Resistance to antitubercular drugs.

Abstract

Historians established the existence of endemic tuberculosis from Egyptian mummies dating from 2000 to 4000 B.C. (reviewed by Bloom and Murray, 1992). Tuberculosis was prevalent in Europe throughout the middle ages. Newly crowned kings of England and France were believed to have special healing powers and the most desired treatment of tuberculosis was being touched by these kings. Tuberculosis was responsible for 20% of all deaths in London in 1651, and the disease may have accounted for a third of all deaths in Paris in the 19th century. As Europeans colonized the Americas and sub-Saharan Africa, the disease was passed to susceptible populations and spread worldwide (Young et al 1996). In 1882, Robert Koch identified an acid-fast bacterium, Mycobacterium tuberculosis, as the causative agent of tuberculosis (Koch, 1932). His criteria for proof that the organism he discovered caused tuberculosis have been widely adopted and have become known as Koch’s postulates: isolation of the bacilli from the body, growth in pure culture, and reproduction of the same “morbid” condition by administering the isolated bacilli to animals. In 1908, the BCG (bacille Calmette-Guerin) vaccine was first used to immunize a patient, and is currently the most widely used vaccine in the world. Discovery of the antibacterial activity of prontosil in 1935 by Gerhard Domagk marked a fundamental change from pathogen-specific therapy to non-pathogen-specific therapy that allowed prompt and effective treatment of bacterial infections without the necessity of identifying the pathogens involved (Casadevall, 1996). The discovery of the antibacterial and antitubercular properties of streptomycin in 1944 (Schatz and Waksman), and both isoniazid and pyrazinamide in 1952 (Kushner et al.; Middlebrook), led to effective chemotherapies that decreased tuberculosis mortality rates in the United States and worldwide.