ABSTRACT

The use of antibiotics has had a dramatic effect on the practice of medicine, the pharmaceutical industry, and microbiology. Prior to the discovery of antibiotics, the treatment of infectious diseases was empirical. Various types of antimicrobial agents, including extract of plants, fungi, and lichens have been employed for thousands of years in primitive populations without any scientific knowledge of what the active compounds were. However, the seminal work of Joseph Lister, Louis Pasteur, Robert Koch, and others, identifying microbes as agents of disease and devising means for avoiding infections by the use of disinfectants and antiseptics, made possible rational approaches for treatment of infectious diseases. True antimicrobial therapy became available only in the 1930s with the discovery of the sulfonamides by Gerhardt Domagk. Subsequently, those synthetic agents were found to be competitive inhibitors of the enzymatic incorporation of p-aminobenzoic acid into the folic acid biosynthetic pathway. Thus, the sulfonamides became the first targets of early attempts for rational drug modification. Surprisingly, no infectious disease has been eliminated by the use of antibiotics. Thus, most of the bacteria that caused human suffering prior to 1950 are still causing illness, and we have come to the woeful realization that the use of antibiotics has even contributed to the recent phenomenon of emerging infections.