ANTIMICROBIAL EFFECT OF HIGH DOSE ASCORBATE IN MOUSE MODEL WITH BACTERIAL INFECTION

Abstract

Ascorbate or Vitamin C is a vitamin that is important to the body. It contributes to the immunity, involves the collagen formation, acts as an antioxidant and has the ability to destroy cancer cells and bacteria. These abilities depend on the concentration of ascorbate. Bactericidal properties of ascorbate were interesting, especially in the high concentrations. Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli are a common etiologies of nosocomial infection in Thailand and worldwide. These bacteria have developed mechanisms of antibiotics resistance and cause more violence in the disease. Hence, the time-killing assay was used to explore the bactericidal synergy of ascorbate in the administration with ceftriaxone, a common antibiotic. The results showed that ascorbate concentrations of 10 and 40 millimolar (mM) with ceftriaxone at the concentration of minimal inhibitory concentration (1X MIC) could inhibit the growth of S. aureus (ATCC strain) both in in vitro and in vivo but not effective against P.aeruginosa, A. baumannii and E.coli. In addition, ascorbate alone at 250mM could inhibit the growth of S. aureus and P. aeruginosa. Moreover, ascorbate 10 and 40 millimolar can increase macrophage killing activity to S. aureus and P. aeruginosa. In parallel, MRSA clinical strains were tested with the time-kill assay in vitro for the prediction of the in vivo clinical responses in S. aureus-induced myositis mouse model. Indeed, the synergy in the time-kill assay of ascorbate plus ceftriaxone associate with the favorable outcome in myositis model. In conclusion, ascorbate antibiotic synergy against S. aureus-induced myositis was predictable by the time kill assay. This method might be valuable to select the patients potentially benefit from Ascorbate-adjuvant therapy, especially, against the antibiotic-resistant bacteria.