Spectrophotometric assessment of dose-response curves for single antimicrobial agents and antimicrobial combinations

The activity of single antimicrobial agents and antimicrobial combinations was examined by measuring their effects on the growth rate constant of a test strain of Escherichia coli. This spectrophotometric method provides a kinetic view of antimicrobial action and is sufficiently precise to define dose-response curves, in contrast to standard methods such as broth or agar dilution testing, which are static and measure only all-or-none responses. The results demonstrate that dose-response curves for single antimicrobial agents are logarithmic (rather than linear) and that the effects of antimicrobial combinations may be exquisitely concentration dependent. Although the results for some antimicrobial combinations were similar with the spectrophotometric and checkerboard methods, other combinations produced different results in the two systems. Additional studies will be necessary to determine whether one or the other of these methods more accurately predicts clinical outcome.