Trimethoprim/Sulfamethoxazole: An Overview

Abstract

The antibacterial chemotherapeutic era, which has dominated much of medicine in the past 50 years, was really initiated by the introduction of the sulfonamides in 1932 (see Domagk 1935). After widespread and effective use of sulfonamides in a variety of infectious diseases, resistant organisms began to emerge, at first slowly, but then with frightening rapidity. In Japan, for example, species of Shigella were invariably sensitive to sulfonamides in the mid 1940 s, but by early 1952 were just as invariably resistant. Fortunately, or so it was naively thought at the time, newer drugs were introduced to which the organisms were susceptible, including tetracycline, chloramphenicol, and streptomycin, and therapy once again became possible. However, over the next 5 years there emerged organisms resistant to each of these agents, and of greater importance, to several of them at the same time. By 1957 it was observed that an initially sulfonamide-resistant but otherwise sensitive isolate in a patient treated with just one of the agents, would suddenly appear with the resistance pattern of sulfonamide, streptomycin, tetracycline, and chloramphenicol. Akiba et al. (1960) and Ochiai et al. (1959) independently suggested that the information mediating such one-step resistance might be transferred from bacteria to bacteria, and proceeded to demonstrate this in vitro. In this fashion the world of transferable drug resistance (R factors) and the biology of extrachromosomal deoxyribonucleic acid, plasmids, was opened to the eyes and the minds of scientists. The past two decades of the chemotherapeutic era have been dominated as much by transferable drug resistance as by the introduction of new and potent drugs or combinations such as trimethoprim/sulfamethoxazole (TMP/SMX, Cotrimoxazole, Bactrim, Septrin, Septra). In this chapter, we will present an overview of TMP/SMX as a guide to the detailed information to follow and as a perspective for clinical thinking in current and future use of the drug or its individual components.