Microcalorimetry as a tool for evaluation of antibacterial effects of doxycycline and tetracycline

The heat effects produced by a strain of Escherichia coli in the presence of doxycycline and tetracycline were determined by calorimetric measurements using batch and flow microcalorimeters of the heat-conduction type. There was a clear difference in the capacity of the two tetracyclines to suppress the metabolism of the test bacterium as indicated by the heat production registered. In the presence of doxycycline or tetracycline in a concentration of 0.4 mug/ml (half the minimum inhibitory concentration, MIC), the time interval between the start of the experiment and a heat production of 2 muW/ml was 4.5 h for tetracycline and 7.3 h for doxycycline. When the antibiotics, in a concentration of 1.6 mug/ml (2 X MIC), were added to the culture during the logarithmic growth phase, tetracycline depressed heat production much less than doxycycline. Almost immediately after the addition of the two tetracyclines studied, heat production decreased sharply. The heat production rose again 1 h after tetracycline had been added, but remained at a low level for at least 16 h after doxycycline.--The results suggest that there are differences in the kinetics of the antibacterial action of doxycycline and tetracycline. Microcalorimetric studies provide new information for determining antibacterial activities of antibiotics, information that cannot be obtained by means of conventional bacteriological techniques. Such studies might be of value for the establishment of optimal dose regimens.