Publication date: Jul 01, 2026
Bedaquiline, pretomanid, and linezolid (BPaL) is a 6-month regimen that has revolutionized treatment of multidrug-resistant (MDR) tuberculosis (TB). However, there is limited evidence of using BPaL to treat MDR tuberculous meningitis (TBM), a devastating illness that has high risk of mortality and permanent disability. A patient with fluoroquinolone-resistant pre-extensively drug-resistant (pre-XDR) TBM was cured with a 10-month regimen based on BPaL with clofazimine and cycloserine. Total concentrations of bedaquiline, pretomanid, and linezolid were measured in plasma and cerebrospinal fluid (CSF) via ultraperformance liquid chromatography. Unbound concentrations were estimated from plasma concentrations and CSF concentrations normalized to plasma protein concentrations using the Winter-Tozer formula. AUC (24-hour area under the curve) was calculated using the trapezoidal method. The CSF:plasma unbound AUC was 1. 48 and 0. 99 for pretomanid and linezolid, respectively. Pharmacokinetic/pharmacodynamic targets were achieved for pretomanid with CSF concentration above the critical concentration of 0. 5 mg/L throughout most of the dosing interval and linezolid AUC/minimum inhibitory concentration (MIC) of 171 for an MIC of 0. 5 mg/L. However, CSF concentrations of pretomanid and linezolid may be below target for strains with MICs >0. 5 mg/L. Estimated unbound peak concentrations in CSF in week 21 were comparable to plasma (0. 0034 mg/L and 0. 0032 mg/L, respectively), suggesting that therapeutic central nervous system concentrations of bedaquiline were achieved. Fluoroquinolone-resistant pre-XDR TBM was cured with 10 months of treatment based on BPaL with clofazimine and cycloserine. BPaL achieved therapeutic concentrations in CSF for most TB strains. Further research is required into optimal treatment and dosing of drug-resistant TBM.
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| Concepts | Keywords |
|---|---|
| bedaquiline | |
| cerebrospinal fluid | |
| pretomanid | |
| tuberculous meningitis |
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Bedaquiline |
| drug | DRUGBANK | Pretomanid |
| drug | DRUGBANK | Linezolid |
| disease | MESH | Tuberculous Meningitis |
| disease | MESH | tuberculosis |
| pathway | KEGG | Tuberculosis |
| drug | DRUGBANK | Clofazimine |
| drug | DRUGBANK | Cycloserine |
| drug | DRUGBANK | Methyl isocyanate |
| disease | MESH | strains |
| disease | MESH | multi-drug resistant tuberculosis |