Kinetics of the actions of tetracyclines on Escherichia coli as studied by microcalorimetry

Microcalorimetry was used to study the kinetics of the actions of various tetracyclines on a strain of Escherichia coli. Differences in the capacity to suppress the metabolism of this bacterium were observed. When the antibiotic was present from the start of the experiment, a heat production of 2.0 muW/ml was registered after 12.5 h using minocycline; the corresponding figures for doxycycline, oxytetracycline, and tetracycline were 7.3, 6.6, and 4.5 h, respectively. In these experiments, equal concentrations, i.e., half the minimum inhibitory concentration (MIC), of each drug were used. The MIC for all the tetracyclines tested, determined by the broth dilution technique, was 0.8 mug/ml. In other experiments, the antibiotic (concentration, 1.6 mug/ml = 2x MIC) was introduced into the growth vessel during the logarithmic growth phase of the organism. The extent and duration of the inhibitory effect on the metabolism, as judged from the decrease in heat production, varied with the different tetracyclines. Immediately after introduction, minocycline, doxycycline, oxytetracycline, and tetracycline decreased the heat production in decreasing order of potency. With tetracycline, the heat production rose after about 1 h, and with minocycline it rose after about 9 h. The heat production remained at a low level for at least 19 h when using doxycycline and oxytetracycline. The results indicate that microcalorimetry offers a means for studies of the kinetics of the antibacterial actions of antibiotics and provides information that cannot be obtained by conventional bacteriological techniques. This information may be of use, in conjunction with pharmacokinetic data, in establishing optimum doses and dose intervals in antibiotic therapy.