Investigation of the Antibacterial Synergistic Activity of Fosfomycin-Teicoplanin Combination in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Various Clinical Sample

Abstract

The aim of this study was to investigate the detection of teicoplanin and fosfomycin antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains by different methods and to evaluate the antibacterial synergistic effect of teicoplanin-fosfomycin combination by using checkerboard assay and time kill curve assay. Forty-five MRSA strains isolated from clinical samples in routine medical microbiology laboratory of G & ouml;ztepe Prof. Dr. S & uuml;leyman Yal & ccedil;in City Hospital were included in the study. In the first stage of the combination study, minimum inhibitory concentrations (MIC) were investigated by broth microdilution for teicoplanin and by both broth microdilution and agar dilution methods for fosfomycin. The combination of teicoplanin and fosfomycin was tested by the checkerboard method in 45 MRSA strains and combination effect was determined according to fractional inhibitory concentration index ( Sigma FIC) calculation. The synergistic effect and bactericidal activity of antibiotic combination were studied against a randomly selected strain from the strains used in the study by using time -kill method for 24 hours. As a result of teicoplanin and fosfomycin antibiotic susceptibility studies, all isolates were found to be susceptible to both antibiotics according to the susceptibility breakpoints determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A synergistic effect was found in 22 (49%), additive effect in 22 (49%) and indifferent effect in one (2%) of the 45 strains studied with the checkerboard method. The mean Sigma FIC of 45 isolates was found to be 0.5. In the combination study of the antibiotics of the isolate that was studied with time -kill method, synergism was detected for 1/8 MIC concentrations at 12 th hour and 24 th hour and synergism at 1/4 MIC concentration at sixth hour, 12 th hour and 24 th hour. In the combination study of 1/4 MIC concentrations of antibiotics, bactericidal effect was detected at sixth hour and this effect was observed to disappear at 12 th and 24 th hours. High rate of synergistic antibacterial effect of teicoplanin-fosfomycin combination on MRSA isolates was demonstrated as a result of in vitro tests. Such studies conducted on antibiotic -resistant bacterial infections will provide clinicians different treatment options and will contribute to increasing survival. As a result of this study, provided that it is supported by future clinical studies, it can be stated that the teicoplanin-fosfomycin combination may be an effective treatment option in community and hospital -acquired infections caused by MRSA.