STREPTOMYCIN
The typical adult dose
is 1 g/d (15 mg/kg/d). If the creatinine clearance is less than 30 mL/min or
the patient is on hemodialysis, the dose is 15 mg/kg two or three times per
week. Most tubercle bacilli are inhibited by streptomycin, 1–10 mcg/mL, in
vitro. Nontuberculosis species of mycobacteria other than Mycobacterium avium complex (MAC) and Mycobacterium kansasii are resistant. All large populations of
tubercle bacilli contain some streptomycin-resistant mutants. On average, 1 in
108 tubercle bacilli can
be expected to be resistant to streptomycin at levels of 10–100 mcg/mL.
Resistance is due to a point mutation in either the rpsL gene encoding the S12 ribo-somal protein gene or the rrs gene encoding 16S ribosomal rRNA,
which alters the ribosomal binding site.
Streptomycin
penetrates into cells poorly and is active mainly against extracellular
tubercle bacilli. Streptomycin crosses the blood-brain barrier and achieves
therapeutic concentrations with inflamed meninges.
Streptomycin sulfate
is used when an injectable drug is needed or desirable and in the treatment of
infections resistant to other drugs. The usual dosage is 15 mg/kg/d
intramuscularly or intravenouslydaily for adults (20–40 mg/kg/d, not to exceed
1–1.5 g for chil-dren) for several weeks, followed by 1–1.5 g two or three
times weekly for several months. Serum concentrations of approximately 40
mcg/mL are achieved 30–60 minutes after intramuscular injec-tion of a 15 mg/kg
dose. Other drugs are always given in combina-tion to prevent emergence of
resistance.
Streptomycin is
ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse
effects and may be permanent. Toxicity is dose-related, and the risk is
increased in the elderly. As with all aminoglycosides, the dose must be
adjusted according to renal function . Toxicity can be reduced by limit-ing
therapy to no more than 6 months whenever possible.
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