Is streptomycin (an aminoglycoside antibiotic) effective for treating tuberculosis meningitis (TBM)?

Streptomycin for Tuberculosis Meningitis (TBM)

Streptomycin is not recommended as a first-line agent for tuberculosis meningitis due to its poor penetration into the cerebrospinal fluid, but may be considered as a fourth drug option in the initial phase of treatment when the meninges are inflamed. 1

CSF Penetration and Efficacy

Streptomycin has poor cerebrospinal fluid (CSF) penetration, which significantly limits its effectiveness in treating tuberculosis meningitis. This pharmacokinetic limitation makes it a suboptimal choice for CNS tuberculosis compared to other available agents 2.

The CSF penetration hierarchy of anti-TB medications is:

• Good penetration: Isoniazid, pyrazinamide, ethionamide
• Moderate penetration: Rifampicin, fluoroquinolones
• Poor penetration: Streptomycin, other aminoglycosides, ethambutol

Recommended Treatment Approach for TBM

Initial Phase (First 2 Months)

• First-line agents: Rifampicin, isoniazid, and pyrazinamide
• Fourth drug options (choose one):
  • Ethambutol (preferred over streptomycin despite also having poor CSF penetration)
  • Streptomycin (only if ethambutol cannot be used)
  • Fluoroquinolone (particularly levofloxacin or moxifloxacin) - better CSF penetration than either ethambutol or streptomycin 1

Continuation Phase (Months 3-12)

• Rifampicin and isoniazid for a total treatment duration of 12 months 1

Important Considerations with Streptomycin

If streptomycin must be used, consider these critical factors:

1. Dosing:

   • Adults: 15 mg/kg/day (maximum 1g/day) parenterally as a single daily dose
   • Elderly (>59 years): Reduced to 10 mg/kg/day (maximum 750 mg)
   • Children: 15-20 mg/kg/day (range 12-18 mg/kg) 3, 2

2. Administration: Given parenterally (IM or IV) 3

3. Major adverse effects:

   • Ototoxicity (vestibular and hearing disturbances) - most significant concern
   • Nephrotoxicity (less common than with other aminoglycosides)
   • Neurotoxicity (circumoral paresthesias) 3

4. Contraindications:

   • Pregnancy (risk of fetal hearing loss)
   • Severe renal impairment (requires significant dose adjustment) 3

5. Monitoring requirements:

   • Baseline and periodic audiometry
   • Renal function tests
   • Therapeutic drug monitoring when available 3

Drug Resistance Considerations

Isoniazid and/or streptomycin resistance has been associated with slower CSF bacterial clearance but does not significantly affect clinical outcomes when patients are treated with appropriate regimens 4. However, combined isoniazid and rifampicin resistance is strongly predictive of death (relative risk 11.63) 4.

Alternative Approaches

For patients who cannot tolerate streptomycin or in settings with high drug resistance:

• Levofloxacin is recommended for isoniazid-resistant TB (6 months of rifampicin, ethambutol, pyrazinamide, and levofloxacin) 1
• Ethionamide has excellent CSF penetration with concentrations equal to those in serum 1
• High-dose rifampicin combined with levofloxacin has been investigated to improve outcomes in TBM 5

Adjunctive Therapy

Corticosteroids are recommended for moderate to severe TBM (stages II and III):

• Dexamethasone 6-12 mg/day or prednisone 60-80 mg/day initially
• Taper over 4-8 weeks
• Has been shown to improve mortality in TBM 1, 6

In summary, while streptomycin was historically important in TB treatment (including the landmark Medical Research Council trials of 1948 3), its poor CSF penetration makes it a suboptimal choice for TBM. Modern treatment approaches favor other agents with better CNS penetration when possible.