Detection ofin vitro activity of new benzimidazole derivatives on carbapenem-resistant gram-negative rods of clinical importance

Carbapenems are broad-spectrum β-lactam antibiotics that are considered the last antibiotic used especially for the treatment of critically ill patients and/or infections caused by antimicrobial-resistant Gram-negative bacteria. However, the increasing resistance to carbapenems has led to the search for new treatment options. The World Health Organization draws attention to three pathogens, especially carbapenem-resistant Acinetobacter baumanni, Klebsiella pneumonia and E. coli, and reports that these resistant pathogens will cause serious health problems in the coming years. Therefore, the search for new antibiotics and the modification of existing ones for improvement is one of the main concerns of modern medicine. Benzimidazole can act as a bioisostere for purine, which is crucial for bacterial cell wall, nucleic acid and protein biosynthesis. In addition, benzimidazole drugs in clinical use have an established safety and efficacy profile. Therefore, when the literature is reviewed, it is seen that there is a design of additional benzimidazole derivatives with antimicrobial activity by examining the effect of a number of different functional groups. For this reason, in our study, which is a pilot study, it is aimed to determine the in vitro antimicrobial activity of new benzimidazole derivatives with different structures on carbapenem resistant and susceptible strains isolated from clinical specimens by broth microdilution method. The effects of benzimidazole derivatives, whose MIC values were determined by the broth microdilution method, will be compared with the MIC values to be determined in carbapenem-susceptible strains. It was found that the S1 molecule was relatively more effective than S2 on KD E. coli clinical isolates, but the S3 molecule had a very low bacteriostatic effect. However, in KR E. coli isolates, it was determined that the S1 molecule had a stronger bacteriostatic effect than S2, and the S3 compound had no effect. While the antibacterial activities of S1 and S2 molecules against KR K. pneumonia strains are close to each other, it has been shown that the activity of S3 is low in this bacterial group and more effective at higher concentrations (MIC: 800 μg/mL). While antibacterial activities of S1 and S2 compounds were found to be close in both KR and KD A. Baumannii isolates, S3 compound did not show any effect against these strains. Based on the data to be obtained at the end of the study, it is aimed to obtain an alternative antimicrobial agent for carbapenem resistant gram negative rods.