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• W4366240404 abstract "Human herpesvirus 6 (HHV-6) encephalitis is a severe complication of HSCT. HHV-6 infects the brains of most healthy individuals.1 The virus is reactivated by HSCT-related immunosuppression, which may result in HHV-6 encephalitis. Most cases occur 2–6 weeks after HSCT, with a reported incidence rate of 0%–11.6%. Further, there is a higher occurrence after cord blood transplantation (CBT).2 Among several antiviral drugs effective against HHV-6, foscarnet is recommended to treat HHV-6 encephalitis.3 Penetration of foscarnet into the CSF was studied in patients with AIDS.4,5 However, whether foscarnet penetrates the CSF to achieve an effective CSF concentration against HHV-6 in patients with post-HCST HHV-6 encephalitis remains unclear. Here, we describe three cases of HHV-6 encephalitis after HSCT, where the CSF concentration of foscarnet (Table 1) was measured through validated LC-tandem MS.6 This study was approved by the institutional ethics board of the Kobe City Medical Center General Hospital (approval number zn200421, 4 April 2020). In all three cases, HHV-6 DNA was detected in the CSF by PCR. Central nervous symptoms appeared after CBT, which had no other possible causes, and thus the patients were diagnosed with HHV-6 encephalitis. The therapeutic dose of foscarnet, adjusted according to renal function, was administered IV. CSF samples were obtained through lumbar puncture for HHV-6 DNA PCR and measurement of the CSF concentration of foscarnet. Foscarnet therapy markedly reduced the CSF levels of HHV-6 DNA in all three cases. Moreover, the median CSF concentration of foscarnet was 60.2 µM (range: 17.5–122 µM), which is consistent with previous reports on patients with AIDS [80 µM (range: 0–500 µM)].4 Therefore, the therapeutic foscarnet dose was substantiated to almost achieve the IC50 concentration of HHV-6 in vitro (6–83.2 μM)7 and reduced the HHV-6 DNA levels in the CSF, even in patients with post-HSCT HHV-6 encephalitis. Nevertheless, Cases 2 and 3, which involved a reduced foscarnet dosage according to renal function, had higher CSF concentrations than Case 1, suggesting that adjusting the dosage according to renal function does not reduce the resulting CSF concentration." @default.
• W4366240404 created "2023-04-20" @default.
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• W4366240404 date "2023-04-18" @default.
• W4366240404 modified "2023-09-27" @default.
• W4366240404 title "Cerebrospinal fluid concentration of foscarnet in patients with HHV-6 encephalitis after haematopoietic stem cell transplantation" @default.
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• W4366240404 doi "https://doi.org/10.1093/jac/dkad117" @default.
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