The introduction of a novel antibiotic or antibaoterial
agent into clinical practice is the culmination of several years
work by relatively large numbers of specialists in widely different
fields of science. The details of the testing procedures employed
in the selection of the compound of choice from a large number of
candidates will vary, depending upon the nature of the substance
being evaluated, but the general principles remain the same.
Thus, although the final proof of the value of an anti¬
baoterial agent is the olinical result obtained when the drug is used
to treat infection it is clearly impracticable to evaluate new drugs
by clinical trial alone. Consequently, the therapeutio potential of
a novel antibiotic must be assessed by study of seleoted parameters in
the laboratory. These include measurement of antibaoterial activity
in vitro and in vivo, and studies of the absorption, distribution and
metabolism of the drug in animals and healthy volunteers. The
toxicology of the compound is also of great importance and is a factor
which calls for the generation of vast amounts of data from animal
In addition to the evaluation data generated during the
selection or assessment procedures, other parameters are of importance.
For instance, knowledge of the interaction of the test compound with
other available drugs, of the mode of action, and of the rate of
development of resistance, provides information to be considered in
the assessment of activity. Moreover, the potential value of a
compound whioh is in clinical use may be greatly affected by the
emergence of resistant bacteria and understanding of this is important
as part of ongoing evaluation.
The sections below illustrate the factors involved in the
laboratory evaluation of new antibiotics and in the assessment of
the therapeutic potential of these drugs, by reference to experi¬
mental data obtained in my laboratory in investigations with novel
penicillins or other antibacterial substances.