Streptomycin

Active Ingredient & Mechanism of Action

• Active Ingredient: Streptomycin sulfate.
• Mechanism: Streptomycin acts as a rapid bactericidal antibiotic by targeting bacterial protein synthesis:
  1. Ribosomal Binding: It selectively binds to the 30S ribosomal subunit (specifically the 16S rRNA component) of susceptible bacteria.
  2. Inhibition of Translation: This binding interferes with the initiation complex of protein synthesis and causes misreading of the genetic code (mRNA), leading to the insertion of incorrect amino acids into growing polypeptide chains.
  3. Bacterial Membrane Damage: Accumulation of nonfunctional, misfolded proteins damages the bacterial cell membrane, ultimately causing cell death.

Dosage Forms & Available Strengths

• Powder for Injection (Vials): Typically supplied as 1 gram (1,000 mg) sterile powder vials for reconstitution with sterile water or normal saline for intramuscular (IM) injection.

Clinical Indications

• Tuberculosis (TB): Used as a second-line or specialized adjunctive agent in combination regimens for treatment of active Mycobacterium tuberculosis infections, especially in cases of drug resistance or when first-line options cannot be used.
• Zoonotic Bacterial Infections: First-line treatment (often combined with tetracyclines) for severe infections, including:
  • Tularemia (Francisella tularensis)
  • Plague (Yersinia pestis)
  • Brucellosis (Brucella species)
• Bacterial Endocarditis: Used in combination with penicillin or ampicillin for synergistic bactericidal treatment of enterococcal or streptococcal endocarditis.
• Other Severe Infections: Treatment of infections caused by sensitive Gram-negative organisms like Pseudomonas aeruginosa or Escherichia coli when alternative lower-toxicity antibiotics are ineffective.

Key Pharmacokinetics

• Absorption: Negligible oral absorption; must be administered via deep intramuscular injection for systemic distribution.
• Distribution: Distributes widely into extracellular fluids, pleural fluid, and tissues. Poor penetration across the intact blood-brain barrier (does not achieve therapeutic concentrations in cerebrospinal fluid unless meninges are severely inflamed).
• Elimination & Half-Life: Serum half-life is approximately 2 to 3 hours in adults with normal renal function. Excreted almost entirely unchanged by the kidneys via glomerular filtration.

Administration Guidelines

• Route: Administered by deep intramuscular (IM) injection into a large muscle mass (such as the upper outer quadrant of the gluteus muscle or anterolateral thigh). Rotational site protocols are required for ongoing therapy.
• Renal Adjustments: Because it is cleared through the kidneys, dosing frequency and total dose must be strictly reduced in patients with renal impairment or decreased glomerular filtration rates.

Safety Profile & Considerations

• Boxed Warnings (Black Box Warnings):
  1. Ototoxicity: Can cause irreversible damage to the eighth cranial nerve (vestibulocochlear nerve). This manifests as vestibular damage (dizziness, vertigo, ataxia) and auditory loss (tinnitus, high-frequency hearing loss, or permanent deafness).
  2. Nephrotoxicity: Potential for severe renal tubular damage and acute kidney injury. Monitoring of serum creatinine, BUN, and urine output is required.
  3. Neuromuscular Blockade: Can induce respiratory paralysis or muscle weakness, particularly when co-administered with neuromuscular blocking agents or anesthetics, or in patients with myasthenia gravis.
  4. Fetal Harm: Crosses the placenta and can cause congenital total, irreversible bilateral deafness in the fetus if administered during pregnancy.
• Common Side Effects: Injection site pain, numbness/tingling around the mouth (perioral paresthesia), nausea, vomiting, dizziness, and skin rash.
• Contraindications: Severe hypersensitivity to streptomycin or other aminoglycosides; pregnancy.
• Key Interactions:
  • Other Ototoxic/Nephrotoxic Drugs: Concurrent use with loop diuretics (e.g., furosemide), vancomycin, cisplatin, or other aminoglycosides greatly increases the risk of severe hearing loss and kidney failure.
  • Neuromuscular Blockers: May enhance muscle relaxation and prolong respiratory depression.

Note: Streptomycin is a restricted parenteral antibiotic. Dosing calculations, therapeutic drug monitoring (peak and trough blood levels), renal function assessment, and periodic audiometric testing must be managed under direct clinical supervision.