Low penetration of caspofungin into cerebrospinal fluid following intravenous administration of standard doses

International Journal of Antimicrobial Agents
Volker StrengerChristian Urban

Abstract

The kinetics of caspofungin (CAS) in cerebrospinal fluid (CSF) following intravenous (i.v.) administration has been studied exclusively in animal models. Human data are missing so far. In this study, 13 CSF samples were obtained at different time points following i.v. infusion of CAS in ten paediatric haemato-/oncological patients (age range 1.0-14.2 years, median 8.6 years) without signs of central nervous system (CNS) infection (n = 10 samples) or with infectious meningitis (n = 3 samples). Serum samples were obtained concurrently. Liquid chromatography-tandem mass spectrometry was used for CAS quantification. Whilst CAS serum levels were in the expected range, varying between 0.6 and 20.3 µg/mL (median 7.0 µg/mL), 11 of 13 CSF levels were below the limit of detection of 0.084 µg/mL at 3.0-48.0 h (median 23.3 h) following i.v. infusion. Only two (of three) levels in patients with bacterial meningitis were above the limit of detection (0.3 µg/mL and 0.09 µg/mL, respectively). These results indicate the low capacity of CAS to penetrate into the CNS even in inflamed meninges. Monotherapy with standard doses of CAS appears not to be suitable for treatment of fungal CNS infections.

Citations

Jan 3, 2018·Current Opinion in Infectious Diseases·Roland NauHelmut Eiffert
Jan 6, 2018·The Journal of Antimicrobial Chemotherapy·Federico Pea, Russell E Lewis
Aug 15, 2019·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Andreas TrobischV Strenger
Apr 29, 2020·Antimicrobial Agents and Chemotherapy·Jana MarxRomuald Bellmann
Jan 25, 2020·Paediatric Drugs·Kevin J DownesNicole R Zane
Oct 17, 2019·Journal of Fungi·Elizabeth Dodds Ashley
Jul 25, 2021·Revista iberoamericana de micología·Rafael ZaragozaJavier Pemán

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