When should streptomycin be used in tuberculous meningitis?

When to Use Streptomycin in Tuberculous Meningitis

Streptomycin should be used as the fourth drug in the initial 2-month intensive phase of tuberculous meningitis treatment when ethambutol cannot be used (particularly in unconscious patients where visual acuity monitoring is impossible) or in geographic areas where streptomycin resistance is uncommon. 1

Primary Indication for Streptomycin

• Streptomycin serves as an alternative fourth drug option in the initial intensive phase of tuberculous meningitis treatment, alongside isoniazid, rifampicin, and pyrazinamide for the first 2 months. 1
• The standard fourth drug choice is ethambutol (15 mg/kg daily), but streptomycin (15 mg/kg daily intramuscularly) can be substituted when ethambutol is contraindicated. 1, 2, 3

Specific Clinical Scenarios Favoring Streptomycin

Unconscious or Obtunded Patients

• Streptomycin is preferred over ethambutol in unconscious patients because ethambutol's primary toxicity is optic neuritis, which cannot be monitored when visual acuity testing is impossible. 2, 4
• In comatose or stuporous patients (Stage III disease), streptomycin avoids the risk of undetected visual complications. 5

Geographic Considerations

• In areas where streptomycin resistance is uncommon, it remains a viable fourth drug option for the initial phase. 1
• However, in geographic regions with high streptomycin resistance (common in many areas), alternative aminoglycosides such as kanamycin, amikacin, or capreomycin should be used instead. 1

Critical Limitations of Streptomycin in CNS Tuberculosis

Poor CNS Penetration

• Streptomycin penetrates the cerebrospinal fluid poorly and only achieves adequate concentrations when meninges are acutely inflamed during the early stages of treatment. 2, 3, 4, 6
• CSF levels of streptomycin only slightly exceed the minimal inhibitory concentration (MIC) against M. tuberculosis, even during active meningeal inflammation. 6
• This limited penetration restricts streptomycin's utility to the initial 2-month phase only, after which it provides no additional benefit. 2, 3, 4

Toxicity Concerns

• Streptomycin is ototoxic and must be avoided in pregnancy due to risk of fetal hearing damage. 1
• In renal impairment, streptomycin requires dose reduction and serum concentration monitoring. 1
• Intrathecal administration of streptomycin is unnecessary and not recommended. 2

Treatment Regimen When Using Streptomycin

• Initial intensive phase (2 months): Isoniazid (5 mg/kg up to 300 mg daily) + Rifampicin (10 mg/kg up to 600 mg daily) + Pyrazinamide (35 mg/kg up to 2 g daily) + Streptomycin (15 mg/kg daily intramuscularly). 1, 2, 3
• Continuation phase (10 months): Isoniazid + Rifampicin only, for a total treatment duration of 12 months. 1, 2, 3
• Adjunctive corticosteroids (dexamethasone 6-12 mg/day or prednisolone 60-80 mg/day tapered over 6-8 weeks) should be added for all patients with tuberculous meningitis, particularly Stage II and III disease. 1, 3, 5

Common Pitfalls to Avoid

• Never extend streptomycin beyond the initial 2-month phase as it provides no benefit after meningeal inflammation subsides and only increases toxicity risk. 4
• Never use streptomycin as a routine fifth drug in addition to the standard four-drug regimen, as this adds no therapeutic advantage. 4
• Never use streptomycin in pregnant patients due to ototoxicity to the fetus; use ethambutol or ethionamide instead. 1, 7
• Never assume streptomycin alone provides adequate CNS coverage; it must always be part of a multi-drug regimen with agents that penetrate CSF well (isoniazid, pyrazinamide). 2, 3, 6

When Ethambutol is Preferred Over Streptomycin

• Ethambutol is the preferred fourth drug in most cases because it can be given orally, has no ototoxicity, is safe in pregnancy (unlike streptomycin), and can be continued throughout treatment if needed. 1, 2
• Ethambutol's main limitation is optic neuritis, which requires visual acuity monitoring—making it unsuitable for unconscious patients. 2, 4