Chest

Chest

Volume 140, Issue 4, October 2011, Pages 1025-1032
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Original Research
Chest Infections
Timing of Oseltamivir Administration and Outcomes in Hospitalized Adults With Pandemic 2009 Influenza A(H1N1) Virus Infection

https://doi.org/10.1378/chest.10-2792Get rights and content

Background

Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) virus infection are scarce. We aimed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1).

Methods

Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable. Outcomes were duration of fever, hospital length of stay (LOS), need for mechanical ventilation, and mortality during hospitalization. Multivariate logistic regression was used to describe the association between the independent variable and the outcomes.

Results

Five hundred thirty-eight hospitalized patients with A(H1N1) were studied. The median time from onset of symptoms to oseltamivir administration was 3 days (interquartile range [IQR], 2-5 days). With regard to outcomes, the median duration of fever was 2 days (IQR, 1-3 days), the median LOS was 5 days (IQR, 3-8 days), 49 patients (9.1%) underwent mechanical ventilation, and 11 patients (2%) died during hospitalization. In univariate analysis, prolonged duration of fever (above the median), prolonged LOS (above the median), need for mechanical ventilation, and mortality all increased with time to oseltamivir administration (χ2 test for trend P = .001, P ≤ .001, P = .008, and P = .001, respectively). After adjustment for confounding factors, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was associated with a prolonged duration of fever (OR, 1.10; 95% CI, 1.02-1.19), prolonged LOS (OR, 1.07; 95% CI, 1.00-1.15), and higher mortality (OR, 1.20; 95% CI, 1.06-1.35).

Conclusions

Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1), even in those who are admitted beyond 48 h after onset of symptoms.

Section snippets

Study Design and Study Population

This observational analysis was of a prospective cohort of adults aged > 15 years hospitalized with confirmed A(H1N1) virus infection at 13 Spanish university hospitals between June 12, 2009, and November 10, 2009. All patients had an influenza-like illness with laboratory-confirmed A(H1N1) virus infection by real-time reverse-transcription polymerase chain reaction (RT-PCR) or viral culture.16 Cases were identified at the ED by attending physicians or investigators when the microbiology

Patient Characteristics

Of the 585 hospitalized patients with laboratory-confirmed A(H1N1), 47 with missing data on time from symptom onset to oseltamivir administration were excluded. Excluded patients did not present significant differences with regard to age, signs and symptoms, and outcomes compared with patients included in the study. Among the 538 patients analyzed in the present study, the median time from onset of symptoms to hospital arrival was 3 days (IQR, 2-5 days). The median age was 39 years (IQR, 28-52

Discussion

In this large, prospective cohort study of hospitalized patients with laboratory-confirmed A(H1N1) virus infection, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was independently associated with a prolonged duration of the fever, prolonged LOS, and higher mortality during hospitalization. Moreover, we performed a subgroup analysis in patients with progressive, severe, or complicated illness at hospital admission because hospital criteria decisions were not

Conclusions

The results of this study suggest that timely oseltamivir administration has a beneficial impact on duration of fever, LOS, need for mechanical ventilation, and mortality in hospitalized patients with A(H1N1) virus infection. Consequently, treatment with oseltamivir should be administered as soon as possible to improve the clinical outcomes, even in patients who seek medical advice at a relatively late stage in the course of the illness.

Acknowledgments

Author contributions: Drs Viasus and Carratalà had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Viasus: contributed to the protocol design, data collection and analysis, writing and final approval of the manuscript.

Dr Paño-Pardo: contributed to data collection and analysis and review and final approval of the manuscript.

Dr Pachón: contributed to obtaining funding, data collection, and review and final

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    • Cited by (0)

    Funding/Support: This study was supported by Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, Programa de Investigación sobre gripe A/H1N1 (grant GR09/0014), and Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III. It was cofinanced by the European Regional Development Fund “A way to achieve Europe,” Spanish Network for Research in Infectious Diseases (REIPI RD06/0008). Dr Viasus is the recipient of a research grant from the Institut d'Investigació Biomèdica de Bellvitge (IDIBELL).

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

    1

    A list of the study group members is available in e-Appendix 1.

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    Copyright © 2011 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.