Microcalorimetric study of the effects of cephalexin and cephaloridin on Escherichia coli and Staphylococcus aureus.

Abstract

The kinetics of the antibacterial actions of cephalexin and cephaloridin against a strain of Escherichia coli and a strain of Staphylococcus aureus were studied by a flow microcalorimeter. The heat production was related to the number of viable organisms (CFU ml-1), the pH, the optical density of the culture medium (OD540), and the morphology of the antibiotic-exposed bacteria. No heat effects could be registered when the number of CFU was below 10(4) ml-1. The addition of cephalexin, 2.5 microgram ml-1 (5 x MIC), to cultures of S. aureus caused a decrease in the heat production which was only roughly correlated with the number of CFU ml-1. This was also the case when 9.0 microgram ml-1 (2 x MIC) of this drug were added to cultures of E. coli. Two to three hours after the drugs had been added, no heat effects could be registered for the following 6--8 hours, after which an increase in the heat production again occurred. The MIC and MBC of the organisms isolated during this late heat increase were 8--40 times higher than those of the parent test organisms. A direct relation between drug concentration and response, i.e. heat effects produced, was found when increasing concentrations of cephalexin, i.e. 1.0 up to 50 micrograms ml-1 (2--100 x MIC) were added in the logarithmic growth phase to cultures of S. aureus. In ampoule calorimetric experiments, E. coli was cultured in a non-aerated, sealed growth vessel in the presence of cephalexin or cephaloridin in concentrations corresponding to 1/2 x MIC. The thermograms did not differ in shape, although the heat effects occurred somewhat later in the culture containing cephaloridin.