Oseltamivir Resistance and Pandemic (H1N1) 2009 | CDC EID

EID Journal Home > Volume 16, Number 7–July 2010

Volume 16, Number 7–July 2010
Synopsis
Oseltamivir Resistance in Adult Oncology and Hematology Patients Infected with Pandemic (H1N1) 2009 Virus, Australia
Adrian R. Tramontana, Biju George, Aeron C. Hurt, Joseph S. Doyle, Katherine Langan, Alistair B. Reid, Janet M. Harper, Karin Thursky, Leon J. Worth, Dominic E Dwyer, C. Orla Morrissey, Paul D.R. Johnson, Kirsty L. Buising, Simon James Harrison, John F. Seymour, Patricia E. Ferguson, Bin Wang, Justin T. Denholm, Allen C. Cheng, and Monica Slavin
Author affiliations: Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia (A.R. Tramontana, K. Thursky, L.J. Worth, S.J. Harrison, J.F. Seymour, M. Slavin); Western Hospital, Footscray, Victoria, Australia (A.R. Tramontana); Westmead Hospital, Sydney, New South Wales, Australia (B. George, D.E. Dwyer, B. Wang), World Health Organization Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia (A.C. Hurt); The Alfred Hospital, Prahran, Victoria, Australia (J.S. Doyle, C.O. Morrissey); Austin Health, Heidelberg, Victoria, Australia (K. Langan, P.D.R. Johnson); St. Vincent's Hospital, Melbourne, Victoria, Australia (A.B. Reid, K.L. Buising); Royal Melbourne Hospital, Melbourne (J.M. Harper, J.T. Denholm, M. Slavin); Centre for Infectious Diseases and Microbiology, Sydney (P.E. Ferguson); and Monash University, Prahran (A.C. Cheng)

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Abstract
We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after >4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
Immunocompromised patients are at risk for serious complications from seasonal influenza (1). This group of patients has also been disproportionately represented among those with severe infections from influenza A pandemic (H1N1) 2009, comprising 3.4%–19.6% of patients admitted to intensive care units in case series from North America (2–4).

The protective effect of seasonal influenza vaccination is reduced in patients with hematologic malignancy and recipients of an allogeneic hematopoietic stem cell transplant (HSCT) (5,6). Therefore, these patients are likely to remain at increased risk for complications from the pandemic (H1N1) 2009 virus, despite the availability of an effective vaccine. Furthermore, the emergence of resistance to neuraminidase inhibitors may limit the utility of prophylaxis in this population (7–12).

During 2009, the predominant strain of influenza in Australia was influenza A pandemic (H1N1) 2009 virus (13,14). In the state of Victoria, after the initial 3 months of community transmission of pandemic (H1N1) 2009 virus, 50% of patients who died had an underlying hematologic malignancy (15). We describe in detail the clinical features, treatment, and outcomes of immunocompromised patients hospitalized in 6 tertiary centers in Australia during winter 2009.

Study Design and Population
Six Australian tertiary centers, 5 in Melbourne, Victoria, and 1 in Sydney, New South Wales (NSW), participated in the study. The 5 centers in Melbourne provide most specialist adult hematology services to the state of Victoria (population 5.4 million), and 2 of these centers perform all allogeneic HSCTs for the state. The participating Sydney center is the largest of 2 centers that perform adult allogeneic HSCT for the state of NSW (population 7 million). Approval for this study was obtained from human research ethics committees of each center.

Patients were included in the study if they had the following characteristics: 1) >18 years of age hospitalized at 1 of the 5 Melbourne study centers during May 1–August 30, 2009, or hospitalized at the Sydney center during May 1–September 15, 2009; 2) recipient of an HSCT or had an underlying malignancy (hematologic or solid tumor); and 3) had laboratory-confirmed pandemic (H1N1) 2009 virus infection identified by nucleic acid testing (NAT) during their hospital stay. At each center, investigators were directly involved in active surveillance and management of patients with pandemic (H1N1) 2009, allowing cases to be identified. Data were retrospectively abstracted onto standardized case record forms.

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