Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008–2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19–0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52–3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23–0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12–0.32), but there was benefit with treatment within 3–5 days (adjusted HR 0.35, 95% CI 0.21–0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27–0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14–2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered. NAI treatment, secondary infections and corticosteroids may impact on survival of hospitalised influenza patients http://ow.ly/ErOsT

[1]  C. Del Mar,et al.  Statistical and methodological concerns about the beneficial effect of neuraminidase inhibitors on mortality. , 2014, The Lancet. Respiratory medicine.

[2]  J. Leonardi-Bee,et al.  Statistical and methodological concerns about the beneficial effect of neuraminidase inhibitors on mortality. , 2014, The Lancet. Respiratory medicine.

[3]  I. Douglas,et al.  Rosuvastatin for sepsis-associated acute respiratory distress syndrome. , 2014, The New England journal of medicine.

[4]  Gokhan Metan,et al.  Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. , 2014, The Lancet. Respiratory medicine.

[5]  J. McCullers.  The co-pathogenesis of influenza viruses with bacteria in the lung , 2014, Nature Reviews Microbiology.

[6]  T. Uyeki.  Preventing and controlling influenza with available interventions. , 2014, The New England journal of medicine.

[7]  Alicia M Fry,et al.  Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. , 2014, The Lancet. Infectious diseases.

[8]  B. Cao,et al.  Influenza pneumonia among adolescents and adults: a concurrent comparison between influenza A (H1N1) pdm09 and A (H3N2) in the post-pandemic period , 2013, The clinical respiratory journal.

[9]  D. Fedson.  Treating influenza with statins and other immunomodulatory agents. , 2013, Antiviral research.

[10]  P. Yang,et al.  Influenza vaccination coverage rates among adults before and after the 2009 influenza pandemic and the reasons for non-vaccination in Beijing, China: A cross-sectional study , 2013, BMC Public Health.

[11]  T. Tumpey,et al.  Simvastatin and oseltamivir combination therapy does not improve the effectiveness of oseltamivir alone following highly pathogenic avian H5N1 influenza virus infection in mice. , 2013, Virology.

[12]  D. Hui,et al.  Adjunctive therapies and immunomodulatory agents in the management of severe influenza , 2013, Antiviral Research.

[13]  Dayan Wang,et al.  Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals , 2013, Nature Communications.

[14]  R. Bellomo,et al.  A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. , 2013, American journal of respiratory and critical care medicine.

[15]  G. Lui,et al.  Comparisons of oseltamivir‐resistant (H275Y) and concurrent oseltamivir‐susceptible seasonal influenza A(H1N1) virus infections in hospitalized adults, 2008–2009 , 2012, Influenza and other respiratory viruses.

[16]  M. Fine,et al.  Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumonia-related outcomes. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  N. Dreyer,et al.  Determinants of antiviral effectiveness in influenza virus A subtype H5N1. , 2012, The Journal of infectious diseases.

[18]  Robert Schechter,et al.  Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  A. Coleman.  Antivirals for Treatment of Influenza: A Systematic Review and Meta-Analysis of Observational Studies , 2012 .

[20]  P. Horby,et al.  Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. , 2012, The Lancet. Infectious diseases.

[21]  W. Schaffner,et al.  Reduced influenza antiviral treatment among children and adults hospitalized with laboratory-confirmed influenza infection in the year after the 2009 pandemic. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  R. Xu,et al.  Assessing the effect of vaccine on spontaneous abortion using time‐dependent covariates Cox models , 2012, Pharmacoepidemiology and drug safety.

[23]  S. Tsui.  Some observations on the evolution and new improvement of Chinese guidelines for diagnosis and treatment of influenza. , 2012, Journal of thoracic disease.

[24]  Yonghong Xiao,et al.  Antiviral Therapy and Outcomes of Patients with Pneumonia Caused by Influenza A Pandemic (H1N1) Virus , 2012, PloS one.

[25]  M. Ison,et al.  Diagnosis, management and outcomes of adults hospitalized with influenza. , 2012, Antiviral therapy.

[26]  E. Walsh.  Statins and influenza: can we move forward? , 2012, The Journal of infectious diseases.

[27]  W. Schaffner,et al.  Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. , 2012, The Journal of infectious diseases.

[28]  N. Zhong,et al.  Chinese guidelines for diagnosis and treatment of influenza (2011). , 2011, Journal of thoracic disease.

[29]  E. Picard,et al.  Dexamethasone in community-acquired pneumonia , 2011, The Lancet.

[30]  R. Lin,et al.  Influenza disease burden in adults by subtypes following the initial epidemic of pandemic H1N1 in Singapore , 2011, Influenza and other respiratory viruses.

[31]  Zijian Feng,et al.  Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1 infection. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  J. R. Pérez Padilla,et al.  Reducing Occurrence and Severity of Pneumonia Due to Pandemic H1N1 2009 by Early Oseltamivir Administration: A Retrospective Study in Mexico , 2011, PloS one.

[33]  D. Hui,et al.  Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza? , 2011, The Journal of infectious diseases.

[34]  S. Yun,et al.  Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. , 2011, American journal of respiratory and critical care medicine.

[35]  B. Cao,et al.  Clinical Features of Pneumonia Caused by 2009 Influenza A(H1N1) Virus in Beijing, China , 2011, Chest.

[36]  Weizhong Yang,et al.  Risk factors for severe illness with 2009 pandemic influenza A (H1N1) virus infection in China. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[37]  L. Gubareva,et al.  Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). , 2011, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[38]  L. Grohskopf,et al.  Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). , 2011, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[39]  N. Dreyer,et al.  Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. , 2010, The Journal of infectious diseases.

[40]  F. Moura,et al.  Influenza in the tropics , 2010, Current opinion in infectious diseases.

[41]  T. Rebmann,et al.  Preventing ventilator-associated pneumonia: An executive summary of the Association for Professionals in Infection Control and Epidemiology, Inc, Elimination Guide. , 2010, American journal of infection control.

[42]  J. Sung,et al.  Outcomes of adults hospitalised with severe influenza , 2010, Thorax.

[43]  Y. Leo,et al.  Effects of early oseltamivir therapy on viral shedding in 2009 pandemic influenza A (H1N1) virus infection. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[44]  Y. Leo,et al.  Pandemic (H1N1) 2009 Surveillance and Prevalence of Seasonal Influenza, Singapore , 2010, Emerging infectious diseases.

[45]  Timothy H Rainer,et al.  Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys , 2009, BMJ : British Medical Journal.

[46]  J. Sung,et al.  Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza , 2009, The Journal of infectious diseases.