Longitudinal characterization of herpes simplex virus (HSV) isolates acquired from different sites in an immune-compromised child: A new HSV thymidine kinase mutation associated with resistance

Andrew H. Karaba, Laura K. Cohen, Taly Glaubach, Sarah J. Kopp, Jennifer L Reichek, Hawke H Yoon, Xiaotian Zheng, William J Muller*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Herpes simplex virus resistance to acyclovir is well described in immune-compromised patients. Management of prolonged infection and recurrences in such patients may be problematic. Methods: A patient with neuroblastoma developed likely primary herpes gingivostomatitis shortly after starting a course of chemotherapy, with spread to the eye during treatment with acyclovir. Viral isolates were serially obtained from separate sites after treatment was begun and tested for susceptibility to acyclovir and foscarnet by plaque reduction and plating efficiency assays. The thymidine kinase and DNA polymerase genes from each isolate were sequenced. Results: Initial isolates from a throat swab, an oral lesion, and conjunctiva were resistant to acyclovir within 13 days of treatment. Subsequent isolates while on foscarnet were initially acyclovir-susceptible, but reactivation of an acyclovir-resistant isolate was subsequently documented while on acyclovir suppression. Genotypic analysis identified a previously unreported UL23 mutation in some resistant isolates. None of the amino acid changes identified in UL30 were associated with resistance. Conclusions: Phenotypic and genotypic antiviral resistance of herpes simplex isolates may vary from different compartments and over time in individual immune-compromised hosts, highlighting the importance of obtaining cultures from all sites. Phenotypic resistance testing should be considered for isolates obtained from at-risk patients not responding to first-line therapy. Empiric combination treatment with multiple antivirals could be considered in some situations.

Original languageEnglish (US)
Article numberpis009
Pages (from-to)116-124
Number of pages9
JournalJournal of the Pediatric Infectious Diseases Society
Volume1
Issue number2
DOIs
StatePublished - Jan 1 2012

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Acyclovir
Thymidine Kinase
Simplexvirus
Mutation
Foscarnet
Antiviral Agents
Therapeutics
Herpes Simplex
Conjunctiva
DNA-Directed DNA Polymerase
Pharynx
Neuroblastoma
Amino Acids
Recurrence
Drug Therapy
Infection
Genes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases

Cite this

@article{34a09fa9181c4023969f8301ffd46db6,
title = "Longitudinal characterization of herpes simplex virus (HSV) isolates acquired from different sites in an immune-compromised child: A new HSV thymidine kinase mutation associated with resistance",
abstract = "Background: Herpes simplex virus resistance to acyclovir is well described in immune-compromised patients. Management of prolonged infection and recurrences in such patients may be problematic. Methods: A patient with neuroblastoma developed likely primary herpes gingivostomatitis shortly after starting a course of chemotherapy, with spread to the eye during treatment with acyclovir. Viral isolates were serially obtained from separate sites after treatment was begun and tested for susceptibility to acyclovir and foscarnet by plaque reduction and plating efficiency assays. The thymidine kinase and DNA polymerase genes from each isolate were sequenced. Results: Initial isolates from a throat swab, an oral lesion, and conjunctiva were resistant to acyclovir within 13 days of treatment. Subsequent isolates while on foscarnet were initially acyclovir-susceptible, but reactivation of an acyclovir-resistant isolate was subsequently documented while on acyclovir suppression. Genotypic analysis identified a previously unreported UL23 mutation in some resistant isolates. None of the amino acid changes identified in UL30 were associated with resistance. Conclusions: Phenotypic and genotypic antiviral resistance of herpes simplex isolates may vary from different compartments and over time in individual immune-compromised hosts, highlighting the importance of obtaining cultures from all sites. Phenotypic resistance testing should be considered for isolates obtained from at-risk patients not responding to first-line therapy. Empiric combination treatment with multiple antivirals could be considered in some situations.",
author = "Karaba, {Andrew H.} and Cohen, {Laura K.} and Taly Glaubach and Kopp, {Sarah J.} and Reichek, {Jennifer L} and Yoon, {Hawke H} and Xiaotian Zheng and Muller, {William J}",
year = "2012",
month = "1",
day = "1",
doi = "10.1093/jpids/pis009",
language = "English (US)",
volume = "1",
pages = "116--124",
journal = "Journal of the Pediatric Infectious Diseases Society",
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TY - JOUR

T1 - Longitudinal characterization of herpes simplex virus (HSV) isolates acquired from different sites in an immune-compromised child

T2 - A new HSV thymidine kinase mutation associated with resistance

AU - Karaba, Andrew H.

AU - Cohen, Laura K.

AU - Glaubach, Taly

AU - Kopp, Sarah J.

AU - Reichek, Jennifer L

AU - Yoon, Hawke H

AU - Zheng, Xiaotian

AU - Muller, William J

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Background: Herpes simplex virus resistance to acyclovir is well described in immune-compromised patients. Management of prolonged infection and recurrences in such patients may be problematic. Methods: A patient with neuroblastoma developed likely primary herpes gingivostomatitis shortly after starting a course of chemotherapy, with spread to the eye during treatment with acyclovir. Viral isolates were serially obtained from separate sites after treatment was begun and tested for susceptibility to acyclovir and foscarnet by plaque reduction and plating efficiency assays. The thymidine kinase and DNA polymerase genes from each isolate were sequenced. Results: Initial isolates from a throat swab, an oral lesion, and conjunctiva were resistant to acyclovir within 13 days of treatment. Subsequent isolates while on foscarnet were initially acyclovir-susceptible, but reactivation of an acyclovir-resistant isolate was subsequently documented while on acyclovir suppression. Genotypic analysis identified a previously unreported UL23 mutation in some resistant isolates. None of the amino acid changes identified in UL30 were associated with resistance. Conclusions: Phenotypic and genotypic antiviral resistance of herpes simplex isolates may vary from different compartments and over time in individual immune-compromised hosts, highlighting the importance of obtaining cultures from all sites. Phenotypic resistance testing should be considered for isolates obtained from at-risk patients not responding to first-line therapy. Empiric combination treatment with multiple antivirals could be considered in some situations.

AB - Background: Herpes simplex virus resistance to acyclovir is well described in immune-compromised patients. Management of prolonged infection and recurrences in such patients may be problematic. Methods: A patient with neuroblastoma developed likely primary herpes gingivostomatitis shortly after starting a course of chemotherapy, with spread to the eye during treatment with acyclovir. Viral isolates were serially obtained from separate sites after treatment was begun and tested for susceptibility to acyclovir and foscarnet by plaque reduction and plating efficiency assays. The thymidine kinase and DNA polymerase genes from each isolate were sequenced. Results: Initial isolates from a throat swab, an oral lesion, and conjunctiva were resistant to acyclovir within 13 days of treatment. Subsequent isolates while on foscarnet were initially acyclovir-susceptible, but reactivation of an acyclovir-resistant isolate was subsequently documented while on acyclovir suppression. Genotypic analysis identified a previously unreported UL23 mutation in some resistant isolates. None of the amino acid changes identified in UL30 were associated with resistance. Conclusions: Phenotypic and genotypic antiviral resistance of herpes simplex isolates may vary from different compartments and over time in individual immune-compromised hosts, highlighting the importance of obtaining cultures from all sites. Phenotypic resistance testing should be considered for isolates obtained from at-risk patients not responding to first-line therapy. Empiric combination treatment with multiple antivirals could be considered in some situations.

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