# Synergistic Antibacterial Activity of Azithromycin-Loaded Chitosan Nanoparticles Alone and in Combination with Cetirizine Dihydrochloride Against Resistant Isolates of Respiratory Tract Infections

## TL;DR

This study explores how combining azithromycin-loaded chitosan nanoparticles with cetirizine improves antibacterial effects against drug-resistant respiratory infections.

## Contribution

The novel contribution is demonstrating a synergistic effect of azithromycin-loaded nanoparticles with cetirizine against resistant bacterial isolates.

## Key findings

- Azithromycin-loaded chitosan nanoparticles reduced the minimum inhibitory concentration against resistant isolates.
- Combining the nanoparticles with cetirizine down-regulated resistance genes in MRSA and Klebsiella pneumoniae.
- The combination therapy showed a strong synergistic antibacterial effect against drug-resistant respiratory bacteria.

## Abstract

Background/Objectives: Antibiotic resistance is a major public health concern, with considerable socio-economic consequences. Researchers are exploring alternative strategies, including nanotechnology, which has shown significance in targeted drug delivery. This study evaluates the synergistic antibacterial activity of azithromycin-loaded chitosan nanoparticles (AZM-CSNPs) against azithromycin-resistant clinical respiratory isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae (K. pneumoniae). Methods: A total of 87 sputum samples (n = 87) were collected and analyzed. The ermB gene for K. pneumoniae and the ermA gene for MRSA were used to confirm resistant isolates. Among 87 samples, 29 manifested K. pneumoniae, and 32 exhibited MRSA-positive cultures, confirmed through phenotypic and genotypic methods. The RT-PCR is performed by using a cDNA Kit to determine the gene expression. Results: The results elucidate resistance of K. pneumoniae against several antibiotics, including azithromycin (15 µg), chloramphenicol (30 µg), and amoxicillin (30 µg), while MRSA also showed resistance to cefoxitin (30 µg), azithromycin (15 µg), and gentamycin (10 µg). Reduction in the MIC value of the nanoparticle formulation showed their effectiveness. The AZM-CSNPs combined with cetirizine dihydrochloride helped to down-regulate the resistant genes. Conclusions: Notably, a strong synergistic effect was observed with AZM-CSNPs in combination with cetirizine, significantly enhancing antibacterial efficacy against resistant isolates.