Injectable Anti-Tuberculosis Regimen
Injectable anti-tuberculosis agents are second-line drugs reserved primarily for drug-resistant tuberculosis, with streptomycin, amikacin, kanamycin, and capreomycin being the main options, each dosed at 15 mg/kg daily (maximum 1 g) initially, then reduced to 2-3 times weekly after 2-4 months or culture conversion. 1
Primary Injectable Agents and Their Roles
Streptomycin
- First-line injectable option when added to standard regimens for suspected or proven drug resistance 1
- Adult dosing: 15 mg/kg daily (maximum 1 g) intramuscularly or intravenously, given 5-7 days per week initially 1
- Reduced to 10 mg/kg daily (750 mg maximum) for patients over 59 years of age 1, 2
- Intermittent dosing: 25-30 mg/kg (maximum 1.5 g) when given twice or thrice weekly 2
- Pediatric dosing: 15-20 mg/kg daily, or 25-30 mg/kg for intermittent dosing 1
Amikacin and Kanamycin
- Second-line injectable agents used for drug-resistant tuberculosis with demonstrated or presumed susceptibility 1
- Complete cross-resistance exists between these two drugs, but most streptomycin-resistant strains remain susceptible 1
- Adult dosing: 15 mg/kg daily (maximum 1 g) intramuscularly or intravenously, given 5-7 days per week initially 1
- Reduced to 10 mg/kg daily (750 mg) for patients over 59 years 1
- Pediatric dosing: 15-30 mg/kg daily (maximum 1 g) 1
- Amikacin may be more readily available with easier serum concentration monitoring 1
Capreomycin
- Second-line injectable agent for drug-resistant tuberculosis 1
- Adult dosing: 15 mg/kg daily (maximum 1 g), given 5-7 days per week initially 1
- Reduced to 10 mg/kg daily (750 mg) for patients over 59 years 1
- Pediatric dosing: 15-30 mg/kg daily (maximum 1 g) 1
Treatment Duration and Frequency Adjustments
Initial Intensive Phase
- Injectable agents are typically given daily (5-7 days per week) for the first 2-4 months 1
- Frequency is reduced to 2-3 times weekly after culture conversion, depending on efficacy of other drugs in the regimen 1
Continuation Phase Dosing
- When transitioning to intermittent dosing, maintain the 12-15 mg/kg per dose (not reduced milligram amount) to take advantage of concentration-dependent bactericidal effect 1
- Smaller doses may reduce drug efficacy 1
Special Population Considerations
Renal Insufficiency
- Critical dosing adjustments required due to almost exclusive renal clearance 1
- Reduce dosing frequency to 2-3 times weekly, but maintain the 12-15 mg/kg per dose 1
- For hemodialysis patients, administer after dialysis to facilitate directly observed therapy and avoid premature drug removal 1
- Serum drug concentration monitoring mandatory to avoid toxicity 1
Elderly Patients
- Automatic dose reduction to 10 mg/kg daily (750 mg maximum) for all patients over 59 years of age 1, 2
- Increased risk of nephrotoxicity and ototoxicity requires heightened vigilance 1
Pregnancy
- All injectable agents are contraindicated in pregnancy due to risk of fetal nephrotoxicity and congenital hearing loss 1
Hepatic Disease
- No dose adjustments necessary for streptomycin, amikacin, or kanamycin in hepatic disease 1, 3
- These agents are not hepatotoxic and require no liver function monitoring 3
Monitoring Requirements
Baseline Assessment
- Audiogram, vestibular testing, and Romberg testing required before initiating therapy 1
- Serum creatinine measurement at baseline 1
Ongoing Monitoring
- Monthly renal function assessment and questioning regarding auditory or vestibular symptoms 1
- Repeat audiogram and vestibular testing if symptoms of eighth nerve toxicity develop 1
- For amikacin, serum concentration measurements should be obtained routinely 1, 4
- Target trough level <5 mg/L; target peak level 25-35 mg/L for daily dosing or 65-80 mg/L for thrice-weekly dosing 4
Adverse Effects Profile
Ototoxicity
- Streptomycin primarily causes vestibular dysfunction more than hearing loss 1
- Amikacin and kanamycin cause deafness but less vestibular dysfunction than streptomycin 1
- High-frequency hearing loss occurred in 24% of patients receiving amikacin in one report, with higher rates in those receiving longer treatment or higher doses 1
- Capreomycin causes vestibular disturbances, tinnitus, and deafness, especially in elderly or renally impaired patients 1
Nephrotoxicity
- Streptomycin has the lowest nephrotoxicity risk among injectable agents, with renal insufficiency requiring discontinuation in approximately 2% of patients 1
- Amikacin and kanamycin are more nephrotoxic than streptomycin, with renal impairment in 8.7% of patients receiving amikacin (3.4% in those without risk factors) 1
- Capreomycin has the highest nephrotoxicity risk, requiring discontinuation in 20-25% of patients 1
- Risk factors include initially elevated creatinine, larger total doses, and concurrent nephrotoxic agents 1
Clinical Context and Integration
Role in Standard Regimens
- Injectable agents are not part of first-line therapy for drug-susceptible tuberculosis 1
- The standard regimen for drug-susceptible TB is 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of isoniazid and rifampin 1
- Streptomycin may be added to the initial regimen when drug resistance is suspected or proven 1, 2