What is the recommended streptomycin dose for treating tuberculosis in adults and children, and how should it be adjusted in patients with impaired renal function?

Streptomycin Dosing in Tuberculosis

Standard Adult Dosing

For adults ≤59 years with tuberculosis, administer streptomycin 15 mg/kg daily (maximum 1 g) intramuscularly for the first 2-4 months, then reduce frequency to 2-3 times weekly while maintaining the same mg/kg dose. 1, 2

Initial Intensive Phase

• Give 15 mg/kg daily (maximum 1 g) by intramuscular injection for 5-7 days per week during the first 2-4 months 1, 2
• Intravenous administration is acceptable only when the specific preparation is approved for IV use 2
• The maximum dose may be increased above 1 g in very muscular adults when clinically required 2

Continuation Phase

• After 2-4 months or following culture conversion, reduce to 15 mg/kg three times weekly (or 25 mg/kg three times weekly as an alternative) 1, 2
• Maintain the mg/kg dose at 12-15 mg/kg per administration even when reducing frequency—smaller doses reduce efficacy 1

Pediatric Dosing

Children should receive 15-20 mg/kg daily (maximum 1 g), with the option to switch to three times weekly after the initial period. 1, 2

• The CDC recommends 20-40 mg/kg daily (maximum 1 g) as an alternative regimen 1
• After the initial intensive phase, reduce to 25-30 mg/kg twice weekly 1

Age-Related Dose Reduction

For patients >59 years, reduce the dose to 10 mg/kg daily (maximum 750 mg) to minimize ototoxicity and nephrotoxicity risk. 1, 2

• This age-based reduction reflects decreased renal clearance and substantially higher risk of eighth nerve toxicity 2
• After the initial period, continue at 10 mg/kg but reduce frequency to three times weekly 2

Renal Impairment Adjustments

In renal insufficiency, never reduce the mg/kg dose—instead maintain 12-15 mg/kg per dose but extend the dosing interval to 2-3 times weekly. 1, 2

Specific Renal Dosing Strategy

• For creatinine clearance <30 mL/min or hemodialysis patients: give 12-15 mg/kg 2-3 times weekly 2
• Administer the dose after dialysis to facilitate directly observed therapy and prevent premature drug removal 1, 2
• Therapeutic drug monitoring is mandatory—target trough <5 mg/L (ideally <10 µg/mL) and peak 25-35 mg/L 2
• Consult a pharmacist for all renal dosing adjustments 2

The rationale for maintaining the mg/kg dose while reducing frequency is to preserve the concentration-dependent bactericidal effect of aminoglycosides 1. Smaller doses compromise efficacy even when given more frequently 1.

Obesity Adjustments

For markedly obese patients, calculate the dose using ideal body weight plus 40% of excess weight. 2

• This adjustment accounts for reduced distribution of aminoglycosides into adipose tissue 2
• Do not dose on actual body weight, as this leads to excessive toxicity 2

Therapeutic Drug Monitoring

Obtain peak levels in the first week and trough levels weekly for 4 weeks, then every 2 weeks for the next 4 weeks, and monthly thereafter if stable. 2

Target Concentrations

• Peak: 25-35 mg/L (drawn 60 minutes after infusion ends) 2
• Trough: <5 mg/L (drawn immediately before next dose) 2

When TDM is Essential

• All patients with renal impairment 1, 2
• Elderly patients (>59 years) 2
• Patients on hemodialysis 2
• Poor clinical response 2

Safety Monitoring Requirements

Ototoxicity Surveillance

• Perform baseline audiometry and vestibular testing before starting therapy 1, 2
• Conduct monthly audiometry throughout treatment 2
• Obtain final audiometry 2 months after the last dose 2
• Ototoxicity is defined as ≥20 dB loss at any single frequency or ≥10 dB loss at two adjacent frequencies 2
• Risk increases dramatically with cumulative doses >100-120 g, age >59 years, and concurrent loop diuretics (furosemide, ethacrynic acid) 1, 2

Nephrotoxicity Monitoring

• Check renal function twice weekly in month 1, weekly in month 2, then every 2 weeks until therapy ends 2
• Nephrotoxicity requiring discontinuation occurs in approximately 2% of patients 1
• Streptomycin causes less nephrotoxicity than amikacin, kanamycin, or capreomycin 1

Baseline Assessment

• Audiogram, vestibular testing, Romberg testing, and serum creatinine measurement 1
• Monthly questioning regarding auditory or vestibular symptoms 1

Absolute Contraindications

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

• This contraindication applies throughout all trimesters 1
• Alternative regimens without streptomycin should be used in pregnant patients 3

Drug Interactions Increasing Toxicity

Avoid concurrent use with loop diuretics (furosemide, ethacrynic acid), which markedly increase ototoxicity risk. 1, 2

• Nephrotoxicity risk increases when combined with capreomycin, cephalosporins, cyclosporine, colistimethate sodium, or tacrolimus 2
• Neuromuscular blockade can be potentiated by muscle relaxants, causing postoperative respiratory weakness 1
• Hypocalcemia may occur with concurrent bisphosphonates 2

Critical Pitfalls to Avoid

• Do not reduce the mg/kg dose in renal impairment—only extend the dosing interval to preserve concentration-dependent killing 1, 2
• Do not continue daily dosing beyond 2-4 months when three-times-weekly dosing is appropriate—cumulative toxicity increases markedly after 100-120 g total dose 1
• Do not use standard adult doses in elderly patients without age-based reduction to 10 mg/kg—ototoxicity risk rises substantially 1, 2
• Do not dose obese patients on actual body weight—use the adjusted body-weight formula (IBW + 40% excess) to prevent toxicity 2
• Do not omit therapeutic drug monitoring in renal impairment—serum concentrations are essential to balance efficacy and toxicity 1, 2

Limited CNS Penetration

• Streptomycin has only slight diffusion into CSF, even in patients with meningitis 1
• For tuberculous meningitis, children should receive a minimum of 12 months of therapy with alternative agents that penetrate the CNS 4

Role in MDR-TB Regimens

In multidrug-resistant tuberculosis, streptomycin is a Group 4 agent used when the isolate has demonstrated or presumed susceptibility. 1

• Most streptomycin-resistant strains remain susceptible to amikacin and kanamycin, but there is nearly complete cross-resistance between amikacin and kanamycin 1
• Among patients who acquired M. tuberculosis in high-incidence countries, the relatively high rate of resistance to streptomycin limits its usefulness 1
• For MDR-TB, the dose is 15 mg/kg daily initially, then 25 mg/kg three times weekly after the initial phase 1