How should streptomycin be used in adult tuberculosis patients, including indications, dosage, monitoring, contraindications, and alternative agents?

Streptomycin in Tuberculosis Treatment

Streptomycin is a second-line injectable aminoglycoside reserved for drug-resistant TB or when first-line oral agents cannot be used, administered intramuscularly at 15 mg/kg daily (maximum 1 g) in adults under 60 years, with mandatory dose reduction to 10 mg/kg in elderly patients and contraindicated in pregnancy due to fetal ototoxicity. 1, 2

Current Role and Indications

• Streptomycin is NOT part of the standard first-line regimen for drug-susceptible TB, which consists of rifampin, isoniazid, pyrazinamide, and ethambutol (2HRZE/4HR). 1
• Streptomycin may be added when drug resistance is suspected or proven, particularly in settings where ethambutol cannot be used or when isoniazid resistance is documented. 1, 3
• The fourth drug in initial therapy can be streptomycin instead of ethambutol in children too young to be monitored for visual acuity, though this is now less common practice. 3
• For isoniazid-resistant TB, regimens containing rifampin, pyrazinamide, ethambutol, and streptomycin for 6 months have shown 95% success rates in British Medical Research Council trials. 1

Dosing Regimens

Standard Adult Dosing

• Daily therapy: 15 mg/kg intramuscularly (maximum 1 g daily). 2
• Twice-weekly therapy: 25–30 mg/kg intramuscularly (maximum 1.5 g per dose). 2
• Thrice-weekly therapy: 25–30 mg/kg intramuscularly (maximum 1.5 g per dose). 2

Age-Related Adjustments

• Patients over 60 years: Reduce dose to 10 mg/kg daily (maximum 1 g) due to significantly increased risk of ototoxicity and nephrotoxicity. 2
• For bacterial endocarditis in elderly: Use 500 mg twice daily for the entire treatment course rather than the standard 1 g twice daily. 2

Pediatric Dosing

• Daily: 20–40 mg/kg (maximum 1 g). 2
• Twice-weekly: 25–30 mg/kg (maximum 1.5 g). 2
• Thrice-weekly: 25–30 mg/kg (maximum 1.5 g). 2

Cumulative Dose Limit

• Total cumulative dose should not exceed 120 g over the entire treatment course unless no other therapeutic options exist. 2

Renal Impairment Adjustments

• Streptomycin requires dose reduction in renal insufficiency, unlike rifampin which can be given at standard doses. 1
• Dosing frequency should be reduced to 2–3 times weekly while maintaining the 12–15 mg/kg per-dose amount in patients with renal dysfunction. 4
• Serum drug concentration monitoring is mandatory when streptomycin is used in renal impairment. 1
• Baseline serum creatinine and monthly monitoring are required throughout therapy. 4

Hepatic Disease Considerations

• Streptomycin requires no dose adjustment or special precautions in liver disease because it is eliminated renally rather than hepatically and has no documented hepatotoxic effects. 4
• No liver function monitoring is required when using streptomycin, in contrast to rifampin, isoniazid, and pyrazinamide. 4
• Streptomycin is a safe option for TB patients with chronic liver disease, alcoholism, cirrhosis, or hepatitis B/C infection who require treatment. 4

Administration Technique

• Intramuscular route only—never administer intravenously as a bolus. 2
• Preferred injection sites in adults: Upper outer quadrant of buttock (gluteus maximus) or mid-lateral thigh. 2
• Preferred site in children: Mid-lateral thigh muscles; avoid gluteal region except when necessary (e.g., burn patients) to minimize sciatic nerve injury risk. 2
• Deltoid area: Use only in well-developed adults and older children, with caution to avoid radial nerve injury. 2
• Always aspirate before injection to avoid inadvertent intravascular administration. 2
• Rotate injection sites to prevent local complications. 2

Monitoring Requirements

Ototoxicity Surveillance (Primary Concern)

• Baseline audiogram and vestibular testing before initiating therapy. 4
• Monthly assessment for auditory or vestibular symptoms throughout treatment. 4
• Ototoxicity risk is markedly increased in elderly patients and those using loop diuretics concurrently. 4
• Discontinue streptomycin immediately if vestibular dysfunction or hearing loss develops. 2

Nephrotoxicity Monitoring

• Baseline serum creatinine before starting therapy. 4
• Monthly serum creatinine measurements during treatment. 4
• Nephrotoxicity occurs in approximately 2% of patients, less commonly than with other aminoglycosides. 4

Neurotoxicity Assessment

• Monitor for circumoral paresthesias after injection, which can occur acutely. 4
• Assess for respiratory muscle weakness, particularly in patients receiving muscle relaxants or with neuromuscular disorders. 4

Absolute Contraindications

• Pregnancy: Streptomycin and all aminoglycosides are contraindicated due to risk of irreversible fetal hearing loss and ototoxicity. 1, 4
• Should pregnancy occur during rifampin-containing therapy, it is NOT an indication for termination, but streptomycin must be discontinued immediately. 1

Drug Resistance Considerations

• Streptomycin resistance develops through mutations in the rpsL gene (encoding ribosomal protein S12) or rrs gene (encoding 16S rRNA). 5
• Cross-resistance between streptomycin and kanamycin/amikacin can occur through mutations in the whiB7 regulatory region, leading to increased expression of efflux pumps. 6
• High-level streptomycin resistance arises at higher frequency in strains with whiB7 mutations compared to wild-type strains. 6
• In multidrug-resistant TB (MDR-TB), streptomycin is considered a second-line injectable agent alongside kanamycin, amikacin, and capreomycin. 1

Treatment Duration by Indication

• Drug-susceptible TB with isoniazid resistance: 6 months when streptomycin is part of a rifampin-containing four-drug regimen. 1
• Rifampin-resistant TB: 9–12 months with streptomycin as part of an alternative regimen. 1
• Tularemia: 7–14 days until patient is afebrile for 5–7 days. 2
• Plague: Minimum 10 days at 2 g daily in divided doses. 2
• Streptococcal endocarditis: 2 weeks total (1 g twice daily for week 1, then 500 mg twice daily for week 2). 2
• Enterococcal endocarditis: 6 weeks total (1 g twice daily for 2 weeks, then 500 mg twice daily for 4 weeks). 2

Alternative Agents When Streptomycin Cannot Be Used

• Ethambutol is the preferred alternative fourth drug in the initial phase of drug-susceptible TB treatment. 1
• For drug-resistant TB, alternative injectable agents include kanamycin, amikacin, or capreomycin. 1
• Fluoroquinolones (levofloxacin, moxifloxacin) can strengthen regimens when streptomycin is contraindicated or not tolerated. 1

Special Populations

HIV-Positive Patients

• Standard streptomycin dosing applies to HIV-infected individuals when the drug is indicated. 1
• Mortality is higher in dual TB/HIV infection, requiring close clinical and bacteriologic monitoring. 1

Unconscious Patients

• Streptomycin is given intramuscularly in standard doses when oral medications cannot be administered. 1

Breastfeeding

• Patients can breastfeed normally while taking streptomycin, though this is rarely relevant given pregnancy contraindication. 1

Common Pitfalls to Avoid

• Do not use streptomycin in pregnant women under any circumstances—the risk of fetal ototoxicity is unacceptable. 1, 4
• Do not fail to reduce the dose in elderly patients—standard adult dosing in those over 60 carries excessive toxicity risk. 2
• Do not neglect baseline and monthly audiometry/vestibular testing—ototoxicity may be irreversible if not detected early. 4
• Do not use standard daily doses in renal impairment—adjust to intermittent dosing with therapeutic drug monitoring. 1, 4
• Do not exceed 120 g cumulative dose except when absolutely no alternatives exist. 2
• Do not assume streptomycin is first-line therapy—it is reserved for specific resistance patterns or contraindications to ethambutol. 1, 3