History and development of antimicrobial susceptibility testing methodology.

Antimicrobial susceptibility testing (AST) is performed daily on bacterial isolates in clinical laboratories. The techniques employed are often taken for granted. This paper traces the history and development of some methods still in common use for routine AST, e.g. disc diffusion and agar dilution. It was quickly recognized by early investigators that there were many variables affecting the results of these tests. Consequently, there was recognition (as early as the late 1950s) that standardization of these techniques was required. This need has led to many organizations producing standardized AST methodologies. Although some disc diffusion techniques that generated results within 4-6 h were described, most relied on 18-24 h incubation before a result was available. The clinical and economic pressures for rapid methods with low labour input led to the development of semi-automated and automated AST methodologies in the 1970s. Until 10 years ago, AST techniques relied on phenotypically testing the bacteria isolated. However, to increase the speed and reliability of resistance testing, the use of a genotypic approach has been advocated. The limitations and benefits of this new approach are discussed.

Forty years of screening programmes for antibiotics.

The article gathers the reflections on the experiences of forty years doing research on the screening of natural product in the pharmaceutical industry. Over those years new technologies have improved the methodology. However, the steps followed in such a research are the same: the isolation and cultivation of microorganisms; the definition of assays with well defined targets; the demonstration of their efficacy for the discovery and selection of active substances produced by microorganisms; the classification and structural determination of the new products; and the study of their therapeutical efficiency. Examples of the processes which led to the production of several antibiotics (fosfomycin, cefoxitin and thienamycin) are described. One important lesson that the author has learnt is that microorganisms have unique fingerprints and that generalization should be avoided in the planning of this work.