Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States

 

Nila J. Dharan, MD; Larisa V. Gubareva, PhD; John J. Meyer, MPH; Margaret Okomo-Adhiambo, PhD; Reginald C. McClinton, MPH; Steven A. Marshall, MS; Kirsten St. George, MAppSc, PhD; Scott Epperson, MPH; Lynnette Brammer, MPH; Alexander I. Klimov, PhD; Joseph S. Bresee, MD; Alicia M. Fry, MD, MPH; for the Oseltamivir-Resistance Working Group

JAMA. 2009;301(10):1034-1041. Published online March 2, 2009 (doi:10.1001/jama.2009.294).

ABSTRACT

 

Context  During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.

Objectives  To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.

Design, Setting, and Patients  Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.

Main Outcome Measures  Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.

Results  During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.

Conclusions  Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.

 

 


INTRODUCTION

 

 

 
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In January 2006, the US Centers for Disease Control and Prevention (CDC) recommended against the use of adamantanes due to a significant increase in resistance among circulating influenza A(H3N2) viruses.1 As a result, neuraminidase inhibitors (NAIs) became the only class of antiviral agents recommended for the treatment and prophylaxis of influenza virus infections in the United States.12 Since their introduction in 1999, the proportion of influenza viruses resistant to NAIs among circulating influenza viruses has been low, generally less than 1% of isolates tested worldwide.35

 

 
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