Is streptomycin 750 mg intramuscularly administered three times weekly an appropriate regimen for tuberculosis treatment?

Streptomycin 750 mg IM Three Times Weekly for Tuberculosis

Streptomycin 750 mg intramuscularly three times weekly is an appropriate regimen for tuberculosis treatment only in patients over 59 years of age or those with renal impairment after an initial intensive phase of daily dosing. 1

Standard Adult Dosing (≤59 Years)

For adults 59 years or younger with normal renal function, the recommended approach is:

• Initial intensive phase: 15 mg/kg daily (maximum 1 g/day) IM for the first 2–4 months or until culture conversion 1
• Continuation phase: After the initial period, reduce frequency to 12–15 mg/kg per dose (not 750 mg) given two or three times weekly 1

The 750 mg dose is too low for standard adult patients under 60 years, as it fails to achieve the concentration-dependent bactericidal effect required for efficacy. 1 The guidelines explicitly state that smaller doses may reduce drug efficacy, and the milligram dose should be maintained at 12–15 mg/kg per administration even when frequency is reduced. 1

Age-Specific Dosing (>59 Years)

For patients over 59 years of age, 750 mg (10 mg/kg) is the correct dose due to age-related decline in renal clearance and substantially increased risk of ototoxicity. 1, 2

• Initial phase: 10 mg/kg daily (maximum 750 mg) for 2–4 months 1, 2
• Continuation phase: Same 750 mg dose given three times weekly 1, 2

This age-based reduction is critical because ototoxicity risk increases markedly with age, particularly when cumulative doses exceed 100–120 g. 1, 2

Renal Impairment Dosing

In patients with renal insufficiency (creatinine clearance <30 mL/min) or on hemodialysis, the regimen should be:

• Maintain the dose at 12–15 mg/kg per administration (which may be 750 mg in a 50–60 kg patient) 1, 2
• Reduce frequency to 2–3 times weekly 1, 2
• Administer after dialysis to prevent premature drug removal 1, 2
• Monitor serum drug concentrations to balance efficacy and toxicity 1, 2

The critical principle is that the mg/kg dose must not be reduced in renal impairment because streptomycin's bactericidal activity is concentration-dependent; only the dosing interval should be extended. 1, 2

Common Pitfalls to Avoid

• Do not use 750 mg three times weekly as initial therapy in adults ≤59 years with normal renal function—this underdoses the patient and compromises treatment efficacy 1, 2
• Do not continue daily dosing beyond 2–4 months when intermittent dosing is appropriate, as cumulative toxicity rises sharply after 100–120 g total dose 1, 2
• Do not reduce the mg/kg dose in renal impairment—only extend the dosing interval to preserve bactericidal activity 1, 2
• Do not use standard adult doses in elderly patients without age-based reduction to 10 mg/kg (750 mg), as ototoxicity risk increases substantially 1, 2

Safety Monitoring Requirements

Ototoxicity Surveillance

• Baseline audiometry and vestibular testing before starting therapy 1, 2
• Monthly audiometry throughout treatment 2
• Final audiometry 2 months after last dose 2
• Ototoxicity is defined as ≥20 dB loss at any single frequency or ≥10 dB loss at two adjacent frequencies 2
• Risk factors include age >59 years, cumulative dose >100–120 g, and concurrent loop diuretics (furosemide, ethacrynic acid) 1, 2

Nephrotoxicity Monitoring

• Baseline serum creatinine and Romberg testing 1
• Month 1: Check renal function twice weekly 2
• Month 2: Check weekly 2
• Month 3 onward: Check every 2 weeks until aminoglycoside therapy ends 2
• Nephrotoxicity requiring discontinuation occurs in approximately 2% of patients, less frequently than with amikacin or kanamycin 1, 2

Absolute Contraindications

Streptomycin is absolutely contraindicated in pregnancy throughout all trimesters due to risk of fetal hearing loss. 1, 2

Drug Interactions Increasing Toxicity

• Loop diuretics (furosemide, ethacrynic acid) markedly increase ototoxicity risk and should be avoided 1, 2
• Muscle relaxants can potentiate neuromuscular blockade, leading to postoperative respiratory weakness 1, 2
• Nephrotoxic agents (capreomycin, cephalosporins, cyclosporine, tacrolimus) increase nephrotoxicity risk 2

Clinical Context for 750 mg Three Times Weekly

The 750 mg three times weekly regimen is appropriate only in these specific scenarios:

1. Elderly patients (>59 years) after initial daily dosing phase 1, 2
2. Patients with renal impairment (if body weight is approximately 50–60 kg, making 12–15 mg/kg equal to 750 mg) 1, 2
3. Continuation phase after 2–4 months of daily therapy in age-appropriate or renally impaired patients 1, 2

For standard adults ≤59 years with normal renal function, the three-times-weekly dose should be 12–15 mg/kg (typically 900 mg–1 g in a 60–75 kg patient), not 750 mg. 1, 2