Streptomycin

Streptomycin is the first aminoglycoside, given by intramuscular injection. It remains in use for retreatment and drug-resistant tuberculosis, brucellosis, plague, tularaemia and enterococcal endocarditis with high-level gentamicin resistance. Vestibular toxicity is its characteristic adverse effect.

Classification. Aminoglycoside.

Mechanism. Binds the 30S ribosomal subunit; bactericidal.

Spectrum. Mycobacterium tuberculosis (susceptible strains), Brucella, Yersinia pestis, Francisella tularensis, some enterococci (synergy when gentamicin resistance is high-level), and some Gram-negative bacilli. Resistance is common in Enterobacterales.

Pharmacokinetics. IM (poor oral absorption). Peak 1 to 2 hours after injection. Half-life 2 to 3 hours. Eliminated by glomerular filtration. Poor CSF penetration.

Dose by ideal body weight. Maximum 1 g daily in most regimens.

Adults. - Tuberculosis (retreatment or drug-resistant, reserve use): 15 mg/kg IM once daily, maximum 1 g; for those over 59 years or under 50 kg, 10 mg/kg (maximum 750 mg). Intermittent three times weekly: 25 to 30 mg/kg (maximum 1.5 g).

Newer all-oral regimens have largely replaced injectable agents. - Brucellosis: 1 g IM once daily for 14 to 21 days with doxycycline 100 mg every 12 hours for 6 weeks. - Plague: 1 g IM every 12 hours (or 15 mg/kg every 12 hours) for 7 to 10 days. - Tularaemia: 1 g IM every 12 hours (or 15 mg/kg every 12 hours) for 10 days. - Enterococcal endocarditis with high-level gentamicin resistance: 7.5 mg/kg IM or IV every 12 hours with a cell wall agent for 4 to 6 weeks.

Children. Tuberculosis 20 to 40 mg/kg IM once daily (maximum 1 g); plague 30 mg/kg/day in 2 divided doses (maximum 2 g daily). Avoid in neonates.

Alternatives. Gentamicin, amikacin, doxycycline, ciprofloxacin.

Contraindications. Myasthenia gravis; known mitochondrial 12S rRNA mutation (m.1555A>G); previous hypersensitivity; pregnancy (congenital deafness).

Adverse effects. Vestibular toxicity (vertigo, ataxia, nystagmus, oscillopsia), hearing loss, perioral paraesthesia, nephrotoxicity (less than gentamicin), neuromuscular blockade, injection-site pain, hypersensitivity (rash, fever, eosinophilia).

Interactions. Loop diuretics, vancomycin, amphotericin B, ciclosporin, cisplatin and contrast agents; neuromuscular blockers; other ototoxic drugs.

Common prescribing errors. Giving full doses in renal failure or in older and low-weight patients, no monthly audiometry or balance review, and using it in pregnancy.

Special groups.

• Pregnancy: contraindicated. Breastfeeding: compatible (poor oral absorption).
• Older adults: use 10 mg/kg (maximum 750 mg) and monitor closely.
• Kidney impairment: avoid where possible; if used, creatinine clearance 10 to 50 mL/min 7.5 mg/kg every 24 to 72 hours; under 10 mL/min every 72 to 96 hours, set by levels. Haemodialysis: 12 to 15 mg/kg after the session, three times weekly in tuberculosis.
• Liver impairment: no adjustment.
• Region: variable availability in East Africa; used where oral options are not available or in brucellosis and plague.

Preparation. Reconstitute the powder as the label directs (commonly 1 g in 3 to 4 mL water for injection) and give by deep IM injection, rotating sites. Do not use IV except where specifically stated.

Baseline and monitoring. - Baseline: creatinine, audiometry, vestibular examination (Romberg), weight, medication review, pregnancy status. - Levels: peak 1 hour after IM dose 35 to 45 mg/L (daily dosing 20 to 35 mg/L) and trough under 5 mg/L. - Creatinine and electrolytes weekly; audiometry and balance review monthly during tuberculosis treatment.

Stop rules. Stop for vertigo, new hearing loss, creatinine rising by 0.3 mg/dL (26 micromol/L) or more, or neuromuscular weakness.

Referral and escalation. Specialist tuberculosis or infectious diseases input for all uses; ENT or audiology for hearing or vestibular symptoms.