title: Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: risk factors and prognostic significance.
abstract: Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex (females), unrelated donor graft, and graft-versus-host disease (GVHD) grade >/=2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet. Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resistant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC(50) values correlated inversely with those for acyclovir (P=.01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade >/=2 (P=.001) and the lack of ganciclovir prophylaxis (P=.01), with a higher nonrelapse mortality in the latter group (P<.0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.
authors.affiliation: Department of Haematology, Birmingham Heartlands Hospital, Birmingham, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: D
authors.initials: D
authors.lastname: Pillay
authors.forename: D
authors.initials: D
authors.lastname: Ratcliffe
authors.forename: P A
authors.initials: PA
authors.lastname: Cane
authors.forename: K E
authors.initials: KE
authors.lastname: Collingham
authors.forename: D W
authors.initials: DW
authors.lastname: Milligan
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000209:etiology; D006147:Guanine; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D000998:Antiviral Agents; C053539:penciclovir; D006147:Guanine; D015774:Ganciclovir; D000212:Acyclovir