VZV meningoencephalitis treated with ganciclovir.
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
VZV meningoencephalitis treated with ganciclovir.
Auteur(s) :
Collet, Aurore [Auteur]
Centre Hospitalier [Douai, Nord]
Baes, D. [Auteur]
Mambie, A. [Auteur]
Hembert, K. [Auteur]
Boulle, C. [Auteur]
Gana, I. [Auteur]
Lemaire, X. [Auteur]
Centre Hospitalier [Douai, Nord]
Baes, D. [Auteur]
Mambie, A. [Auteur]
Hembert, K. [Auteur]
Boulle, C. [Auteur]
Gana, I. [Auteur]
Lemaire, X. [Auteur]
Titre de la revue :
Médecine et Maladies Infectieuses
Nom court de la revue :
Med Mal Infect
Numéro :
50
Pagination :
444-445
Éditeur :
Elsevier
Date de publication :
2024-01-30
ISSN :
1769-6690
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
1. Introduction
Varicella-zoster virus (VZV) meningoencephalitis is frequently associated with neurological complications, and often present without skin rash. Treatment must be urgently administered.
Intravenous ...
Lire la suite >1. Introduction Varicella-zoster virus (VZV) meningoencephalitis is frequently associated with neurological complications, and often present without skin rash. Treatment must be urgently administered. Intravenous (IV) acyclovir is the reference treatment of VZV meningoencephalitis [1] but no guidelines are available for alternative treatments in cases of adverse events, particularly renal impairment in elderly patients [2]. To the best of our knowledge, we report the first case of VZV meningoencephalitis successfully treated with ganciclovir after acute renal failure due to acyclovir treatment. 2. Case report An 87-year-old woman was admitted to the emergency department for fever and consciousness disorders. She presented with headache, aphasia, and dizziness without any sign of meningeal irritation. C-reactive protein level was high (88.5 mg/L) and procalcitonin level was 0.15 ng/L. Brain magnetic resonance imaging (MRI) only revealed leukoencephalopathy lesions. Cerebrospinal fluid (CSF) examination revealed 352 × 106/L white blood cell (WBC) count with 12% of neutrophils, 23% of lymphocytes, and 65% of monocytes; high protein concentration (196 mg/dL), normal glucose level; and normal red blood cell count (< 1.106/L). The direct examination was negative. The patient was transferred to the intensive care unit due to low blood pressure (80/40 mmHg). The clinical course rapidly improved on acyclovir (10 mg/kg three times a day, each infused for 3 hours) with rapid fever and neurological disorder resolution. CSF and blood culture were both sterile. On day 4 of treatment, the patient's condition worsened. She exhibited clouding of consciousness and acute renal failure with oligoanuria. Positive result to the VZV PCR assay in CSF was received at that time. The brain CT scan was normal. Acyclovir blood dosage was 19.27 mg/L 20 hours and 40 minutes after the last infusion, suggesting an excessive dosage (residual concentration objective around 1.125 mg/L, corresponding to viral IC50). Acute tubular necrosis and encephalopathy due to acyclovir was suggested as diagnosis, and was aggravated by co-treatment with a high dose of amoxicillin. The acyclovir treatment was discontinued, and intermittent hemodialysis was started. For the management of VZV meningoencephalitis, we switched acyclovir for ganciclovir at the dose of 1.25 mg/kg three times a week, injected after dialysis. The patient underwent three intermittent dialysis sessions, with improvement of the renal function. Neurological status also improved. Treatment with ganciclovir was continued for three weeks, but the dose was increased to 1.25 mg/kg per day and then to 2.5 mg/kg per day after renal function improvement. A second lumbar puncture was performed on day 13 of treatment, and showed WBC decrease (56 × 106/L, 94% of lymphocytes, 6% of monocytes), almost normal protein concentration (53 mg/dL), with a negative VZV PCR in favor of laboratory response to ganciclovir. Ganciclovir dosage was 1.633 mg/L in plasma (residual concentration 41 hours after intake, objective between 0.5–3 mg/L) and 0.690 mg/L in CSF (residual concentration 41 hours after intake, no objective defined). Infectious and neurological outcomes were favorable. The patient underwent cognitive assessment one month after discharge, which was normal (Mini Mental State 30/30). Control brain MRI did not reveal sequelae of meningoencephalitis. 3. Discussion VZV is an alpha herpesvirus potentially associated with severe central nervous system infections and death. However, as no comparative study is available, IV acyclovir is the drug of choice for the treatment of this infection [3]. Nevertheless, acyclovir is associated with two main adverse effects. Acute kidney injury (AKI) can occur in up to 50% of cases. Independent risk factors for AKI are diabetes, concomitant use of non-steroidal anti-inflammatory drugs and vancomycin [4]. None of these conditions were observed in our patient. Short-duration infusions may also cause renal failure and the product should be infused within at least one hour [5]. We therefore decided to infuse acyclovir over three hours and can conclude that AKI may occur without risk factors. Acyclovir can also cause neurotoxicity, which can be mistaken for resurgence of viral encephalopathy. Acyclovir should be discontinued and replaced in patients presenting these adverse effects. Ganciclovir could be an alternative according to the Infectious Diseases Society of America (IDSA) [3]. Considering the lack of clinical experience with ganciclovir in CNS infections, the American Academy of Pediatrics Committee on infectious diseases recommends using ganciclovir with close monitoring and follow up of HSV or VZV PCR in CSF. Although no clinical experience is available with ganciclovir in VZV CNS infections, the drug has been assessed in other herpesvirus CNS infections. Ganciclovir proved effective in human herpesvirus 6 (HHV6) encephalitis in three patients [6] and in cytomegalovirus (CMV) encephalitis in a neonatal population [7]. Our staff already reported a case of herpes simplex virus (HSV) meningoencephalitis successfully treated with ganciclovir [8]. Ganciclovir inhibitory concentrations (IC50) for VZV are lower than acyclovir (IC50 0.8–5.2 μg/mL for acyclovir, IC50 0.2–2.8 μg/mL for ganciclovir) [9]. It has been proved that ganciclovir CSF concentration could reach HHV6 IC50 and be effective in treating this infection [6]. Acyclovir penetration in CSF was previously reported to be 5% [10] and 17% for ganciclovir [11]. In our case patient, ganciclovir seemed to have good penetration in CSF, approximately 50% according to our dosages in blood and CSF. This led to CSF biochemistry normalization and to negative VZV PCR in CSF. Ganciclovir is known to cause adverse effects, particularly bone marrow toxicity with cytopenia. However, no adverse effect was observed in our patient. 4. Conclusion In case of adverse effects or contraindications to acyclovir, ganciclovir seems to be an acceptable alternative treatment in patients presenting with VZV meningoencephalitis.Lire moins >
Lire la suite >1. Introduction Varicella-zoster virus (VZV) meningoencephalitis is frequently associated with neurological complications, and often present without skin rash. Treatment must be urgently administered. Intravenous (IV) acyclovir is the reference treatment of VZV meningoencephalitis [1] but no guidelines are available for alternative treatments in cases of adverse events, particularly renal impairment in elderly patients [2]. To the best of our knowledge, we report the first case of VZV meningoencephalitis successfully treated with ganciclovir after acute renal failure due to acyclovir treatment. 2. Case report An 87-year-old woman was admitted to the emergency department for fever and consciousness disorders. She presented with headache, aphasia, and dizziness without any sign of meningeal irritation. C-reactive protein level was high (88.5 mg/L) and procalcitonin level was 0.15 ng/L. Brain magnetic resonance imaging (MRI) only revealed leukoencephalopathy lesions. Cerebrospinal fluid (CSF) examination revealed 352 × 106/L white blood cell (WBC) count with 12% of neutrophils, 23% of lymphocytes, and 65% of monocytes; high protein concentration (196 mg/dL), normal glucose level; and normal red blood cell count (< 1.106/L). The direct examination was negative. The patient was transferred to the intensive care unit due to low blood pressure (80/40 mmHg). The clinical course rapidly improved on acyclovir (10 mg/kg three times a day, each infused for 3 hours) with rapid fever and neurological disorder resolution. CSF and blood culture were both sterile. On day 4 of treatment, the patient's condition worsened. She exhibited clouding of consciousness and acute renal failure with oligoanuria. Positive result to the VZV PCR assay in CSF was received at that time. The brain CT scan was normal. Acyclovir blood dosage was 19.27 mg/L 20 hours and 40 minutes after the last infusion, suggesting an excessive dosage (residual concentration objective around 1.125 mg/L, corresponding to viral IC50). Acute tubular necrosis and encephalopathy due to acyclovir was suggested as diagnosis, and was aggravated by co-treatment with a high dose of amoxicillin. The acyclovir treatment was discontinued, and intermittent hemodialysis was started. For the management of VZV meningoencephalitis, we switched acyclovir for ganciclovir at the dose of 1.25 mg/kg three times a week, injected after dialysis. The patient underwent three intermittent dialysis sessions, with improvement of the renal function. Neurological status also improved. Treatment with ganciclovir was continued for three weeks, but the dose was increased to 1.25 mg/kg per day and then to 2.5 mg/kg per day after renal function improvement. A second lumbar puncture was performed on day 13 of treatment, and showed WBC decrease (56 × 106/L, 94% of lymphocytes, 6% of monocytes), almost normal protein concentration (53 mg/dL), with a negative VZV PCR in favor of laboratory response to ganciclovir. Ganciclovir dosage was 1.633 mg/L in plasma (residual concentration 41 hours after intake, objective between 0.5–3 mg/L) and 0.690 mg/L in CSF (residual concentration 41 hours after intake, no objective defined). Infectious and neurological outcomes were favorable. The patient underwent cognitive assessment one month after discharge, which was normal (Mini Mental State 30/30). Control brain MRI did not reveal sequelae of meningoencephalitis. 3. Discussion VZV is an alpha herpesvirus potentially associated with severe central nervous system infections and death. However, as no comparative study is available, IV acyclovir is the drug of choice for the treatment of this infection [3]. Nevertheless, acyclovir is associated with two main adverse effects. Acute kidney injury (AKI) can occur in up to 50% of cases. Independent risk factors for AKI are diabetes, concomitant use of non-steroidal anti-inflammatory drugs and vancomycin [4]. None of these conditions were observed in our patient. Short-duration infusions may also cause renal failure and the product should be infused within at least one hour [5]. We therefore decided to infuse acyclovir over three hours and can conclude that AKI may occur without risk factors. Acyclovir can also cause neurotoxicity, which can be mistaken for resurgence of viral encephalopathy. Acyclovir should be discontinued and replaced in patients presenting these adverse effects. Ganciclovir could be an alternative according to the Infectious Diseases Society of America (IDSA) [3]. Considering the lack of clinical experience with ganciclovir in CNS infections, the American Academy of Pediatrics Committee on infectious diseases recommends using ganciclovir with close monitoring and follow up of HSV or VZV PCR in CSF. Although no clinical experience is available with ganciclovir in VZV CNS infections, the drug has been assessed in other herpesvirus CNS infections. Ganciclovir proved effective in human herpesvirus 6 (HHV6) encephalitis in three patients [6] and in cytomegalovirus (CMV) encephalitis in a neonatal population [7]. Our staff already reported a case of herpes simplex virus (HSV) meningoencephalitis successfully treated with ganciclovir [8]. Ganciclovir inhibitory concentrations (IC50) for VZV are lower than acyclovir (IC50 0.8–5.2 μg/mL for acyclovir, IC50 0.2–2.8 μg/mL for ganciclovir) [9]. It has been proved that ganciclovir CSF concentration could reach HHV6 IC50 and be effective in treating this infection [6]. Acyclovir penetration in CSF was previously reported to be 5% [10] and 17% for ganciclovir [11]. In our case patient, ganciclovir seemed to have good penetration in CSF, approximately 50% according to our dosages in blood and CSF. This led to CSF biochemistry normalization and to negative VZV PCR in CSF. Ganciclovir is known to cause adverse effects, particularly bone marrow toxicity with cytopenia. However, no adverse effect was observed in our patient. 4. Conclusion In case of adverse effects or contraindications to acyclovir, ganciclovir seems to be an acceptable alternative treatment in patients presenting with VZV meningoencephalitis.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
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CHU Lille
Inserm
CHU Lille
Collections :
Date de dépôt :
2024-01-31T22:16:40Z
2024-06-05T10:36:04Z
2024-06-05T10:36:04Z