Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients.
BACKGROUND
First-line treatment of influenza A 2009 H1N1 relies on neuraminidase inhibitors such as oseltamivir. Resistance conferred by the H275Y neuraminidase gene mutation is concerning and likely to increase.


OBJECTIVE
To characterize oseltamivir resistance in a hospital-based patient population.


METHODS
All available respiratory specimens positive for influenza A by direct fluorescent antibody, RT-PCR, or culture from patients at the University of Utah 5/09-12/09 were collected. Specimens were confirmed as 2009 H1N1 by the Utah Department of Health. RT-PCR and pyrosequencing were used to test for the H275Y mutation (CDC protocol). PyroMark Q24 AQ software (Qiagen, Valencia, CA, USA) was used to allow for quantitative H275Y mutation analysis. Medical records of patients with resistant virus were reviewed.


RESULTS
We tested 191 influenza A virus-positive samples from 187 unique patients. Fifty (27%) patients were hospitalized. Four patient specimens (2.1%) were found to carry the H275Y mutation. Three patients were hospitalized, representing 6% of inpatient samples tested. Three patients had undergone hematopoietic stem cell transplant in the past year. Two patients died. Their influenza viruses were confirmed to be oseltamivir-resistant at an independent reference laboratory and through the Center for Disease Control and Prevention (CDC). One patient reported no history of prior oseltamivir exposure.


CONCLUSIONS
Widespread oseltamivir resistance among 2009 H1N1 remains a potential threat. Rapid techniques, such as pyrosequencing, which has the additional benefit of identifying mixed mutant populations of virus, may play a key role in identifying at-risk individuals and potentially unsuspected cases. Targeted surveillance of immunocompromised patients will be critical toward improving future influenza planning and therapy.
Couturier
Brianne A
BA
ARUP Laboratories, Salt Lake City, UT, USA.
Bender
Jeffrey M
JM
Schwarz
Monica A
MA
Pavia
Andrew T
AT
Hanson
Kimberly E
KE
She
Rosemary C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006760:Hospitalization; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D000998:Antiviral Agents; D053139:Oseltamivir; D009439:Neuraminidase