Rapid acquisition of acyclovir resistance in an immunodeficient patient with herpes simplex encephalitis

Karrasch, Matthias; Liermann, Kristin; Betz, Boris; Wagner, Sabine; Scholl, Sebastian; Dahms, Christiane; Sauerbrei, Andreas; Kunze, Anja

doi:10.1016/j.jns.2017.11.024

Cited by 11 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The typical use of acyclovir and penciclovir often presents limitations due to their side effects and low efficacy, determined by drug-resistant strains. Viral resistance to ACV has been shown to be more common in immunocompromised patients undergoing long-term therapy, as seen for most other viral infections, highlighting the need for new drugs with novel mechanisms of action [39,40].…”

Section: Discussionmentioning

confidence: 99%

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

et al. 2021

View full text Add to dashboard Cite

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In contrast, guidelines recommend intravenous acyclovir for 3 weeks in immunocompromised patients and a retap thereafter to exclude persistent infection [38]. In this regard, there is ongoing research to assess whether HSV strains in immunodeficient patients are more prone to developing acyclovir resistance [39]. With the development of ischemic stroke in territories supplied by distinct cerebral arteries in febrile neutropenia, we needed to rule out systemic, thoracic and abdominal infectious foci, endocarditis and cardiac arrhythmia as a potential embolic source.…”

Section: Discussionmentioning

confidence: 99%

Cerebral HSV-1 Vasculitis as a Fatal Complication of Immunosuppression in Non-Hodgkin´s Lymphoma: A Case Report and Review of the Literature

Nardone

Carnicelli²,

Brigo³

et al. 2020

Pathogens

View full text Add to dashboard Cite

Patients with lymphoma are predisposed to infection because of the immunocompromised state related to the disease itself and as a consequence of chemo-/radiotherapy. Here, we report a case of Herpes-simplex virus encephalitis (HSE) in an immunosuppressed patient with splenic marginal zone lymphoma (SMZL), a rare indolent variant of non-Hodgkin´s lymphoma (NHL). The course was complicated febrile neutropenia and HSV-1-related cerebral vasculitis causing progressive ischemic stroke. This case illustrates the expanding spectrum of atypical clinical and radiological manifestations of HSE in patients treated with myelotoxic drugs. Moreover, we summarize the few central nervous system manifestations of SMZL reported in the literature and discuss distinct causes of neurological deterioration in patients with NHL.

show abstract

“…Omeprazole may not exert general immunosuppressive effects in the same way as hydrocortisone but to more specifically increase acyclovir activity. In immunodeficiency individuals, HSV-1 and -2 infections are often associated with more severe disease, and resistance formation to acyclovir is a severe problem (Piret and Boivin, 2016; Karrasch et al, 2018). Moreover, ocular HSV infection is a major cause of blindness in industrialized countries (Klysik et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Omeprazole Increases the Efficacy of Acyclovir Against Herpes Simplex Virus Type 1 and 2

et al. 2019

View full text Add to dashboard Cite

Omeprazole was shown to improve the anti-cancer effects of the nucleoside analogue 5-fluorouracil. Here, we combined omeprazole with the antiviral nucleoside analogues ribavirin and acyclovir. Omeprazole did not affect the antiviral effects of ribavirin in non-toxic concentrations up to 80 μg/mL but increased the acyclovir-mediated effects on herpes simplex virus 1 and 2 (HSV-1 and -2) replication in a dose-dependent manner. Omeprazole alone reduced HSV-1 and -2 titers [but not HSV-induced formation of cytopathogenic effects (CPE)] at concentrations ≥40 μg/mL. However, it exerted substantially stronger effects on acyclovir activity and also increased acyclovir activity at lower concentrations that did not directly interfere with HSV replication. Omeprazole 80 μg/mL caused a 10.8-fold (Vero cells) and 47.7-fold (HaCaT cells) decrease of the acyclovir concentrations that reduced HSV-1-induced CPE formation by 50% (IC50). In HSV-2-infected cells, omeprazole 80 μg/mL reduced the acyclovir IC50 by 7.3- (Vero cells) and 12.9-fold (HaCaT cells). In HaCaT cells, omeprazole 80 μg/mL reduced the HSV-1 titer in the presence of acyclovir 1 μg/mL by 1.6 × 105-fold and the HSV-2 titer in the presence of acyclovir 2 μg/mL by 9.2 × 103-fold. The proton pump inhibitors pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole increased the antiviral effects of acyclovir in a similar fashion as omeprazole, indicating this to be a drug class effect. In conclusion, proton pump inhibitors increase the anti-HSV activity of acyclovir and are candidates for antiviral therapies in combination with acyclovir, in particular for topical preparations for the treatment of immunocompromised individuals who are more likely to suffer from severe complications.

show abstract

Rapid acquisition of acyclovir resistance in an immunodeficient patient with herpes simplex encephalitis

Cited by 11 publications

References 4 publications

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

Cerebral HSV-1 Vasculitis as a Fatal Complication of Immunosuppression in Non-Hodgkin´s Lymphoma: A Case Report and Review of the Literature

Omeprazole Increases the Efficacy of Acyclovir Against Herpes Simplex Virus Type 1 and 2

Contact Info

Product

Resources

About