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

<b>Background/Objectives:</b> 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 <i>methicillin-resistant Staphylococcus aureus</i> (<i>MRSA</i>) and <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>). <b>Methods:</b> A total of 87 sputum samples (n = 87) were collected and analyzed. The <i>ermB</i> gene for <i>K. pneumoniae</i> and the <i>ermA</i> gene for <i>MRSA</i> were used to confirm resistant isolates. Among 87 samples, 29 manifested <i>K. pneumoniae</i>, 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. <b>Results:</b> The results elucidate resistance of <i>K. pneumoniae</i> against several antibiotics, including azithromycin (15 µg), chloramphenicol (30 µg), and amoxicillin (30 µg), while <i>MRSA</i> 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. <b>Conclusions:</b> Notably, a strong synergistic effect was observed with AZM-CSNPs in combination with cetirizine, significantly enhancing antibacterial efficacy against resistant isolates.