Abstract
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 104 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.
Highlights
Salmonella species getting resistant to expandedspectrum cephalosporins have been reported in severalIncreasing resistance to 3rd generation countries, including Argentina, Turkey, Algeria, Saudi cephalosporins particlularly due to extended spectrum Arabia, Greece, Tunisia and France (Dutil et al, 2010).beta lactamase production has become a major concern In addition, most of the bacteria, responsible for especially among Enterobacteriaceae that cause community-acquired infections have developed nosocomial infections (Rawat and Nair, 2010). resistance to many antibacterial agents beta-Approximately 20% of Klebsiella pnenumoniae lactams which are being used in over 50% of all systemic infections and 31% of Enterobacter species infections in antibiotics (Acevedo et al, 2009)
Results of this study demonstrated that 2:1 ratio of ceftriaxone and sulbactam was the more synergistic with Fractional Inhibitory Concentration (FIC) index values 0.4281, 0.4023, 0.4124 and 0.4325 for E. coli, A. baumannii, P. aeruginosa and K. pneumoniae
This study suggest that Elores could be an alternative regimen in combating antibiotic resistance among multi drug resistant Enterobacteriaceae
Summary
Salmonella species getting resistant to expandedspectrum cephalosporins have been reported in severalIncreasing resistance to 3rd generation countries, including Argentina, Turkey, Algeria, Saudi cephalosporins particlularly due to extended spectrum Arabia, Greece, Tunisia and France (Dutil et al, 2010).beta lactamase production has become a major concern In addition, most of the bacteria, responsible for especially among Enterobacteriaceae that cause community-acquired infections have developed nosocomial infections (Rawat and Nair, 2010). resistance to many antibacterial agents beta-Approximately 20% of Klebsiella pnenumoniae lactams which are being used in over 50% of all systemic infections and 31% of Enterobacter species infections in antibiotics (Acevedo et al, 2009). Beta lactamase production has become a major concern In addition, most of the bacteria, responsible for especially among Enterobacteriaceae that cause community-acquired infections have developed nosocomial infections (Rawat and Nair, 2010). In recent years, these organisms have been reported to be resistant to these commonly used antimicrobial agents worldwide (Chaudhary and Payasi; 2012; Memish et al, 2012; Muthusamy and Boppe, 2012). Acquisition or expression of Metallo-β-Lactamases (MBLs), Extended-Spectrum β-Lactamases (ESBLs), decreased permeability, overexpression of efflux pump are thought to be the main factors contributing to antibiotic resistance development (Chaudhary and Payasi, 2012; Zavascki et al, 2010; Karthika et al, 2009)
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