menadione for pulmonary Pseudomonas aeruginosa biofilms. The nano-embedded microparticles showed favorable aerodynamic properties for bronchial delivery, enhanced antibiofilm activity compared with the microparticle matrix-only formulation, and preserved epithelial safety in Calu-3 cells under nebulized and dry powder exposure conditions. Another study created azithromycin-loaded chitosan films for oral tissue regeneration, showing sustained zero-order release, tunable mechanical properties, antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae, and maintained viability of fibroblasts and osteoblasts at clinically relevant extract levels, alongside hydration-triggered conformability and adhesion in ex vivo models.

Overall, these publications highlight azithromycin as a comparator in pediatric pneumonia, a co-exposure in cardiac safety analyses, a target for resistance investigation, and a component of advanced local delivery platforms. The studies collectively emphasize its continuing relevance in infectious disease treatment, formulation science, and safety evaluation.

Key Publications

  • May Efficacy and safety of Doxycycline versus Macrolides for Mycoplasma pneumoniae INfectiOn in Children (DOMINO): a protocol for a multicentre, randomised, open-label, superiority trial. (BMJ open, 2026, PMID 42191206): "This study aims to evaluate the efficacy and safety of doxycycline compared with azithromycin as a first-line treatment for children with pneumonia suspected of MRMP infection."
  • Jun Nano-in-micro dry powder formulations combining azithromycin and menadione as adjuvant against pulmonary P. aeruginosa infections. (International journal of pharmaceutics, 2026, PMID 42097470): "This study explores a nano-in-micro inhalable formulation design that combines azithromycin (AZM) with the antibiotic adjuvant menadione (MEN) to enhance antibiofilm activity under biorelevant pulmonary exposure conditions."
  • Jun QT interval prolongation and its related factors before and after receiving lopinavir-ritonavir in the COVID-19 era: a historical cohort study. (Virus research, 2026, PMID 42067143): "...with or without azithromycin and/or hydroxychloroquine..."
  • Apr A repetitive nucleotide insertion in the rplV gene is associated with in vitro resistance to azithromycin in Rickettsia typhi. (PLoS neglected tropical diseases, 2026, PMID 42044123): "where azithromycin treatment failure has been reported."
  • Apr Opioid Toxicity Following Concomitant Use of Macrolide Antibiotics with Fentanyl, Hydromorphone, or Oxycodone: A Population-Based Study. (Clinical pharmacology and therapeutics, 2026, PMID 41944476): "We observed no associations with azithromycin, a non-CYP3A4 inhibiting macrolide."
  • Apr Azithromycin-loaded chitosan films: a multifunctional platform for oral tissue regeneration. (International journal of pharmaceutics, 2026, PMID 41833846): "All films ensured zero-order azithromycin release (R2 = 0.96-0.98) with anomalous diffusion contribution (Peppas n = 0.41-0.46)."