Unravelling the 'tangled web': chemotherapy for tuberculosis in Britain, 1940-70 the William Bynum prize essay.

The introduction and assimilation of chemotherapy to treat pulmonary tuberculosis (TB) during the mid-twentieth century appears at first sight to be a success story dominated by the use of streptomycin in a series of randomised clinical trials run under the auspices of the Medical Research Council (MRC). However, what this standard rhetoric overlooks is the complexity of TB chemotherapy, and the relationship between this and two other ways of treating the disease, bed rest and thoracic surgery. During the late 1940s and 1950s, these three treatment strands overlapped one another, and determining best practice from a plethora of prescribing choices was a difficult task. This article focuses on the clinical decision-making underpinning the evolution of successful treatment for TB using drugs alone. Fears over the risk of streptomycin-resistant organisms entering the community meant that, initially, the clinical application of streptomycin was limited. Combining it with other drugs lessened this risk, but even so the potential of chemotherapy as a curative option for TB was not immediately apparent. The MRC ran a series of clinical trials in the post-war period but not all of their recommendations were adopted by clinicians in the field. Rather, a range of different determinants, including the timing of trials, the time taken for results to emerge, and whether these results 'fitted' with individual experience all influenced the translation of trial results into clinical practice.

History of antibiotics. From salvarsan to cephalosporins.

Infections have represented for a long time the leading cause of death in humans. During the 19th century, pneumonia, tuberculosis, diarrhea and diphtheria were considered the main causes of death in children and adults. Only in the late 19th century did it become possible to correlate the existence of microscopic pathogens with the development of various diseases. Within a few years the introduction of antiseptic procedures had begun to reduce mortality due to postsurgical infections. Sanitation and hygiene played a significant role in the reduction of the mortality due to several infectious diseases. The introduction of the first compounds with antimicrobial activity succeeded in conquering many diseases. In this review we analyzed, from a historical perspective, the development of antibiotics and the circumstances that led to their discovery. The first compound with antimicrobial activity was introduced in 1911 by Erlich. He focused his research activity on the discovery of a "magic bullet" to treat syphilis. Afterwards, Foley and colleagues brought penicillin to the forefront. Streptomycin represents the first drug discovered for the treatment of tuberculosis, and its development included the first use of clinical trials. Finally, with the development of cephalosporins, the introduction of new antimicrobial compounds with broad activity against gram-positive and also some gram-negative bacteria began.

The classic. Streptomycin in tuberculous bone and joint lesions with mixed infection and sinuses.

At the present time, streptomycin represents a tremendous advance in the treatment of patients with these lesions. Streptomycin undoubtedly will be improved upon and superseded by some other agent in the future, giving us better control of this disease and possibly enabling us to eradicate it. In closed lesions streptomycin, in dosages of 90 grams in a period of 90 days, has failed to arrest the tuberculous process permanently. Failure of treatment with streptomycin suggests strongly the presence of a sequestrum, a thick-walled abscess, or inadequate surgery. Healing seems to be related to the duration of administration of streptomycin and not to the total dosage. In patients having sinuses, streptomycin should be continued after healing for a period at least half as long as the healing period itself. Surgical ankylosis, or resection of non-weight-bearing joints, is apparently as necessary now as it ever has been, but is much safer and more effective. Indeed, at times surgical attack is made possible only by the use of streptomycin.