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Drug Reference

streptomycin

Aminoglycoside antibiotic· Brands: StreptomycinIM

Mechanism of action
Streptomycin is a bactericidal aminoglycoside that binds irreversibly to the 30S ribosomal subunit, interfering with the initiation complex of protein synthesis and causing misreading of mRNA. This leads to disruption of bacterial cell membrane integrity and cell death. It is active against many Gram-negative aerobic bacilli, including Brucella, Francisella, Yersinia, and Mycobacterium tuberculosis, but has no activity against anaerobes, fungi, or viruses. Resistance occurs via plasmid-mediated aminoglycoside-modifying enzymes or ribosomal mutations, and cross-resistance with other aminoglycosides is common.
Pharmacokinetics
Streptomycin is not absorbed from the gastrointestinal tract and must be given parenterally, usually by intramuscular injection. Peak serum concentrations occur 30 to 60 minutes after IM administration. It is minimally protein-bound and distributes mainly into extracellular fluid, with poor penetration into cerebrospinal fluid, aqueous humour, and bone. It crosses the placenta and is excreted in breast milk. The drug is not metabolised and is eliminated unchanged by glomerular filtration. The elimination half-life is approximately 2 to 5 hours in normal renal function but is markedly prolonged in renal impairment. Dose adjustment and therapeutic drug monitoring are required in renal insufficiency.
Indications & dosing

Tuberculosis (second-line agent, in combination regimens)

Use with other antituberculous drugs. Monitor for ototoxicity and nephrotoxicity. Adjust in renal impairment and low body weight.

  • adult · IM: 1000 mg once daily · Use with other antituberculous drugs. Monitor for ototoxicity and nephrotoxicity. Adjust in renal impairment and low body weight.

Plague (Yersinia pestis)

First-line treatment. Duration 10 days or until 3 days after fever resolves. Alternatives include gentamicin and doxycycline.

  • adult · IM: 1000 mg every 12 hours · First-line treatment. Duration 10 days or until 3 days after fever resolves. Alternatives include gentamicin and doxycycline.

Tularemia (Francisella tularensis)

First-line treatment. Duration 10 to 21 days depending on severity. Monitor renal function and hearing.

  • adult · IM: 1000 mg every 12 hours · First-line treatment. Duration 10 to 21 days depending on severity. Monitor renal function and hearing.

Brucellosis (in combination with doxycycline)

Combine with doxycycline for 2 to 3 weeks. WHO regimen. Avoid monotherapy to prevent resistance.

  • adult · IM: 1000 mg once daily · Combine with doxycycline for 2 to 3 weeks. WHO regimen. Avoid monotherapy to prevent resistance.
Contraindications & precautions
  • Known hypersensitivity to streptomycin or another aminoglycoside · Cross-sensitivity within the aminoglycoside class occurs. Previous anaphylaxis or severe reaction is an absolute bar to further exposure.
  • Pre-existing vestibular or cochlear damage, or other eighth cranial nerve impairment · Streptomycin concentrates in the inner ear and can cause further irreversible vestibular and auditory damage.
  • Myasthenia gravis · Aminoglycosides impair neuromuscular transmission and may precipitate marked weakness or respiratory failure. Use only if no alternative exists, with respiratory monitoring.
  • Pregnancy · Risk of fetal eighth nerve and renal toxicity. Reserve for serious indications such as tularaemia or plague where benefit outweighs risk, and follow local guidance.
  • Severe renal impairment · Reduced clearance causes accumulation and increases nephrotoxicity and ototoxicity. Requires dose reduction and close monitoring, or an alternative agent.
  • Concurrent or recent ototoxic or nephrotoxic therapy · Additive damage with other aminoglycosides, loop diuretics, vancomycin, amphotericin B or cisplatin. Avoid unless the combination is unavoidable.
  • Obtain baseline renal function, audiometry and vestibular assessment, then repeat periodically. Ask directly about tinnitus, hearing loss, vertigo and unsteadiness at each review and stop treatment if they appear.
  • Dose by body weight and renal function. Where assays are available, measure peak and trough serum concentrations and adjust the dose to the local target range.
  • Give by deep intramuscular injection or slow intravenous infusion over 30 to 60 minutes. Avoid rapid intravenous injection and ensure adequate hydration.
  • Avoid concomitant ototoxic or nephrotoxic drugs such as loop diuretics, vancomycin, amphotericin B, cisplatin and other aminoglycosides.
  • Use with caution in myasthenia gravis and Parkinson's disease, and avoid concurrent neuromuscular blocking agents; calcium salts may be used to reverse blockade.
  • In tuberculosis, use only within a recommended combination regimen and never as monotherapy. Availability and use vary by region; many national programmes have replaced streptomycin with other injectable agents. Verify against local formulary and resistance data.
Adverse effects
  • Vestibular toxicity: vertigo, ataxia, nystagmus, unsteadinessserious
  • Cochlear toxicity: hearing loss, tinnitusserious
  • Nephrotoxicity: rising serum creatinine, tubular damage, electrolyte lossserious
  • Neuromuscular blockade with muscle weakness and respiratory depressionserious
  • Anaphylaxis and severe hypersensitivity reactionsserious
  • Optic nerve dysfunction with scotoma or visual disturbanceserious
  • Circumoral and perioral paraesthesia, numbness, tingling of the face
  • Injection site pain, induration and sterile abscess
  • Rash, drug fever, eosinophilia
  • Blood dyscrasias: anaemia, leucopenia, thrombocytopenia
Renal & hepatic adjustment
  • eGFR 60+: No specific renal dose adjustment. Use standard weight-based dose and monitor serum concentrations and renal function.
  • eGFR 30–59.9: Reduce dose or extend the dosing interval (for example, from 24 to 48 hours) and monitor serum streptomycin concentrations closely. Seek specialist advice.
  • eGFR 15–29.9: Avoid if a safer alternative exists. If essential, use a reduced dose at extended intervals (for example, every 48 to 72 hours or longer) under specialist supervision with therapeutic drug monitoring. (avoid)
  • eGFR 0–14.9: Avoid. If no alternative, specialist dosing is required with therapeutic drug monitoring; give after haemodialysis on dialysis days. (avoid)
Monitoring, pregnancy & toxicity
  • Renal function (serum creatinine, eGFR, urinalysis for protein, casts, haematuria) · Baseline then at least weekly, and more often if renal impairment or concomitant nephrotoxins
  • Serum streptomycin peak and trough concentrations · As per local protocol, especially in renal impairment, obesity, or prolonged therapy
  • Audiometry and vestibular function · Baseline and periodically during therapy; urgently if tinnitus, hearing loss, vertigo or ataxia
  • Serum electrolytes (potassium, magnesium, calcium) · Baseline and periodically; more often if renal impairment or diuretics
  • Neuromuscular function and respiratory status · Monitor in patients with myasthenia gravis or receiving neuromuscular blockers; observe after intraperitoneal or high-dose IV use
  • Pregnancy: Avoid streptomycin in pregnancy unless there is no safer alternative and the infection is life-threatening. It crosses the placenta and can cause irreversible fetal ototoxicity (congenital deafness) and vestibular damage. If use is unavoidable, involve specialist perinatal and infectious diseases teams, document informed consent, and arrange audiological monitoring after birth.
  • Toxicity: Ototoxicity: cochlear (tinnitus, high-frequency hearing loss, deafness) and vestibular (vertigo, nystagmus, ataxia, nausea). May be irreversible. · Stop streptomycin immediately. Obtain urgent audiometry and vestibular assessment. Provide supportive care and vestibular rehabilitation; hearing aids or cochlear implant assessment for permanent loss. No specific antidote.
  • Toxicity: Nephrotoxicity: rising serum creatinine, non-oliguric renal failure, proteinuria, cylindruria, electrolyte wasting. · Stop the drug, maintain hydration, monitor renal function and electrolytes, adjust other nephrotoxins, and consider dialysis in severe renal failure or overdose. Streptomycin is removed by haemodialysis.
  • Toxicity: Neuromuscular blockade: muscle weakness, hyporeflexia, respiratory depression, apnoea, especially with myasthenia gravis, anaesthesia or intraperitoneal administration. · Support ventilation and oxygenation. Calcium gluconate may partially reverse blockade; avoid concomitant neuromuscular blockers. Stop streptomycin.
  • Toxicity: Hypersensitivity and injection-site reactions: rash, fever, eosinophilia, urticaria, pain or abscess at IM site. Circumoral paraesthesia after injection is usually transient. · Stop drug for significant hypersensitivity; give antihistamines or corticosteroids as appropriate; manage injection site with analgesia and aseptic technique. Reassure for transient circumoral paraesthesia if no other symptoms.
Clinical notes
Streptomycin is reserved for specific indications owing to its toxicity. It is a second-line agent for tuberculosis, used in combination regimens when resistance or intolerance to first-line drugs occurs. It is a first-line treatment for plague, tularaemia, and brucellosis (usually with doxycycline). It is also used with penicillin for enterococcal endocarditis. Dosing is by weight (e.g., 15 mg/kg IM daily for tuberculosis, up to 1 g; 1 g IM twice daily for plague) but varies by indication and local guidelines. Major adverse effects are vestibular and cochlear ototoxicity, nephrotoxicity, and neuromuscular blockade. Baseline and periodic audiometry, renal function tests, and serum drug levels are advised. Streptomycin is contraindicated in myasthenia gravis and during pregnancy unless the benefit outweighs the risk.

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BNF; WHO Model Formulary; local antimicrobial guidelines