Repositioning of Benzodiazepine Drugs and Synergistic Effect with Ciprofloxacin Against ESKAPE Pathogens

Abstract

Infectious diseases are among the leading causes of morbidity and mortality worldwide. Combating them becomes more complex when caused by the pathogens of the ESKAPE group, which are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. The purpose of this study was to investigate the repositioning potential of the benzodiazepines clonazepam and diazepam individually and in combination with the antibacterial ciprofloxacin against ESKAPE. The minimum inhibitory concentration and minimum bactericidal concentration against seven American Type Culture Collection (ATCC) reference standard strains and 64 ESKAPE clinical isolates were determined. In addition, the interaction with ciprofloxacin was determined by the checkerboard method and fractional inhibitory concentration index (FICI) of clonazepam against 11 ESKAPE and diazepam against five ESKAPE. We also list the results found and their clinical significance. Benzodiazepines showed similar antibacterial activity against Gram-positive and Gram-negative. The checkerboard and FICI results showed a synergistic effect of these drugs when associated with ciprofloxacin against almost all tested isolates. Viewing the clinical cases studied, benzodiazepines have potential as treatment alternatives. The results allow us to conclude that clonazepam and diazepam, when in combination with ciprofloxacin, have promising activity against ESKAPE, therefore, assuming the position of candidates for repositioning.