As is known, ezetimibe is the only drug classified as a cholesterol absorption inhibitor, working by preventing the cholesterol transporter protein Niemann-Pick C1-Like 1 (NPC1L1) from functioning. This compound is a derivative of Azetidinone and substituted β-lactam. However, its antibacterial activity has not yet been fully established.

We also evaluated the antibacterial activity of ezetimibe using the agar-well diffusion method against multiple bacterial strains, including both gram-negative and gram-positive bacteria. Subsequently, we determined the minimum inhibitory concentration (MIC) values for ezetimibe on sensitive strains. Oxacillin and amoxicillin were used as controls for comparison.

The results confirmed that ezetimibe bound to the target receptor, and its binding energy (-138.018 kcal/mol) was higher than that of most β-lactam antibiotics. Ezetimibe did not show any activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, or Proteus mirabilis. On the other hand, the results demonstrated that ezetimibe exhibited antibacterial activity against Staphylococcus aureus ATCC 33591, Staphylococcus aureus ATCC 43300, two of its clinical isolates, Escherichia coli ATCC 8739, and one of its clinical isolates. These findings were consistent with the MIC test results, with MIC values ranging between 128 and 256 µg/ml.

In conclusion, ezetimibe has a strong affinity for the PBP4 enzyme and shows promising potential as a treatment against bacterial infections. Thus, This study suggests developing various drug dosage forms of ezetimibe to repurpose its usage as antibacterial agent and to perform clinical trails for these pharmaceutical formulations to select the most appropriate dosage and delivery locations