An inevitable consequence of the development of a variety of chemotherapeutic agents was the combination of two or more drugs as a means of broadening the chemotherapeutic effect. When confronted with a mixed infection in which a single antibiotic did not inhibit all the bacteria, the need for adding a second antibiotic to increase the antibacterial spectrum was self-evident. However, the treatment of an infection due to a single agent required a distinctly different rationale. Many workers on an empirical basis reported that in the treatment of experimental infections due to a single infectious agent two drugs were more effective than either agent alone. However, these results often were misleading, for in order to demonstrate a combined effect one had to
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