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Cerebrospinal fluid concentrations of ethionamide in children with tuberculous meningitis
1Department of Pediatrics, Tygerberg Hospital, South Africa.
Insights
Higher ethionamide doses are effective in treating childhood tuberculous meningitis. A 20 mg/kg daily dose achieved therapeutic cerebrospinal fluid ethionamide concentrations in most pediatric tuberculous meningitis patients.
Area of Science:
- Pediatric infectious diseases
- Neuroscience
- Pharmacology
Background:
- Tuberculous meningitis (TBM) is a severe infection in children.
- Raised intracranial pressure (ICP) is a common complication of TBM.
- Optimizing antimicrobial drug concentrations in cerebrospinal fluid (CSF) is crucial for effective treatment.
Purpose of the Study:
- To determine ethionamide concentrations in the CSF of children with TBM and raised ICP.
- To evaluate the efficacy of different ethionamide dosages in achieving therapeutic CSF levels.
Main Methods:
- CSF ethionamide levels were measured in 18 children with TBM.
- Specimens were collected before and after ICP monitoring.
- Dosages of 15 mg/kg and 20 mg/kg were administered and analyzed.
Main Results:
- A 15 mg/kg dose of ethionamide failed to reach the target CSF concentration (2.5 µg/ml) in 73% of cases.
- A 20 mg/kg dose achieved the target concentration in 85% of cases.
- CSF ethionamide levels were assessed in relation to ICP monitoring.
Conclusions:
- A single daily dosage of 20 mg/kg ethionamide is recommended for initial TBM treatment in children.
- This dosage is particularly important when isoniazid-resistant Mycobacterium tuberculosis is suspected.
- Achieving adequate CSF drug concentrations is vital for TBM management in pediatric patients.
Abstract:
Cerebrospinal fluid ethionamide concentrations were determined in 18 children (median age 26.5 months) with tuberculous meningitis complicated by raised intracranial pressure. Lumbar spinal fluid specimens were obtained before and after weekly hour-long monitoring of intracranial pressure. Thirty-five paired and four single specimens were evaluated. A dosage schedule of 15 mg/kg was used on 26 occasions, and a spinal fluid ethionamide concentration of 2.5 micrograms/ml, the in vitro minimal inhibitory concentration for Mycobacterium tuberculosis, was exceeded on only seven occasions (27%). A dosage of 20 mg/kg was administered on 13 occasions, and in only two instances (15%) was a concentration of 2.5 micrograms/ml not achieved. Ethionamide in a single daily dosage of 20 mg/kg should be considered for the initial treatment of tuberculous meningitis when the presence of isoniazid-resistant M. tuberculosis cannot be excluded.