Different drug-resistant influenza A(H3N2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in Italy

Background: Monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs. Objectives: Influenza A kinetics and the emergence of drug-resistant strains in hospitalized patients treated with oseltamivir were investigated. Study design: Sequential samples from oseltamivir-treated and -untreated hospitalized patients in the period November 2011 through April 2012 were analyzed. NA gene was sequenced in samples from oseltamivir treated patients. Clonal analysis of the viral population was performed in patients unresponsive to treatment. Viral kinetics was determined in 24 (14 immunocompromised and 10 immunocompetent) A(H3N2)-positive patients treated and 24 (10 immunocompromised and 14 immunocompetent) untreated patients. Results: Viral shedding was significantly reduced in treated vs untreated immunocompromised patients (7 vs 22 days, p<0.05, respectively). Viral load decreased significantly in immunocompromised and immunocompetent treated patients as compared with immunocompromised and immunocompetent untreated patients (0.73 and 0.93 vs 0.47 and 0.45 log(10)/day, p<0.05). In two (8.3%) treated patients with prolonged virus shedding, the oseltamivir resistance R292K mutation was revealed. In these patients, clonal analysis of the virus population showed the presence of additional oseltamivir-resistant mutants (E119V, N294S and deletion Del247-250). Conclusions: Oseltamivir resistance is reported for the first time in A(H3N2) virus strains during the 2011-2012 influenza season. Different drug-resistant viruses emerged in hospitalized immunocompromised patients showing prolonged virus shedding. (C) 2013 Elsevier B. V. All rights reserved.