Streptomycin
Indications
Streptomycin is indicated for the treatment of individuals with moderate to severe infections caused by susceptible strains of microorganisms in the specific conditions listed below:
Mycobacterium tuberculosis: The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Center for Disease Control recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. In the past when the national rate of primary drug resistance to isoniazid was known to be less than 4% and was either stable or declining, therapy with two and three drug regimens was considered adequate. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered. Streptomycin is also indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. The management of tuberculosis has become more complex as a consequence of increasing rates of drug resistance and concomitant HIV infection. Additional consultation from experts in the treatment of tuberculosis may be desirable in those settings.
Non-tuberculosis infections: The use of streptomycin should be limited to the treatment of infections caused by bacteria which have been shown to be susceptible to the antibacterial effects of streptomycin and which are not amenable to therapy with less potentially toxic agents.
Mycobacterium tuberculosis: The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Center for Disease Control recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. In the past when the national rate of primary drug resistance to isoniazid was known to be less than 4% and was either stable or declining, therapy with two and three drug regimens was considered adequate. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered. Streptomycin is also indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. The management of tuberculosis has become more complex as a consequence of increasing rates of drug resistance and concomitant HIV infection. Additional consultation from experts in the treatment of tuberculosis may be desirable in those settings.
Non-tuberculosis infections: The use of streptomycin should be limited to the treatment of infections caused by bacteria which have been shown to be susceptible to the antibacterial effects of streptomycin and which are not amenable to therapy with less potentially toxic agents.
- Pasteurella pestis (plague)
- Francisella tularensis (tularemia)
- Brucella
- Calymmatobacterium granulomatis (donovanosis, granuloma inguinale)
- H. ducreyi (chancroid)
- H. influenzae (in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agent)
- K. pneumoniae pneumonia (concomitantly with another antibacterial agent)
- E.coli, Proteus, A. aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections
- Streptococcus viridans, Enterococcus faecalis (in endocardial infections - concomitantly with penicillin)
- Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent)
Pharmacology
Aminoglycosides like Streptomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Streptomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.
Dosage & Administration
Tularaemia:
- Adult: 1-2 g daily in divided doses for 7-14 days until the patient is afebrile for 5-7 days.
- Child: 15 mg/kg bid for at least 10-14 days. Max: 2 g daily
- Adult: Streptococcal endocarditis: 1 g bid for 1 wk, then 500 mg bid for the 2nd wk. Enterococcal endocarditis: 1 g bid for 2 wk then 500 mg bid for an additional 4 wk. Doses are given in combination with penicillin.
- Child: Enterococcal endocarditis: 20-30 mg/kg daily in 2 divided doses, in combination w/ penicillin.
- Elderly: Streptococcal endocarditis: >60 yr 500 mg bid for the entire 2 wk period.
- Adult: 15 mg/kg as a single dose daily. Max: 1 g daily. As part of intermittent regimen: 25-30 mg/kg 2-3 times wkly. Max: 1.5 g/dose.
- Child: 20-40 mg/kg as a single dose daily. Max: 1 g daily. As part of intermittent regimen: 25-30 mg/kg 2-3 times wkly. Max: 1.5 g/dose.
- Elderly: >40 yr Max: 500-750 mg daily.
- Adult: 2 g daily in 2 divided doses for a minimum of 10 days.
- Child: 30 mg/kg daily in 2-3 divided doses. Max: 2 g daily.
- Adult: For concomitant use with other agents and as 2nd line agent: 1-2 g daily in divided doses 6-12 hrly. Max: 2 g daily.
- Child: 20-40 mg/kg daily in divided doses 6-12 hrly.
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Interaction
Additive neurotoxic and nephrotoxic effect with neomycin, kanamycin, gentamicin, cefaloridine, paronomycin, viomycin, polymyxin B, colistin, tobramycin, and ciclosporin. Enhanced ototoxic and nephrotoxic effect with ethacrynic acid, mannitol, furosemide and possibly other diuretics. May enhance the resp depressant effect of neuromuscular blockers. Increased risk of nephrotoxicity with cephalosporins. Reduced excretion with NSAIDs.
Contraindications
Hypersensitivity to streptomycin and other aminoglycosides.
Side Effects
Neurotoxic reactions (e.g. vestibular and cochlear function disturbance, optic nerve dysfunction, peripheral neuritis, arachnoiditis, encephalopathy); paraesthesia of face, rash, fever, angioneurotic oedema, eosinophilia; exfoliative dermatitis, azotemia, leucopenia, thrombocytopenia, pancytopenia, haemolytic anaemia, muscular weakness, amblyopia.
Pregnancy & Lactation
Streptomycin can cause fetal harm when administered to a pregnant woman. Because streptomycin readily crosses the placental barrier, caution in use of the drug is important to prevent ototoxicity in the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Precautions & Warnings
Patient with neuromuscular disorders (e.g. myasthenia gravis), pre-existing vertigo, or hearing loss. Renal impairment. Elderly, childn. Pregnancy and lactation.
Use in Special Populations
Renal Impairment: Dosage adjustment needed.
Therapeutic Class
Aminoglycosides, Anti-Tubercular Antibiotics
Reconstitution
Add 4.2 mL, 3.2 mL, or 1.8 mL of sterile water for inj to prepare a soln containing approx 200 mg, 250 mg, or 400 mg, respectively, of streptomycin per mL.
Storage Conditions
Store between 15-30°C. Protect from light.