Streptomycin, an aminoglycoside antibiotic (see Chapter 46), was the first drug shown to reduce tuberculosis mortality. Streptomycin is bactericidal against M. tuberculosis in vitro but is inactive against intracellular organisms. Most M. tuberculosis strains and nontuber-culosis species, such as M. kansasii and M. avium-intracellulare, are sensitive. Spontaneous resistance to streptomycin, seen in approximately 1 in 106 tubercle bacilli, is related to a point mutation that involves the gene (rpsl or rrs) that encodes for ribosomal proteins and binding sites. About 80% of strains that are resistant to isoniazid and rifampin are also resistant to streptomycin.
Streptomycin is indicated as a fourth drug in combination with isoniazid, rifampin, and pyrazinamide in patients at high risk for drug resistance. It is also used in the treatment of streptomycin-susceptible MDR tuberculosis.
Ototoxicity and nephrotoxicity are the major concerns during administration of streptomycin and other aminoglycosides. The toxic effects are dose related and increase with age and underlying renal insufficiency. All aminoglycosides require dose adjustment in renal failure patients. Ototoxicity is severe when aminoglyco-sides are combined with other potentially ototoxic agents.
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