The Study Of Synergistic Effect Of Artesunate In Combination With Penicillin Sodium Or Ceftriaxone Sodium On Various Bacteria

Objectives : In recent years, research shows that antibiotic resistance quickly spreads worldwide in ways: secretes extended spectrum β-lactamases or carbapenenm to hydrolyze antibiotics, gene mutation change medical targets, porin deficiency to avoid antibiotic permeation, the horizontal transfer of resistance genes between strains and the intrinsic active efflux pump to withstand efficacy, and lead to the bacteria(e.g. Staphylococcus aureus,Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli), which are only resistant even multidrug-resistant to antibiotics(e.g. aminoglycosides, penicillins,cephalosporins), and noteworthy, the R&D cycle of antibiotics are far less than the resistance rates of strains. So, in order to reverse the drug-resistance of strains, it confirm a simpler and more convenient way of finding drugs to enhance bacterial sensitivity to antibiotics. Through lots of literature review, artesunate not only has powerful antimalarial effect which can quickly control malaria episodes, and that has antibacterial effect, anti-inflammatory and antibacterial sensitization. Therefore, we make the following experiments to explore the potent medicinal value of the antibacterial effect of artesunate alone or supplementarily in hospital infection, which provide a certain experimental basis for effectively reducing the drug resistance caused by common clinical pathogenic bacteria in hospital infection by detection of antibacterial effect of artesunate synergy commonly antimicrobial agents such as penicillin sodium or ceftriaxone sodium on a variety of gram negative bacteria and gram positive bacteria.Methods: To observe the antibacterial effect of artesunate alone or in combination with penicillin sodium or ceftriaxone sodium which was as a combination of antibacterial drugs respectively on six strains such as Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Shigella, Pseudomonas aeruginosa ATCC27853 and clinical isolates in vitro bacteriostasis experiment using broth two-fold dilutions, and according with the experimentresults, the antibacterial effect and dynamic growth of Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Shigella, Pseudomonas aeruginosa ATCC27853 and clinical isolates to penicillin sodium or ceftriaxone sodium that concentration lower the MIC in absence or presence of artesunate of the minimum medicine concentration when that was divided above six strains into bacterial control group, penicillin sodium group, ceftriaxone sodium group, artesunate group, artesunate combined with penicillin sodium group and artesunate combined with ceftriaxone sodium group randomly was further observed to evaluate antibacterial sensitization effect of artesunate. Based on the comparison of the experiment results on antimicrobial properties of above six strains in vitro, the antibacterial effect of Pseudomonas aeruginosa ATCC27853 to ceftriaxone sodium alone or in combined with artesunate which were intramuscular injection in vivo was observed to find out mlD and sublethal bacteria of live Pseudomonas aeruginosaATCC27853 infection mice model. Then the blood bacteria, the serum LPS and IL-17 levels in mice challenged with sublethal live Pseudomonas aeruginosa ATCC27853 of artesunate combined with ceftriaxone sodium were observed to evaluate the antibacterial sensitization effect of artesunate on ceftriaxone sodium in mice.Results: Artesunate alone had faint bacteriostasis on six strains, but it could be coordinated with penicillin sodium to inhibit the growth of Bacillus subtilis and Pseudomonas aeruginosa clinical isolates, and increased the antibacterial susceptibility of Shigella,Pseudomonas aeruginosa ATCC27853 and clinical isolates to ceftriaxone sodium, which could significantly slow bacterial growth rate in the presence of antibiotics compared with penicillin sodium or ceftriaxone sodium alone. And the inhibition of blood bacteria number and serum LPS and the promotion of serum IL-17 were observed when artesunate in combined with ceftriaxone sodium, and that was better than that of artesunate or ceftriaxone sodium alone in vivo.Conclusion: Artesunate can significantly enhance the sensitivity on Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Pseudomonas aeruginosaATCC27853 and clinical isolates in combined with penicillin sodium or ceftriaxone sodium, and the synergistic inhibition of artesunate in combination with ceftriaxone on Pseudomonas aeruginosa was the best. Upon closer inspection, blood bacteria number, serum LPS and IL-17 levels aresynergistically decreased or increased of artesunate in combined with ceftriaxone sodium compared with artesunate alone or ceftriaxone sodium alone. These research results provide new experimental basis for the reversal of the widespread drug resistance on Pseudomonas aeruginosa in nosocomial infection and the increasing of artesunate new usage pharmacologically.