The usefulness of in vitro sensitivity tests in antibiotic therapy.

Abstract

INTRODUCTION With the advent of antimicrobial agents twenty-five years ago, the course of many infections has been profoundly altered since these agents have often enabled the normal defense mechanism of the body to be by­ passed. However, the enthusiasm and widespread use that followed the introduction of each new drug was gradually tempered by the knowledge that these drugs, by virtue of their ability to influence the host-parasite relationship, could exert harmful as well as beneficial effects. Further, it became obvious that certain criteria were required for the intelligent use of these antimicrobial agents. The rational use of antibacterial drugs should be based upon two prin­ ciples. First, the specific identity of the infecting organism must be de­ termined. Second, a test must be devised which will provide an accurate estimate that the antibiotic will be effective in vivo. An obvious solution to the latter problem is to assess the activity of a drug in experimental infec­ tions in animals. However, the response of these infections to antibiotics has been a notoriously unreliable guide to the treatment of human disease. In addition, this method is expensive, cumbersome, and does not lend itself readily LO use on a large scale. Therefore, efforts were channeled into the development of in vitro sensitivity tests and their application to clinical infections. One of the earliest methods attempting to apply in vitro tests to clinical situations involved comparison of the infecting organism with a standard strain of known susceptibility. This has been largely supplanted by tests based on a comparison of antibiotic concentration in body fluids with the minimal concentration of the drug necessary to inhibit growth of the organism in vitro. By definition, then, an organism is not considered sensitive unless the concentration of antibiotic attainable in the body ex­ ceeds that necessary to inhibit its growth in vitro (1). Several objections may be raised to this definition of sensitivity. First, local or humoral host defense mechanisms may act in synergism or antago-