title: Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults.
abstract: The importance and significance of amantadine- or rimantadine-resistant influenza viruses in immunocompromised patients was studied in a population of adult bone marrow transplant (BMT) recipients and patients with leukemia prospectively cultured for respiratory viruses. Influenza A viruses were isolated from 29 patients with acute respiratory illness (14 BMT recipients and 15 patients with leukemia). Fifteen patients (52%) received amantadine (n = 4) or rimantadine (n = 11) therapy. All influenza isolates recovered from six patients shedding virus for > or = 3 days were screened for antiviral susceptibility; resistant isolates were further genetically characterized. Initial influenza isolates were susceptible to amantadine or rimantadine, but subsequent isolates from five of six patients were resistant. Influenza-associated mortality was similar among patients with and without documented antiviral resistance (2 of 5 vs. 5 of 24). We conclude that development of antiviral resistance in immunocompromised individuals should be considered when they have been treated with antivirals and have shed influenza virus for a prolonged period. Isolation procedures should be instituted for all immunocompromised patients with influenza, both during and after therapy with amantadine or rimantadine.
authors.affiliation: Acute Viral Respiratory Diseases Unit, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Englund
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.forename: P R
authors.initials: PR
authors.lastname: Wyde
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: R L
authors.initials: RL
authors.lastname: Atmar
authors.forename: J
authors.initials: J
authors.lastname: Tarrand
authors.forename: H
authors.initials: H
authors.lastname: Yousuf
authors.forename: H
authors.initials: H
authors.lastname: Regnery
authors.forename: A I
authors.initials: AI
authors.lastname: Klimov
authors.forename: N J
authors.initials: NJ
authors.lastname: Cox
authors.forename: E
authors.initials: E
authors.lastname: Whimbey
mesh_terms: D000328:Adult; D000547:Amantadine / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D004352:Drug Resistance, Microbial; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000209:etiology; D007938:Leukemia / Q000150:complications; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy / Q000209:etiology / Q000821:virology*; D012299:Rimantadine / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D012299:Rimantadine; D000547:Amantadine