What streptomycin dose should be used in a patient on an alternative tuberculosis regimen for drug‑induced liver injury, including weight‑based dosing, maximum dose, frequency, and adjustments for renal impairment?

Streptomycin Dosing for Alternative TB Regimen in DILI

For adults with drug-induced liver injury requiring an alternative TB regimen, streptomycin should be dosed at 15 mg/kg daily (maximum 1 g/day) via intramuscular or intravenous route, with dose reduction to 10 mg/kg daily (maximum 750 mg) for patients over 59 years of age. 1

Weight-Based Dosing

Adults

• Standard dose: 15 mg/kg daily as a single dose, 5-7 days per week initially 1
• Maximum daily dose: 1 g/day 1
• Elderly patients (>59 years): Reduce to 10 mg/kg daily (maximum 750 mg) 1
• Alternative intermittent dosing: Some clinicians prefer 25 mg/kg three times weekly after the initial intensive phase 1

Children

• Daily dosing: 15-20 mg/kg daily (maximum 1 g/day) 1
• Twice weekly dosing: 25-30 mg/kg twice weekly 1
• Maximum dose: 1 g/day 1

Frequency Adjustments

After the first 2-4 months or after culture conversion, the frequency can be reduced to 2-3 times per week while maintaining the 12-15 mg/kg per dose to preserve the concentration-dependent bactericidal effect 1. This reduction depends on the efficacy of other drugs in the regimen 1.

Renal Impairment Adjustments

Critical adjustment principle: Patients with decreased renal function require the 15 mg/kg dose to be given only 2-3 times per week to allow for drug clearance, rather than reducing the individual dose 1. This approach maintains therapeutic peak concentrations while preventing accumulation 1.

• Dosing frequency reduction: 12-15 mg/kg per dose, 2-3 times per week 1
• Rationale: Streptomycin clearance is almost exclusively renal, making dosing adjustments essential to avoid both ototoxicity and nephrotoxicity 1
• Hemodialysis patients: Administer after dialysis to facilitate directly observed therapy and avoid premature drug removal 1
• Monitoring: Serum drug concentrations should be monitored to avoid toxicity in renal impairment 1

Route of Administration

Both intramuscular and intravenous routes are acceptable 1. The intravenous route may be preferred for patients who cannot tolerate painful intramuscular injections 2, 3. Pharmacokinetic parameters are comparable between routes, though intramuscular absorption may show more variability 4.

Special Considerations for DILI Context

Streptomycin is particularly valuable in DILI because it is not hepatotoxic, unlike isoniazid, rifampin, and pyrazinamide 5. This makes it an important alternative when hepatotoxic first-line agents must be avoided 5.

Key Safety Monitoring

• Ototoxicity risk: Increases with cumulative doses above 100-120 g, age >59 years, and concomitant loop diuretics 1
• Nephrotoxicity: Occurs in approximately 2% of patients, less common than with amikacin or capreomycin 1
• Renal function monitoring: Essential throughout treatment due to exclusive renal clearance 1

Common Pitfalls to Avoid

• Do not reduce individual dose size in renal impairment—instead reduce frequency to maintain peak concentrations 1
• Do not use in pregnancy—contraindicated due to risk of fetal hearing loss 1
• Do not rely on streptomycin for CNS penetration—only slight CSF diffusion occurs even with meningitis 1