Interventions for Tuberculosis Control and Elimination 2002

Council 122 or the individual trials conducted by the US Public Health
Service 319,479-491 might be consulted.
Streptomycin monotherapy
Shortly after the discovery of streptomycin, clinical trials with streptomycin
monotherapy were conducted in Great Britain 465 and the United States. 492
It was noted in these trials that case fatality from tuberculosis was considerably
reduced. However, it was also seen that patients improved over
the first few months and subsequently deteriorated, in many cases due to
acquisition of streptomycin resistance. Among survivors, sputum conversion
did not much differ between those receiving streptomycin and those
not (figure 42). 492 The insoluble problem was the selection of resistant
strains. While toxicity could be reduced by lowering the dosage and spacing
administration more widely, the problem of bacterial resistance was not
resolved. 493 The streptomycin trials impacted considerably on research for
the next 20 years, which largely concentrated on methods of preventing the
emergence of drug resistance.
Streptomycin plus para-aminosalicylic acid
The introduction of para-aminosalicylic acid into the armamentarium allowed
combination therapy to be used. In a study of the British Medical Research
Per cent positive
100
80
60
40
20
0
0 3 6 9 12
Month of treatment
61
Placebo
Streptomycin
Figure 42. Sputum culture conversion among patients receiving streptomycin compared
to placebo. 492