Acyclovir resistance in herpes simplex virus type I encephalitis: a case report

Bergmann, Melanie; Beer, Ronny; Kofler, Mario; Helbok, Raimund; Pfausler, Bettina; Schmutzhard, Erich

doi:10.1007/s13365-016-0489-5

Cited by 28 publications

(15 citation statements)

References 15 publications

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“…Furthermore, as demonstrated in our model, PTV therapy due to the different mode of action would allow for treatment of ACV-resistant infections, which also have been reported for HSV encephalitis (Kakiuchi, et. al., 2012; Schepers, et.al, 2014; Bergmann et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

et al. 2018

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Pritelivir, a helicase-primase inhibitor, has excellent in vitro and in vivo activity against human herpes simplex virus (HSV). Mice lethally infected with HSV type 1 or 2, including acyclovir-resistant strains, were treated 72 h after infection for 7 days with pritelivir or acyclovir. Both drugs were administered orally twice daily either alone or in combination. Dosages of pritelivir from 0.3 to 30 mg/kg reduced mortality (P < 0.001) against HSV-1, E-377. With an acyclovir resistant HSV-1, 11360, pritelivir at 1 and 3 mg/kg increased survival (P < 0.005). With HSV-2, MS infected mice, all dosages higher than the 0.3 mg/kg dose of pritelivir were effective (P < 0.005). For acyclovir resistant HSV-2, strain 12247, pritelivir dosages of 1-3 mg/kg significantly improved survival (P < 0.0001). Combination therapies of pritelivir at 0.1 or 0.3 mg/kg/dose with acyclovir (10 mg/kg/dose) were protective (P < 0.0001) when compared to the vehicle treated group against HSV-2, strain MS (in line with previous data using HSV-1). An increased mean days to death (P < 0.05) was also observed and was indicative of a potential synergy. Pharmacokinetic studies were performed to determine pritelivir concentrations and a dose dependent relationship was found in both plasma and brain samples regardless of infection status or time of initiation of dosing. In summary, pritelivir was shown to be active when treatment was delayed to 72 h post viral inoculation and appeared to synergistically inhibit mortality in this model in combination with acyclovir. We conclude pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis.

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Section: Discussionmentioning

confidence: 99%

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

et al. 2018

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“…The emergence of HSV strains resistant to acyclovir has been very rarely observed in patients treated for HSE (47)(48)(49)(50)(51)(52)(53)(54). Antiviral drug resistance may be suspected in patients who do not respond to treatment or who develop neurological deterioration despite a full course of acyclovir.…”

Section: Complications After Antiviral Therapy Viral Resistance To Acmentioning

confidence: 99%

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Piret

Boivin

2020

Clin Microbiol Rev

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SUMMARY Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

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“…Relapses may occur in as high as 5% of cases 54 . Resistance to acyclovir is rare (about 0.5% in immunocompetent patients) 58 . Foscarnet is used for acyclovir-resistant HSE 59 .…”

Section: Specific Therapymentioning

confidence: 99%

Understanding and managing acute encephalitis

Kumar

2020

F1000Res

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Encephalitis is an important cause of morbidity, mortality, and permanent neurologic sequelae globally. Causes are diverse and include viral and non-viral infections of the brain as well as autoimmune processes. In the West, the autoimmune encephalitides are now more common than any single infectious cause, but, in Asia, infectious causes are still more common. In 2006, the World Health Organization coined the term “acute encephalitis syndrome”, which simply means acute onset of fever with convulsions or altered consciousness or both. In 2013, the International Encephalitis Consortium set criteria for diagnosis of encephalitis on basis of clinical and laboratory features. The most important infectious cause in the West is herpes simplex virus, but globally Japanese encephalitis (JE) remains the single largest cause. Etiologic diagnosis is difficult because of the large number of agents that can cause encephalitis. Also, the responsible virus may be detectable only in the brain and is either absent or transiently found in blood or cerebrospinal fluid (CSF). Virological diagnosis is complex, expensive, and time-consuming. Different centres could make their own algorithms for investigation in accordance with the local etiologic scenarios. Magnetic resonance imaging (MRI) and electroencephalography are specific for few agents. Clinically, severity may vary widely. A severe case may manifest with fever, convulsions, coma, neurologic deficits, and death. Autoimmune encephalitis (AIE) includes two major categories: (i) classic paraneoplastic limbic encephalitis (LE) with autoantibodies against intracellular neuronal antigens (Eg: Hu and Ma2) and (ii) new-type AIE with autoantibodies to neuronal surface or synaptic antigens (Eg: anti-N-methyl-D-aspartate receptor). AIE has prominent psychiatric manifestations: psychosis, aggression, mutism, memory loss, euphoria, or fear. Seizures, cognitive decline, coma, and abnormal movements are common. Symptoms may fluctuate rapidly. Treatment is largely supportive. Specific treatment is available for herpesvirus group and non-viral infections. Various forms of immunotherapy are used for AIE.

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Acyclovir resistance in herpes simplex virus type I encephalitis: a case report

Cited by 28 publications

References 15 publications

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Understanding and managing acute encephalitis

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