Amantadine/rimantadine-resistant influenza a virus isolates (R-Flu) from different patient populations

The development of R-Flu in clinical settings following amantadine/rimantadine (A/R) therapy has been reported; the frequency of resistance (res) in various patient populations is not clear. We studied 110 influenza A isolates collected between 1993-1997 from symptomatic individuals in three settings: 20 untreated oupatients of all ages (20 isolates), 9 hospitalized children treated and untreated with A/R (16 isolates), and 49 immunocompromised (IC) adults receiving care at a cancer center (74 isolates), including both A/R treated and untreated patients. Res was determined using a bioassay with a cutoff of 2 ug/ml rimantadine and/or PCR amplification of the M2 region of influenza A with subsequent endonuclease digestion. R-Flu was not found in outpatients or hospitalized children but was documented in 14/49 (29%) IC adults, most of whom were known to have received prior A/R therapy. R-Flu may develop frequently in IC patients, is associated with symptomatic disease, and could potentially interfere with antiviral therapy.