The activity of chemotherapeutic agents

Studies conducted in vitro have contributed considerable information regarding the quantitative aspects of the problem of the action of chemotherapeutic agents on microorganisms. McIntosh and Whitby (1939), Chandler and Janeway (1939), Bullowa, Osgood, Bukantz and Brownlee (1940) and others have pointed out that there appears to be a quantitative relationship between the effective bacteriostatic concentration of a chemo-therapeutic agent and the number of bacteria. However, most of the methods employed in studying the in vitro action of drugs do not lend themselves to a precise evaluation of the results because of their inherent errors. For example, plate counts cannot be relied on to demonstrate small differences in bacterial populations. It will be shown subsequently that small differences in population numbers may be of importance in interpreting the effects of drugs on susceptible microorganisms during the first two to four hours of incubation. One of the characteristics of a chemotherapeutic agent is its bacteriostatic or bactericidal action on susceptible organisms in vitro. Whether the action is bacteriostatic or is bactericidal appears to depend on the environmental conditions. Under favorable growth conditions the apparent effect is a slowing in the rate of increase, whereas under unfavorable conditions the effect is apparently bactericidal. It will be pointed out later that the data presented in this paper may be interpreted as indicating that the action of the drug is bactericidal even though the organ-isms are grown in a favorable media. It is the purpose of this report to present in detail a simple and rapid method for studying and demonstrating the in vitro activity of chemotherapeutic agents and interpreting the data thus obtained