Oseltamivir-resistant 2009 H1N1 increased among immunocompromised patients

Calatayud L. Emerg Infect Dis. 2011;doi:http://dx.doi.org/10.3201/eid1710.110117.

Issue: September 2011

New findings indicate the emergence of oseltamivir-resistant 2009 H1N1 virus in England and Scotland — particularly among immunocompromised patients.

Laurence Calatayud, MD,trainee of the European Program for Intervention Epidemiology Training at the Health Protection Agency – Center for Infections in London, and colleagues assessed the possible risk factors for the emergence of oseltamivir-resistant (Tamiflu, Roche) 2009 H1N1 in patients admitted to the hospital between Jan. 4, 2009, and April 30, 2010.

Of the 3,515 H1N1 specimens pooled from England and Scotland hospital laboratories, 36 (1%) were oseltamivir-resistant and 3,479 (99%) were oseltamivir-sensitive. All of the samples from primary care clinics were oseltamivir-sensitive, according to the researchers. Two patients were not admitted to the hospital and, therefore, not included in the analysis.

Of the 34 patients with oseltamivir-resistant H1N1 admitted to the hospital, 26.5% were from Scotland vs. 73.5% from England. The patients had a median age of 52 years; 67.6% were male.

Case-patients were nine times more likely than controls to have an underlying medical condition. Twenty-eight case-patients had one or more underlying conditions:

Immunocompromised (75%).
Chronic respiratory diseases (25%).
Diabetes (14.3%).
Chronic cardiac, liver or neurological disease (10.7%).
Morbidly obese (8%).

After researchers adjusted for age and gender, case-patients remained significantly more likely than controls to be immunocompromised and at a higher risk for development of respiratory complications (OR=18.1; 95% CI, 6.6-49.9).

Researchers said they recommend “testing for antiviral resistance to ensure appropriate antiviral prescribing and minimize the risk for treatment failure and person-to-person transmission of the resistant strain.”

Disclosure: The researchers report no relevant financial disclosures.

Thomas M. File Jr., MD

As prescribing clinicians, we are always concerned about emerging antimicrobial resistance and the impact this has on our ability to safely treat patients. This study documents cases of neuraminidase inhibitor-resistance for the epidemic 2009 H1N1 strain in England and Scotland from April 2009 through April 2010. The large majorities of resistant case-patients were immunocompromised and received prior antiviral agents. Of interest, all samples from primary care clinics were oseltamivir-susceptible. The rate of resistance in this study appears to be similar to the rate reported for the US by the CDC, which reported on 4,229 samples of 2009 H1N1 collected since Oct. 1, 2010, and found 39 (0.9%) resistant to oseltamivir. Of the isolates tested, none were resistant to zanamivir. See CDC’s Fluview for week ending May 21, 2011 (www.cdc.gov).

Resistance does sporadically emerge on treatment, most likely among immunocompromised patients and associated with antiviral therapy. Thus, as indicated in the paper by Calatayud and colleagues, we need to be vigilant about monitoring for rates of oseltamivir-resistance, especially among immunocompromised and those with prolonged symptoms and shedding of virus. This observation enhances the importance for accurate diagnosis utilizing molecular tests so we can be more definitive in prescribing to reduce unnecessary use (therefore, decrease the chance for selection of resistance). Of interest, this report indicates there has already been a change in antiviral recommendation in the UK to include increased use of zanamivir as monotherapy or combined with oseltamivir “for all immunocompromised patients.” I am not aware of similar recommendations in the US at the present time, and I question the rational for combination neuraminidase inhibitor treatment without good clinical trial data to support this recommendation. Finally, and from my perspective most importantly, this reinforces the need to emphasize influenza vaccination. It is certainly preferable to prevent influenza rather than rely on antiviral therapy for which resistance may be present.

– Thomas M. File Jr., MD

Infectious Diseases News Editorial Board member

Disclosure: Dr. File reports no relevant financial disclosures.

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