Meclizine and Cephalosporin Combination as Promising Antibiotic Drugs: Formulation, Antimicrobial, and In Silico Studies.

Cephalosporin is one of the antibiotics that are widely used because of its broad spectrum and high effectiveness. The aim of the present research was to formulate and evaluate the antimicrobial effect of meclizine (ME) alone and in combination with cefixime (CFM) and cefuroxime (CXM). Evaluation of antibacterial activities was determined by using Klebsiella (sensitive and ESBL), Escherichia coli, Staphylococcus aureus (sensitive and MRSA), and Pseudomonas aeruginosa. The molecular docking was conducted for ME and CFM with the crystal structure of beta-ketoacyl-acp synthase III + malonyl/CoA. The results show that ME has the highest minimum inhibitory concentrations (MICs) activity against sensitive Klebsiella spp., followed by sensitive S. aureus. The combination of ME and CXM demonstrated a synergistic activity against both sensitive and resistant S. aureus and sensitive Klebsiella with an interpretation of minimum bactericidal concentration (MBC) of < 0.06, 0.1875, and 0.33, respectively. Meanwhile, partial synergism activity is observed against E. coli, and indifference activity against P. aeruginosa and Klebsiella ESBL with an interpretation FBC of 0.75, 1.2, and 1.25, respectively. The ME and CFM combination showed partial synergism activity against sensitive Klebsiella, E. coli, and P. aeruginosa with an interpretation FBC of 0.625, 0.75, and 0.75, respectively. While indifference activity was recorded against both sensitive and MRSA S. aureus and Klebsiella ESBL with interpretation FBC of 4, 1.25, and 1.5, respectively. The ME and CXM combination showed the highest activity against Gram-positive bacteria and sensitive Klebsiella, while the ME and CFM combination showed the highest activity against Gram-negative bacteria. This combination may consider be a promising formula as an antimicrobial drug.