Injectable Anti-Tuberculosis Regimen

Primary Injectable Agents and Their Roles

The Centers for Disease Control and Prevention recommends injectable anti-tuberculosis agents, such as streptomycin, amikacin, kanamycin, and capreomycin, as second-line drugs for drug-resistant tuberculosis, with dosing at 15 mg/kg daily (maximum 1 g) initially, then reduced to 2-3 times weekly after 2-4 months or culture conversion 1, 2
Streptomycin is the first-line injectable option when added to standard regimens for suspected or proven drug resistance, with adult dosing at 15 mg/kg daily (maximum 1 g) intramuscularly or intravenously, given 5-7 days per week initially 3, 4, 1, 2
Amikacin and kanamycin are second-line injectable agents used for drug-resistant tuberculosis with demonstrated or presumed susceptibility, with complete cross-resistance existing between these two drugs, but most streptomycin-resistant strains remain susceptible 1, 2

Injectable agents are typically given daily (5-7 days per week) for the first 2-4 months, with frequency reduced to 2-3 times weekly after culture conversion, depending on efficacy of other drugs in the regimen 1, 2
When transitioning to intermittent dosing, maintain the 12-15 mg/kg per dose to take advantage of concentration-dependent bactericidal effect 1, 2, 6

Critical dosing adjustments are required for patients with renal insufficiency due to almost exclusive renal clearance, with reduced dosing frequency to 2-3 times weekly, but maintaining the 12-15 mg/kg per dose 1, 2, 6
Automatic dose reduction to 10 mg/kg daily (750 mg maximum) is recommended for all patients over 59 years of age, with increased risk of nephrotoxicity and ototoxicity requiring heightened vigilance 1, 2, 6
All injectable agents are contraindicated in pregnancy due to risk of fetal nephrotoxicity and congenital hearing loss 1, 2, 6

Baseline assessment requires audiogram, vestibular testing, and Romberg testing, as well as serum creatinine measurement, with monthly renal function assessment and questioning regarding auditory or vestibular symptoms 1, 2
Repeat audiogram and vestibular testing are recommended if symptoms of eighth nerve toxicity develop, with serum concentration measurements obtained routinely for amikacin, targeting trough level <5 mg/L and peak level 25-35 mg/L for daily dosing or 65-80 mg/L for thrice-weekly dosing 1, 2, 6, 8

Streptomycin primarily causes vestibular dysfunction more than hearing loss, while amikacin and kanamycin cause deafness but less vestibular dysfunction than streptomycin, with high-frequency hearing loss occurring in 24% of patients receiving amikacin 1, 2
Capreomycin causes vestibular disturbances, tinnitus, and deafness, especially in elderly or renally impaired patients, with streptomycin having the lowest nephrotoxicity risk among injectable agents, and amikacin and kanamycin being more nephrotoxic than streptomycin 1, 2, 6

Injectable agents are not part of first-line therapy for drug-susceptible tuberculosis, with the standard regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of isoniazid and rifampin, and streptomycin may be added to the initial regimen when drug resistance is suspected or proven 3, 4
Injectable agents become essential components when treating multidrug-resistant tuberculosis (MDR-TB), with selection based on drug susceptibility testing results, and total cumulative dose not exceeding 120 g over the entire course of therapy unless no other therapeutic options exist 1, 2