Interventions for Tuberculosis Control and Elimination 2002

orne out by experiments which have demonstrated its activity against bacilli
residing inside macrophages as well. 396
Streptomycin inhibits protein synthesis of M. tuberculosis. Streptomycin
acts on ribosomes and causes misreading of the genetic code, inhibition of
translation of mRNA, and aberrant proofreading. 397
It was demonstrated a half century ago that a strain may contain different
variants with different levels of susceptibility (or resistance) to streptomycin.
398 Interestingly, problems with molecular techniques to properly
identify clinically relevant resistance led some authors to conclude that the
seemingly outdated use of drug-containing media described in these early
reports 398 may again become a valid procedure. 399 Resistance results from
a limited number of missense mutations in the rrs gene (16S rRNA) or in
the rpsL gene (ribosomal protein S12). 400
The maximum proportion of streptomycin resistant mutants able to
grow during streptomycin monotherapy of an isoniazid susceptible strain is
estimated to be approximately 1 in 10 8 . 53
Pharmacokinetics. Streptomycin is not at all, or only insignificantly,
absorbed from the gut and its administration is parenteral. Following intramuscular
administration, resorption is rapid and maximum serum concentrations
are achieved within one to two hours (figure 24). 183,401 Streptomycin,
like all aminoglycosides, is excreted by glomerular filtration. When kid-
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Figure 24. Pharmacokinetics of streptomycin in tuberculosis patients. Reproduced
from183 by the permission of the publisher American Thoracic Society at the
American Lung Association.
43