Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient

• Published in: Bone marrow transplantation (Basingstoke) Vol. 28; no. 8; pp. 799 - 801
• Main Authors: ARNULF, B, CHEBBI, F, LEFRERE, F, AIT ARKOUB, Z, VARET, B, FILLET, A. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.10.2001
• Subjects: Acyclovir; Acyclovir - pharmacology; Acyclovir - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic Agents, Alkylating - therapeutic use; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Combined Modality Therapy; Cyclosporine - therapeutic use; Cytarabine - therapeutic use; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - etiology; Cytosine - analogs & derivatives; Cytosine - pharmacology; Disease resistance; DNA polymerase; DNA-directed DNA polymerase; Drug Resistance, Viral; Fatal Outcome; Foscarnet; Foscarnet - pharmacology; Foscarnet - therapeutic use; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Herpes Genitalis - complications; Herpes Genitalis - drug therapy; Herpes Genitalis - virology; Herpes simplex; Herpes Simplex - complications; Herpes Simplex - drug therapy; Herpes Simplex - virology; Herpes viruses; Humans; Hydroxyurea - therapeutic use; Immunocompromised Host; Immunosuppressive Agents - therapeutic use; Infections; Interferons - therapeutic use; Kinases; Lesions; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Male; Medical sciences; Methotrexate - therapeutic use; Middle Aged; Mutation; Nonsense mutation; Nucleotides; Organophosphonates; Organophosphorus Compounds - pharmacology; Penis; Pharmacology. Drug treatments; Simplexvirus - drug effects; Simplexvirus - isolation & purification; Stem cell transplantation; Stop codon; Thymidine; Thymidine kinase; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - adverse effects; Transplants & implants; Viruses; Whole-Body Irradiation - adverse effects; Drug susceptibility test; Indication; Virological exploration; Alphaherpesvirinae; Homograft; Herpesvirus hominis 2; Aciclovir; Bone marrow; Antiviral; Complication; Graft; Mucocutaneous; Clinical isolate; Opportunistic infection; Thymidine kinase; Enzyme; Unrelated donor; Herpesviridae; Transferases; Foscarnet sodium; In vitro; Infection; Virus; Immunosuppression; Treatment; Viral disease
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1703233

A 45-year-old matched unrelated BMT recipient had sequential mucocutaneous herpes simplex virus (HSV) type 2 infections. Five months after BMT, a penile lesion occurred and was cured using acyclovir, as expected from in vitro susceptibility results. The same lesion recurred 1 month later but worsened with acyclovir. The HSV isolate was resistant to acyclovir (IC(50) = 105 microM), and a nucleotide (G) was added to the thymidine kinase gene leading to a premature stop codon. The lesion improved markedly with foscarnet. During this treatment a second HSV infection occurred on the buttocks 2 weeks after the first one and healed completely with acyclovir. This course correlated with in vitro results of the buttock HSV isolate which was foscarnet-resistant (IC(50) = 300 microg/ml) and acyclovir-sensitive. Surprisingly, no mutation gene of the foscarnet-resistant isolate was detected in the DNA polymerase gene. This case shows that an HSV acyclovir-resistant infection may be followed by an acyclovir-sensitive one. Determination of antiviral susceptibility is needed to monitor the treatment of various HSV infections in immunocompromised BMT recipients.