Use of Neuraminidase Inhibitors in Patients with 2009 Pandemic Influenza (H1n1)

Summary

One study 1 collected data on patients hospitalized with 2009 H1N1 influenza in the United States (n=272). Of the patients, 45% were <18 years and 5% were HASH(0x2fcfe80)65 years; 73% had at least one underlying medical condition (asthma, diabetes, heart, lung, or neurologic diseases, or pregnancy); 25% were admitted to an intensive care unit and 7% died. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness; 39% of patients received antiviral therapy within 48 hours after the onset of symptoms. Of the patients that were admitted to intensive care unit (ICU), 86% received antiviral drugs, and the median time from the onset of illness to the initiation of antiviral therapy was 6 days; 23% of patients received antiviral drugs within 48 hours after the onset of illness. Of the 19 patients who died, 90% received antiviral drugs, and the median time from the onset of illness to the initiation of antiviral therapy was 8 days; none of the patients who died received antiviral therapy within 48 hours after the onset of symptoms. In a multivariable model, the only variable that was significantly associated with a positive outcome was the receipt of antiviral drugs within 2 days after the onset of illness.

Another study 2 included reports on 788 pregnant women in the United States with 2009 influenza A(H1N1). Among those, 30 died. Among 509 hospitalized women, 22.6% were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU (56.9% vs 9.4%; RR 6.0, 95% CI 3.5 to 10.6) than those treated within 2 days after symptom onset. Only 1 death occurred in a patient who received treatment within 2 days of symptom onset.

A cumulative case-control study 3 included all laboratory-confirmed cases of pandemic H1N1 influenza among residents of the province of Manitoba, Canada, for whom the final location of treatment was known (n=795). The median interval from onset of symptoms to initiation of antiviral therapy was 2 days (interquartile range, IQR 1-3) for community cases, 4 days (IQR 2-6) for patients admitted to hospital and 6 days (IQR 4-9) for those admitted to an ICU (p<0.001). In a multivariable logistic model, the interval from onset of symptoms to initiation of antiviral therapy (OR 8.24, 95% CI 2.82 to 24.1), First Nations ethnicity (OR 6.52, 95% CI 2.04 to 0.8) and presence of an underlying comorbidity (OR 3.19, 95% CI 1.07 to 9.52) were associated with increased odds of admission to the ICU (i.e., severe disease) relative to community cases.

An observational study 4 from Mexico included 899 patients admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Critical illness occurred in 58 of 899 patients (6.5%). Patients were young (median 44, range 10 to 83 years), few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median 1 day, IQR 0 to 3 days), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia. By 60 days, 24 patients had died (41.4%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (OR 8.5, 95% CI 1.2 to 62.8).