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Infection due to acyclovir resistant herpes simplex virus in patients undergoing allogeneic hematopoietic stem cell
V Venard1, J N Dauendorffer, A S Carret
1Unité mixte de recherche 7565 UHP-CNRS, laboratoire de bactériologie-virologie, faculté de médecine, Vandoeuvre-lès-Nancy, France. veroniquevenard@voila.fr
Abstract:
Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving acyclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were acyclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valacyclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.
Insights
Bone marrow transplant patients can develop severe infections from acyclovir-resistant herpes simplex virus 1 (HSV-1). Monitoring antiviral resistance and evaluating new drugs like cidofovir are crucial for managing these difficult infections.
Area of Science:
- Virology
- Immunology
- Hematology
Background:
- Bone marrow transplant (BMT) recipients are susceptible to severe opportunistic infections.
- Herpes simplex virus 1 (HSV-1) infections can be particularly challenging in immunocompromised individuals.
- Antiviral drug resistance in HSV-1 is a growing concern in BMT patients.
Purpose of the Study:
- To report on severe acyclovir-resistant HSV-1 infections in BMT patients.
- To evaluate the efficacy of alternative antiviral agents against drug-resistant HSV-1 strains.
- To highlight the importance of monitoring antiviral resistance in this population.
Main Methods:
- Case series of four BMT patients with severe mucosal cutaneous HSV-1 infections.
- Antiviral susceptibility testing using the dye uptake method for acyclovir (ACV) and foscarnet.
- Thymidine kinase (TK) gene sequencing to investigate resistance mechanisms.
- Clinical assessment of treatment outcomes with valacyclovir and cidofovir.
Main Results:
- Four BMT patients presented with severe HSV-1 infections resistant to acyclovir.
- Three of the four HSV-1 isolates were also resistant to foscarnet.
- TK gene sequencing did not correlate with ACV resistance.
- Clinical cure was achieved in three patients with valacyclovir or cidofovir, but two later died of graft-versus-host disease.
- One patient died from extensive HSV-1 infection despite cidofovir treatment.
Conclusions:
- Severe HSV-1 infections resistant to multiple antiviral drugs can occur in BMT recipients.
- Monitoring herpes virus antiviral resistance is essential in immunocompromised patients.
- Novel antiviral drugs like cidofovir show potential for treating infections caused by drug-resistant HSV-1 strains.
- Graft-versus-host disease remains a significant mortality factor in BMT patients.