Comparison of methods for assessing synergic antibiotic interactions

Abstract

Twenty-five combined microtitre chequerboard/time kill curves were performed on ten isolates from patients with relapsing infection to assess the potential for combination therapy. The isolates were Burkholderia cepacia, Staphylococcus aureus and Klebsiella pneumoniae. No antagonism (FIC index or FBC index >4) was observed with any combination. Synergy by time kill curve (present in 21 combinations) was more often seen at 24 h than 2 or 5 h ( P<0.001). On comparing the mean of the FIC and FBC indices, there were significant differences in only four chequerboards ( P<0.05). The same checkerboard was repeated on 3 separate days to test reproducibility. There were no significant differences ( P>0.05). All combinations showing synergism by FBC index were synergic by FIC index. Synergy by FIC index predicted synergy by FBC index in 67%. All combinations showing synergism by FIC index were synergic by time kill at 24 h but there was poor correlation between synergy at 2 or 5 h and synergy by FIC index or FBC index. In conclusion combining time kill and chequerboard tests gives reproducible results and good correlation between FIC and FBC indices. FIC indices showing synergy were also predictive of synergy in time kill studies. For bactericidal combinations unlikely to be antagonistic, calculation of FIC index may be a good indicator of synergic bactericidal activity.