Cycloserine and Linezolid for Tuberculosis Meningitis: Pharmacokinetic Evidence of Potential Usefulness.
Clin Infect Dis
; 75(4): 682-689, 2022 09 10.
Article
em En
| MEDLINE
| ID: mdl-34849645
ABSTRACT
BACKGROUND:
The ability of antituberculosis drugs to cross the blood-brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF).METHODS:
We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration.RESULTS:
A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/mL with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/mL at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration.CONCLUSIONS:
Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Meníngea
/
Mycobacterium tuberculosis
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Infect Dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos