Rapid Emergence of Oseltamivir Resistance

EID Journal Home > Volume 16, Number 4–April 2010

Volume 16, Number 4–April 2010
Letter
Rapid Emergence of Oseltamivir Resistance
Cheng Len Sy, Susan Shin-Jung Lee, Ming-Tsan Liu, Hung-Ching Tsai, and Yao-Shen Chen
Author affiliations: Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (C.L. Sy, S.S.-J. Lee, H.-C. Tsai, Y.-S. Chen); National Yang-Ming University, Taipei, Taiwan (S.S.-J. Lee, H.-C. Tsai, Y.-S. Chen); and Centers for Disease Control, Taipei (M.-T. Liu)

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To the Editor: The influenza A pandemic (H1N1) 2009 virus has spread globally since it first appeared in Mexico in April 2009. This third influenza pandemic since the Spanish influenza pandemic of 1918 (1) has caused at least 400,000 infections within 6 months; estimated mortality rate is 1.2% (2). Emergence of oseltamivir resistance in the pandemic (H1N1) 2009 virus is a rising challenge to global control of the pandemic. So far, 39 oseltamivir-resistant pandemic (H1N1) 2009 viruses have been reported worldwide (3). Among the 32 resistant strains reported in October 2009, a total of 13 (41%) were associated with postexposure chemoprophylaxis and 16 (50%) were from samples of patients receiving oseltamivir (3). We report rapid emergence of resistance (H275Y mutation) in a patient, 4 days after early treatment with standard doses of oseltamivir for pandemic (H1N1) 2009 pneumonia.

On September 1, 2009, a 20-year-old man with mental retardation consulted the emergency department of Kaohsiung Veterans General Hospital after 1 day of fever, sore throat, and nonproductive cough. A rapid diagnostic antigen test (Quick Vue Influenza test; Quidel, San Diego, CA, USA) showed the man to be positive for influenza A. He was hospitalized for bilateral pneumonitis and treated with oseltamivir (75 mg 2×/day for 5 days), ampicillin/sulbactam, and erythromycin.
However, a progressive increase in bilateral perihilar interstitial infiltration developed on the third day, accompanied by increasing dyspnea. Influenza A pandemic (H1N1) 2009 virus was isolated from the patient's nasopharyngeal secretions on days 1 and 4 by using MDCK cells. After DNA sequence analysis of the neuraminidase gene, the mutation of H275Y was not found in the first isolate, but sequence analysis of the second isolate detected mixed populations (C/T) in the 823-nt position of the neuraminidase gene. Only a single pattern (T) was found from the cultured viruses, indicating a mixed quasispecies of oseltamivir-resistant and -susceptible viruses emerging after 4 days of oseltamivir treatment. The oseltamivir-resistant viruses become dominant in the cell culture–propagated viruses. Chan et al. reported a similar case in which the original clinical specimens contained a mixed population of variants, and oseltamivir-resistant viruses become dominant after the passage in MDCK cells (4).

Suggested Citation for this Article
Sy CL, Lee S S-J, Liu M-T, Tsai H-C, Chen Y-S. Rapid emergence of oseltamivir resistance [letter]. Emerg Infect Dis [serial on the Internet]. 2010 Apr [date cited]. http://www.cdc.gov/EID/content/16/4/723.htm

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DOI: 10.3201/eid1604.091706