Synergy of a Novel Antibiotic Adjuvant Entity against Multi Drug Resistant Enterobacteriaceae

In the present investigation, we investigated the in vitro interaction of ceftriaxone plus sulbactam with disodium edetate, a Non Antibiotic Adjuvant (NAA) against selected clinical isolates and in vitro susceptibility studies were also performed. The isolates were tested against a range of ratios of ceftriaxone and sulbactam using a microdilution checkerboard method. Having determined the appropriate ratios of ceftriaxone plus sulbactam, effect of various concentration of disodium edetate were also studied using the microdilution checkerboard method. All the results were analysed with the Fractional Inhibitory Concentration (FIC) indices. Susceptibility studies were carried out according to the Clinical and Laboratory Standards Institute (CLSI) methods. Results of this study demonstrated that 2:1 ratio of ceftriaxone and sulbactam was the more synergistic with FIC index values 0.4281, 0.4023, 0.4124 and 0.4325 for E. coli, A. baumannii, P. aeruginosa and K. pneumoniae. The synergicity of ceftriaxone and sulbactam was enhanced significantly with increasing concentration of disodium edetate and produced the lowest FIC index (<0.2) at 10 mM of disodium edetate in all positive controls as well as clinical isolates. Further, the synergy between ceftriaxone plus sulbactam with disodium edetate (Elores) was confirmed by broth dilution, time kill curve and agar diffusion methods. In broth dilution method, Elores (ceftriaxone+sulbactam+disodium edetate) produced 4 to 5 fold lower MIC when compared with ceftriaxone plus sulbactam. Approximately 10 log of killing reduction was observed with synergistic ratio of Elores in time kill curve study. This study suggest that Elores could be an alternative regimen in combating antibiotic resistance among multi drug resistant Enterobacteriaceae.