Azithromycin is prescribed to treat various bacterial respiratory and skin infections.

Lung Delivery of Lactose-Free Microparticles Loaded with Azithromycin for the Treatment of Bacterial Infections. 2025. https://doi.org/10.3390/pharmaceutics17060770

Background/Objectives: Respiratory bacterial infections remain a significant global health challenge, with effective drug delivery to the lungs being crucial for successful treatment. This study aimed to develop a lactose-free dry powder inhaler (DPI) formulation containing azithromycin (AZM) microparticles for enhanced pulmonary delivery. Methods: Using a quality-by-design approach, an optimized formulation (4% AZM, 20% leucine, and 76% mannitol) was achieved. Results: The formulation demonstrated excellent aerodynamic properties with a mass median aerodynamic diameter (MMAD) of 2.72 μm ± 0.01 μm and fine particle fraction (FPF) (<5 μm) of 65.42% ± 5.12%. AZM-loaded microparticles exhibited enhanced efficacy against Pseudomonas aeruginosa with a two-fold reduction in the minimum bactericidal concentration (7.81 μg/mL vs. 15.62 μg/mL) compared to unprocessed AZM, while maintaining activity against Streptococcus pneumoniae. AZM microparticles demonstrated good biocompatibility with red blood cells and bronchial epithelial cells at therapeutic concentrations. Conclusions: These findings establish a promising lactose-free antibiotic formulation for targeted pulmonary delivery with enhanced antimicrobial efficacy.

Empiric Azithromycin in COVID-19 Impacts the Respiratory Microbiome and Antimicrobial Resistome without Anti-inflammatory Benefit. 2025. https://doi.org/10.21203/rs.3.rs-6875205/v1

Azithromycin is often prescribed unnecessarily for respiratory infections, many of which are viral. During the COVID-19 pandemic, its use was widespread, in part due to alleged therapeutic benefits, which have since been disproven. Here, we sought to understand the impact of azithromycin exposure on the respiratory microbiome, antimicrobial resistome, and host immune response in a prospective multicenter cohort of 1164 patients hospitalized for SARS-CoV-2 infection. Using longitudinal nasal metatranscriptomics, we compared patients treated with azithromycin (n=366, 31.4%) to those who received no antibiotics (n=474, 40.7%) or antibiotics other than azithromycin (n=324, 27.8%). We found that azithromycin treatment altered the community composition of the nasal microbiome, reducing bacterial relative abundance, increasing fungal relative abundance, and increasing potentially pathogenic taxa such as Klebsiellaand Staphylococcus. Azithromycin treatment was most notably associated with increases in the number of detectably expressed macrolide/lincosamide/streptogramin (MLS) antimicrobial resistance genes, as well as their relative proportion in the resistome, with changes observable after one day of exposure. Of the MLS resistance genes, the expression of ermC, msrA and ermX increased the most in patients receiving azithromycin. Correlation analyses demonstrated that MLS resistance gene expression was significantly associated with the abundance of several taxa, including both commensal (e.g., Dolosigranulum, Corynebacterium) and potentially pathogenic genera (e.g., Streptococcus, Staphylococcus). Assessment of the peripheral blood and upper airway host transcriptome demonstrated no differences in the expression of inflammatory genes. Taken together, our findings demonstrate that azithromycin treatment in COVID-19 leads to dysbiosis of the upper respiratory microbiome and changes in the expression of MLS resistance genes, without apparent anti-inflammatory benefit.

Azithromycin-loaded liposomes and niosomes for the treatment of skin infections: Influence of excipients and preparative methods on the functional properties.. 2024. https://doi.org/10.1016/j.ejpb.2024.114233

The aim of this study was to develop azithromycin (AZT)-loaded liposomes (LP) and niosomes (NS) useful for the treatment of bacterial skin infections and acne. LP based on phosphatidylcholine from egg yolk (EPC) or from soybean lecithin (SPC), and NS composed of sorbitan monopalmitate (Span 40) or sorbitan monostearate (Span 60) were prepared through the thin film hydration (TFH) and the ethanol injection (EI) methods. The formulations were subsequently characterized for their physico-chemical and functional properties. Vesicles prepared through TFH showed higher average sizes than the corresponding formulations obtained by EI. All the vesicles presented adequate encapsulation efficiency and a negative ζ potential, which assured good stability during the storage period (except for LP-SPC). Formulations prepared with TFH showed a more prolonged AZT release than those prepared through EI, due to their lower surface area and multilamellar structure, as confirmed by atomic force microscopy nanomechanical characterization. Finally, among all the formulations, NS-Span 40-TFH and LP-EPC-TFH allowed the highest drug accumulation in the skin, retained the antimicrobial activity and did not alter fibroblast metabolism and viability. Overall, they could ensure to minimize the dosing and the administration frequency, thus representing promising candidates for the treatment of bacterial skin infections and acne.

Inhaleddry powder liposomal azithromycin for treatment of chronic lower respiratory tract infection.. 2024. https://doi.org/10.1016/j.ijpharm.2024.123841

A dry powder inhaled liposomal azithromycin formulation was developed for the treatment of chronic respiratory diseases such as cystic fibrosis and bronchiectasis. Key properties including liposome size, charge and encapsulation efficiency powder size, shape, glass transition temperature (Tg), water content and in vitro respiratory deposition were determined. Antimicrobial activity against cystic fibrosis (CF) respiratory pathogens was determined by MIC, MBC and biofilm assays. Cytotoxicity and cellular uptake studies were performed using A549 cells. The average liposome size was 105 nm, charge was 55 mV and encapsulation efficiency was 75%. The mean powder particle size d[v,50] of 4.54 µm and Mass Median Aerodynamic Diameter (MMAD) was 5.23 µm with a mean Tg of 76˚C and water content of 2.1%. These excellent physicochemical characteristics were maintained over one year. Liposomal loaded azithromycin demonstrated enhanced activity against P. aeruginosa clinical isolates grown in biofilm. The formulation was rapidly delivered into bacterial cells with >75% uptake in 1 hour. Rapid uptake into A549 cells via a cholesterol-dependent endocytosis pathway with no cytotoxic effects apparent. These data demonstrate that this formulation could offer benefits over current treatment regimens for people with chronic respiratory infection.

Azithromycin. https://en.wikipedia.org/wiki/Azithromycin

several bacterial infections. These include middle ear infections, strep throat, pneumonia, traveler's diarrhea, sexually transmitted infection, and certain Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used to treat several bacterial infections. These include middle ear infections, strep throat, pneumonia, traveler's diarrhea, sexually transmitted infection, and certain other intestinal infections. Along with other medications, it may also be used for malaria. It is adminis Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used to treat several bacterial infections. These include middle ear infections, strep throat, pneumonia, traveler's diarrhea, sexually transmitted infection, and certain other intestinal infections. Along with other medications, it may also be used for malaria. It is administered by mouth, into a vein, or as topical treatment for the eye. Common side effects include nausea, vomiting, diarrhea and upset stomach. An allergic reaction, such as anaphylaxis, or a type of diarrhea caused by Clostridioides difficile is possible. Azithromycin causes QT prolongation that may cause life-threatening arrhythmias such as torsades de pointes. While some studies claim that no harm has been found with use during pregnancy, more recent studies with mice during late pregnancy has shown adverse effects on embryonic testicular and neural development of prenatal azithromycin exposure (PAzE). However, there need to be more well-controlled studies in pregnant women. Its… A…