Early Neuraminidase Inhibitor Research Articles

Prognostic factors for the development of lower respiratory tract infection after influenza virus infection in allogeneic hematopoietic stem cell transplantation recipients: A Kanto Study Group for Cell Therapy multicenter analysis

ObjectivesInfluenza virus infection (IVI) occasionally causes lower respiratory tract infection (LRTI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the progression to LRTI entails a high mortality, the role of early antiviral therapy for its prevention has not been fully elucidated. MethodsThis was a multicenter retrospective study using an additional questionnaire. Allo-HSCT recipients who developed IVI between 2012 and 2020 were included. ResultsA total of 278 cases of IVI after allo-HSCT were identified from 15 institutions. The median patient age was 49 years, and the median time from allo-HSCT to IVI was 918 days. Neuraminidase inhibitors were administered within 48 hours of symptom onset (early neuraminidase inhibitor [NAI]) in 199 (76.9%) patients. Subsequently, 36 (12.3%) patients developed LRTI. On the multivariate analysis, age ≥50 years (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.02-4.58) and moderate to severe chronic graft-versus-host disease (HR, 2.28; 95% CI, 1.14-4.58) were significantly associated with progression to LRTI, whereas early NAI suppressed the progression (HR, 0.17; 95% CI, 0.06-0.46). The IVI-related mortality rate was 2.2%. ConclusionTo reduce the risk of LRTI development after IVI, early NAI therapy should be considered in allo-HSCT recipients, especially with older patients and those with chronic graft-versus-host disease.

Flu-IV score: a predictive tool for assessing the risk of invasive mechanical ventilation in patients with influenza-related pneumonia

BackgroundThe need for invasive mechanical ventilation (IMV) is linked to significant morbidity and mortality in patients with influenza-related pneumonia (Flu-p). We aimed to develop an assessment tool to predict IMV among Flu-p patients within 14 days of admission.MethodsIn total, 1107 Flu-p patients from five teaching hospitals were retrospectively enrolled from January 2012 to December 2019, including 895 patients in the derivation cohort and 212 patients in the validation cohort. The predictive model was established based on independent risk factors for IMV in the Flu-p patients from the derivation cohort.ResultsOverall, 10.6% (117/1107) of patients underwent IMV within 14 days of admission. Multivariate regression analyses revealed that the following factors were associated with IMV: early neuraminidase inhibitor use (− 3 points), lymphocytes < 0.8 × 109/L (1 point), multi-lobar infiltrates (1 point), systemic corticosteroid use (1 point), age ≥ 65 years old (1 points), PaO2/FiO2 < 300 mmHg (2 points), respiratory rate ≥ 30 breaths/min (3 points), and arterial PH < 7.35 (4 points). A total score of five points was used to identify patients at risk of IMV. This model had a sensitivity of 85.5%, a specificity of 88.8%, and exhibited better predictive performance than the ROX index (AUROC = 0.909 vs. 0.594, p = 0.004), modified ROX index (AUROC = 0.909 vs. 0.633, p = 0.012), and HACOR scale (AUROC = 0.909 vs. 0.622, p < 0.001) using the validation cohort.ConclusionsFlu-IV score is a valuable prediction rule for 14-day IMV rates in Flu-p patients. However, it should be validated in a prospective study before implementation.

Influenza Antiviral Therapy and Length of Hospitalization

Source: Campbell AP, Tokars JI, Reynolds S, et al. Influenza antiviral treatment and length of stay. Pediatrics. 2021;148(4):e2021050417; doi:10.1542/peds.2021-050417Investigators from multiple institutions conducted a retrospective study to assess the effect of treatment with neuraminidase inhibitors (NAIs) on length of hospital stay (LOS) in children with influenza. Study data were abstracted from the Influenza Hospitalization Surveillance Network (FluServ-NET), a population-based surveillance network with data from 10 counties in different states and 5 entire states. Information on patients in the surveillance system, including demographics, patient characteristics, treatment with NAIs, symptom onset, and details on hospitalization were collected. Study participants were children <18 years old with laboratory-identified influenza who were divided into 2 cohorts for analysis. Cohort 1 included children with ≥1 medical condition and not admitted or transferred to an ICU who were hospitalized during the 2012–2013 influenza season. Cohort 2 were children with or without an underlying medical condition who were admitted to an ICU during 3 consecutive influenza seasons (2010–2011, 2011–2012, and 2012–2013). Exclusion criteria included missing information on receipt of NAIs, LOS <1 day, and symptom onset on or after ≥3 days prior to admission. Receipt of NAIs was classified as never, ≤2 days after onset of symptoms (early), or ≥3 days after symptoms (late). The primary study outcome was LOS, and the association of treatment with NAIs on LOS was evaluated using Cox regression after controlling for confounders.During the 2012–2013 influenza season, data on 1,924 children hospitalized with influenza were collected in FluServ-NET; 1,039 (54%) had ≥1 underlying medical condition. After applying exclusions, cohort 1 consisted of 309 children, of whom 199 (64.4%) received early NAI ≤2 days after treatment, 37 (12.0%) were treated ≥3 days after symptom onset, and 73 (23.6%) had no treatment with NAIs. After controlling for confounders, a shorter LOS was statistically associated with early NAI treatment (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.05, 1.80), but not late treatment (HR, 1.02; 95% CI, 0.67, 1.54). There were 299 children admitted to an ICU, included in cohort 2 analyses, with a median LOS of 5 days. NAIs were started ≤2 days after symptom onset in 168 (56%), ≥3 days after onset of symptoms in 45 (15%), and never in 86 (29%). In this cohort, early NAI treatment also was associated with shorter LOS (HR, 1.46; 95% CI, 1.11, 1.92), and late NAI treatment was not (HR, 1.20; 95% CI, 0.85, 1.69).The authors conclude that early treatment with NAIs in children with influenza was associated with shorter hospitalizations.Dr Doolittle has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Treatment with NAIs has been shown to reduce hospitalization among high-risk adults and children with influenza.1 NAIs also have been shown to reduce mortality among hospitalized adults when given ≤2 days after symptom onset but have not been associated with a reduction in mortality among children <16 years.2 Because of these studies and others, treatment with NAIs has been recommended for patients of all ages with influenza since 2009.3 However, since most studies of NAIs were performed on outpatients and adults, the experience among hospitalized children is limited.4 The current investigators close that gap.The investigators employed a large data set, controlled for confounding variables, and were careful to reject participants for whom NAI use was not known. Further, they studied children who would benefit the most from NAIs: those with ≥1 chronic illness and those admitted to the ICU. The most common chronic medical conditions included chronic lung and cardiac diseases such as asthma, neurologic diseases, prematurity, immunocompromise, and chronic metabolic or blood disorders. Interestingly, 48% of the chronic illness cohort and 37% of the ICU cohort were vaccinated for influenza. Vaccination status was not associated with LOS.The results of the current study affirm the Centers for Disease Control and Prevention (CDC) position to start early empiric treatment with NAIs on all patients suspected of influenza.3 Interestingly, the CDC also recommends NAIs in all hospitalized patients with influenza regardless of time of onset due to potential reduction in viral shedding and LOS.5Among children with influenza admitted to the ICU or with ≥1 chronic conditions, treatment with NAIs within ≤2 days of symptom onset is associated with a shorter LOS compared to those treated ≥3 days after symptom onset or not at all. (See AAP Grand Rounds. 2021;46[4]:39).6

The severity and risk factors for mortality in immunocompromised adult patients hospitalized with influenza-related pneumonia

ObjectiveTo explore disease severity and risk factors for 30-day mortality of adult immunocompromised (IC) patients hospitalized with influenza-related pneumonia (Flu-p).MethodA total of 122 IC and 1191 immunocompetent patients hospitalized with Flu-p from January 2012 to December 2018 were recruited retrospectively from five teaching hospitals in China.ResultsAfter controlling for confounders, multivariate logistic regression analysis showed that immunosuppression was associated with increased risks for invasive ventilation [odds ratio: (OR) 2.475, 95% confidence interval (CI): 1.511–4.053, p < 0.001], admittance to the intensive care unit (OR: 3.247, 95% CI 2.064–5.106, p < 0.001), and 30-day mortality (OR: 3.206, 95% CI 1.926–5.335, p < 0.001) in patients with Flu-p. Another multivariate logistic regression model revealed that baseline lymphocyte counts (OR: 0.993, 95% CI 0.990–0.996, p < 0.001), coinfection (OR: 5.450, 95% CI 1.638–18.167, p = 0.006), early neuraminidase inhibitor therapy (OR 0.401, 95% CI 0.127–0.878, p = 0.001), and systemic corticosteroid use at admission (OR: 6.414, 95% CI 1.348–30.512, p = 0.020) were independently related to 30-day mortality in IC patients with Flu-p. Based on analysis of the receiver operating characteristic curve (ROC), the optimal cutoff for lymphocyte counts was 0.6 × 109/L [area under the ROC (AUROC) = 0.824, 95% CI 0.744—0.887], sensitivity: 97.8%, specificity: 73.7%].ConclusionsIC conditions are associated with more severe outcomes in patients with Flu-p. The predictors for mortality that we identified may be valuable for the management of Flu-p among IC patients.

Complications of Cardiovascular Events in Patients Hospitalized with Influenza-Related Pneumonia.

PurposeInfluenza virus infections are a key cause of community-acquired pneumonia (CAP). Cardiovascular events (CVEs) are common among CAP and influenza patients, but there have been few population-based studies of influenza-related pneumonia (Flu-p) patients published to date.MethodsA retrospective analysis of 1191 immunocompetent hospitalized adult Flu-p patients from January 2012 to December 2018 in five teaching hospitals in China was conducted.ResultsA total of 24.6% (293/1191) of patients developed at least one form of CVE-related complication while hospitalized. In a multivariate logistic regression analysis, hypertension, cerebrovascular disease, coronary artery disease, preexisting heart failure, systolic blood pressure <90 mmHg, respiratory rates ≥30 breaths/min, a lymphocyte count <0.8×109/L, PaO2/FiO2 <300 mmHg, and systemic corticosteroid administration were independently associated with the incidence of CVEs; while early neuraminidase inhibitor treatment and angiotensin converting enzyme inhibitors/angiotensin II receptor blocker treatment were associated with a lower risk of CVEs. After controlling for potential confounding variables, we determined that CVEs were linked to a higher risk of 30-day mortality (OR 3.307, 95% CI 2.198–4.975, p < 0.001) in Flu-p patients.ConclusionCVE-related complications are common among hospitalized Flu-p patients and are associated with negative patient outcomes. Clarifying these CVE-related risk factors can aid in their clinical prevention and management.

1505. Antiviral and Antibiotic Prescribing Among Patients at an Ambulatory Cancer Center with Laboratory-Confirmed Influenza

BackgroundCancer patients are at high risk for serious complications due to influenza. Early treatment with neuraminidase inhibitors (NAIs) is recommended for high-risk patients with suspected or documented influenza. Limited data exist on timing of presentation to care and ambulatory management of cancer patients with influenza. We sought to characterize antimicrobial prescribing and outcomes among patients with influenza at a large cancer center.MethodsWe selected consecutive patients seen in the ambulatory cancer clinic with laboratory confirmed influenza between January 1, 2016 and December 31, 2018 for chart review. A lab-developed multiplex PCR assay was used with a turnaround time of about 24 hours. We obtained demographics, symptoms at first clinic encounter (day 0), viral testing, NAI and antibiotic prescribing, and clinical outcomes.ResultsOf 138 charts reviewed, 133 (96%) were eligible for analysis. 109 (82%) had an underlying hematologic malignancy. 84 (63%) tested positive for influenza A and 49 for influenza B. 58 (44%) presented to care within 48 hours of symptom onset (F1). The most commonly reported symptoms were cough (83%), fever (41%), and rhinorrhea (40%) (F2). 110 (83%) were prescribed oseltamivir, with 24 (22%) receiving empiric therapy on day 0, and 63 (57%) prescribed on day 1 (F3). Among 109 patients with known symptom onset date, 34 (31%) were prescribed oseltamivir within 48 hours of symptom onset. 23 (17.3%) were prescribed antibiotics, 17 (74%) on day 0 (F3). Levofloxacin (26%), azithromycin (21%) and vancomycin (18%) were most commonly prescribed. Nine (6.8%) patients progressed to lower respiratory tract infection, 1 complicated by bacterial pneumonia. There were 11 (8.3%) influenza-related hospitalizations, 1 (0.7%) ICU admission, and no influenza-related deaths.Figure 1. Time From Symptom Onset to Date of First Clinical Encounter Figure 2. Symptoms Reported at First Clinical Encounter Figure 3. Time from First Clinical Encounter to Oseltamivir and Antibiotic Prescription ConclusionNAIs were frequently prescribed among cancer patients, but less than a third received treatment within 48 hours of symptom onset. Most were prescribed NAIs only after test results were available, while antibiotics were prescribed empirically. Delayed presentation to care is an obstacle to early NAI use; patient and provider education along with rapid diagnostics are needed to improve early NAI use among cancer patients with influenza.Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

Invasive pulmonary aspergillosis in immunocompetent patients hospitalised with influenza A-related pneumonia: a multicenter retrospective study

BackgroundIncreasing cases of pulmonary aspergillosis (IPA) in immunocompetent patients with severe influenza have been reported. Howevere, the risk factors for occurence and death are largely unknown.MethodsData of hospitalised patients with influenza A-related pneumonia (FluA-p) obtained from five teaching hospitals from 2031 to 2018, were reviewed. Univariate and multivariate logistical regression analyses were performed to determine the risk factors involved in the acquisition and 60-day mortality in IPA patients.ResultsOf the 693 FluA-p patients included in the study, 3.0% (21/693) were IPA patients with a 60-day mortality of 42.9% (9/21). Adjusted for confounders, a Cox proportional hazard model showed that IPA was associated with increased risk for 60-day mortality [hazard ratio (HR) 4.336, 95% confidence interval (CI) 1.191–15.784, p = 0.026] in FluA-p patients. A multivariate logistic regression model confirmed that age (odd ratio (OR) 1.147, 95% CI 1.048–1.225, p = 0.003), systemic corticosteroids use before IPA diagnosis (OR 33.773, 95% CI 5.681–76.764, p < 0.001), leukocytes > 10 × 109/L (OR 1.988, 95% CI 1.028–6.454, p = 0.029) and lymphocytes < 0.8 × 109/L on admission (OR 34.813, 95% CI 1.676–73.006, p = 0.022), were related with the acquisition of IPA. Early neuraminidase inhibitor use (OR 0.290, 95% CI 0.002–0.584, p = 0.021) was associated with a decreased risk for a 60-day mortality in IPA patients.ConclusionsOur results showed that IPA worsen the clinical outcomes of FluA-p patients. The risk factors for the acquisition and death were helpful for the clinicians in preventing and treating IPA.

The impact of early neuraminidase inhibitor therapy on clinical outcomes in patients hospitalised with influenza A-related pneumonia: a multicenter, retrospective study

BackgroundGuidelines emphasize prompt antiviral treatment in severe influenza patients. Although nearly a 50% of severe influenza present with pneumonia, the effect of early (≤ 2 days after illness onset) neuraminidase inhibitor (NAI) use on the clinical outcomes of influenza A-related pneumonia (FluA-p) has rarely been assessed. Furthermore, data about the administration of NAIs in the real-world management of Flu-p in China are limited.MethodsData of patients hospitalised with FluA-p from five teaching hospitals in China from 1 January 2013 to 31 December 2018 were reviewed retrospectively. The impact of early NAI therapy on the outcomes in FluA-p patients, and the indications of early NAI administration by clinicians were evaluated by logistic regression analysis.ResultsIn total, 693 FluA-p patients were included. Of these patients, 33.5% (232/693) were treated early. After adjusting for weighted propensity scores for treatment, systemic corticosteroid and antibiotic use, a multivariate logistic regression model showed that early NAI therapy was associated with decreased risk for invasive ventilation [odds ratio (OR) 0.511, 95% confidence interval (CI) 0.312–0.835, p = 0.007) and 30-day mortality (OR 0.533, 95% CI 0.210–0.807, p < 0.001) in FluA-p patients. A multivariate logistic regression model confirmed early NAI use (OR 0.415, 95% CI 0.195–0.858, p = 0.001) was a predictor for 30-day mortality in FluA-p patients and a positive rapid influenza diagnostic test was the only indication (OR 3.586, 95% CI 1.259–10.219, p < 0.001) related to the prescription of early NAI by clinicians.ConclusionsEarly NAI therapy is associated with better outcomes in FluA-p patients. Improved education and training of clinicians on the guidelines of influenza are needed.

Impact of early neuraminidase inhibitor treatment on clinical outcomes in patients with influenza B-related pneumonia: a multicenter cohort study.

The aim of this study is to evaluate the impact of early (within 2days after disease onset) neuraminidase inhibitor (NAI) administration on clinical outcomes in patients with laboratory-confirmed influenza B-related pneumonia (FluB-p). This was a multicenter study conducted from 1 January 2013 to 1 May 2019. Data of immunocompetent adult and adolescent FluB-p patients hospitalized at five different teaching hospitals in China were retrospectively collected, including demographic and clinical features as well as clinical and treatment outcomes. Univariate and multivariate logistic regression analyses were performed to assess the effects of early NAI administration on clinical outcomes in FluB-p patients. In total, 386 hospitalized patients with community-onset FluB-p were included in this study, of whom 39.6% (153/386) were treated with NAI early. After adjusting for the weighted propensity scores of treatment, systemic corticosteroid, and antibiotic uses, the results of multivariate logistic regression model indicated that early NAI treatment was associated with the decreased risks of invasive ventilation [odd ratio (OR) 0.325, 95% confidence interval (CI) 0.123-0.858; p = 0.023), admittance to intensive care unit (OR 0.425, 95% CI 0.204-0.882; p = 0.022), and 30-day mortality (OR 0.416, 95% CI 0.184-0.944, p = 0.036)] in FluB-p patients. In addition, the multivariate logistic regression analysis revealed that early NAI treatment (OR 0.306, 95% CI 0.063-0.618; p = 0.010) was an independent predictor for 30-day mortality in patients with FluB-p. Early NAI treatment was associated with better clinical outcomes in FluB-p patients, which supports the recommendations of its use in severe influenza illness.

Molecular Point-of-care Testing for Influenza to Improve Early Neuraminidase Inhibitor Treatment and Outcomes in Hospitalized Adults

Molecular Point-of-care Testing for Influenza to Improve Early Neuraminidase Inhibitor Treatment and Outcomes in Hospitalized Adults

Early Oseltamivir After Hospital Admission Is Associated With Shortened Hospitalization: A 5-Year Analysis of Oseltamivir Timing and Clinical Outcomes.

Neuraminidase inhibitors (NAIs) are the only effective therapy for influenza, but few studies have assessed the impact of early NAI therapy on clinical outcomes or the patient-level factors that determine early NAI delivery in hospitalized patients. We conducted a retrospective cohort study of all adults hospitalized in a metropolitan tertiary care hospital with confirmed influenza from April 2009 to March 2014. We performed logistic regression to determine patient-level factors that were associated with early NAI therapy. We analyzed the association of early NAI therapy with hospital lengths of stay (LOS) and in-hospital mortality rates using linear and logistic regression, respectively. In total, 699 patients were admitted with influenza during the 5 influenza seasons. Of those, 582 (83.4%) received NAI therapy; however, only 26.0% received the first dose within 6 hours of hospitalization (early NAI). Patients with diabetes mellitus or pregnancy were more likely to receive early NAI (P = .01, vs. P < .001 in those without these conditions), as were those reporting fever or myalgias at presentation (P = .002, vs. P = .005 without). Immunosuppressed patients were less likely to receive early NAI (P = .04). Early NAI was associated with shorter hospital LOS (P < .001). No patients died in the early NAI group, compared to 18 deaths in the 399 patients receiving NAI after 6 hours (4.5%) and 4 deaths in the 116 patients not receiving NAI (3.4%). Over multiple influenza seasons, early NAI therapy was associated with shorter LOS in patients admitted with influenza. This suggests that efforts should focus on facilitating earlier therapy in patients with suspected influenza.

Late diagnosis of influenza in adult patients during a seasonal outbreak.

Background/AimsDue to advances in diagnostic techniques, clinicians are more frequently performing influenza diagnostic tests and referring to their test results ahead of the administration of neuraminidase inhibitors (NAIs). To investigate the clinical significance of the time from symptom onset to laboratory diagnosis, we reviewed the clinical characteristics of adult patients with influenza who had an early laboratory diagnosis (ED) or a late laboratory diagnosis (LD) at one of four tertiary care centers during a seasonal outbreak of influenza.MethodsClinical data were collected from 1,405 adults during the 2013 to 2014 influenza season. A patient was regarded as receiving an ED or LD if he/she received an influenza diagnostic test at 0 to 1 or 4 to 7 days after symptom onset, respectively. Early NAI therapy and late NAI therapy were defined as the administration of NAI ≤ 2 or > 2 days after symptom onset, respectively.ResultsNearly half of the patients (47.0%) received an ED (n = 661), whereas 13.5% (n = 190) received a LD. Patients with a LD had initial symptoms of cough, sputum production, and dyspnea and experienced pneumonia, antibiotic therapy, hospitalization, and admission to the intensive care unit more often than those with an ED. NAI therapy and early NAI therapy were less frequent in patients with a LD than those with an ED. Of the analyzed baseline characteristics, age ≥ 50 years, influenza B infection, and diagnosis using a polymerase chain reaction test were significantly associated with a LD.ConclusionsLD was associated with inappropriate antiviral therapy and complicated presenting features in adult patients with seasonal influenza. ED of influenza should be emphasized, especially for older adults.

Benefit of Early Initiation of Neuraminidase Inhibitor Treatment to Hospitalized Patients With Avian Influenza A(H7N9) Virus.

The significance of early neuraminidase inhibitor (NAI) therapy for treating influenza A(H7N9) is currently unknown. The duration of viral shedding was monitored by reverse-transcription polymerase chain reaction after patients with confirmed H7N9 infection were admitted to the First Affiliated Hospital, Zhejiang University, during April 2013-April 2017. Indices such as the length of hospitalization and mortality were collected, and the correlation between the time of administration of NAI and the severity of disease was systematically analyzed. One hundred sixty patients with confirmed H7N9 infection were divided into 3 groups according to NAI starting time. Three of 20 (15%) patients for whom NAI was administered within 2 days died compared with 12 of 52 (23.1%) patients who received treatment within 2-5 days and 33 of 88 (37.5%) patients who were treated after 5 days (P < .05). The median durations of viral shedding from NAI therapy initiation was 4.5 days (interquartile range [IQR], 3-9 days) for patients who took antiviral medication within 2 days, which was significantly different from that for patients who took medication within 2-5 days (7.5 days [IQR, 4.25-12.75 days]) or after 5 days (7 days [IQR, 5-10 days]) (P < .05). We found that the duration of viral shedding from NAI therapy was the shortest in spring 2013 (5.5 days) and the longest in winter-spring 2016-2017 (8.5 days) (P < .05), showing a prolonged trend. Early NAI therapy within 2 days of illness shortened the duration of viral shedding and improved survival in patients with H7N9 viral infection.

Early administration of neuraminidase inhibitors in adult patients hospitalized for influenza does not benefit survival: a retrospective cohort study

The administration of neuraminidase inhibitors (NAIs) within 2days after the onset of symptoms (early NAI therapy) has been shown to reduce mortality in adult patients with severe influenza. However, there is no sufficiently solid evidence supporting the effectiveness of early NAI therapy on mortality. We reviewed the clinical data from 506 adult patients who were hospitalized for influenza between March 2010 and March 2014, to investigate the impact of early NAI therapy on mortality. Nearly one-third of the study patients were infected with influenza B (influenza A, influenza B, and co-infection of both in 68.8%, 28.1%, and 3.2%, respectively), and were diagnosed using the polymerase chain reaction (PCR) method (33.6%). Less than half (233, 46.0%) had received early NAI therapy. Patients with early NAI therapy were admitted to the hospital earlier, more frequently infected with influenza A, and more frequently diagnosed using rapid influenza detection tests compared to those without early NAI therapy. Although patients without early NAI therapy presented with more serious clinical manifestations, such as an initial symptom of dyspnea, pneumonia, and intensive care unit admission, than those with early NAI therapy, the in-hospital mortality of the former (2.9%, 8/273) did not differ from that of the latter (3.4%, 8/233) (p=0.75). We did not find a reduction in mortality associated with early NAI therapy in adult patients hospitalized for influenza. Further clinical studies including a large number of influenza B-infected patients with virus identification using PCR methodology rather than viral culture may be required to confirm the beneficial impact of early NAI therapy on mortality.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BackgroundThe impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.MethodsA worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids.ResultsOf 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)].ConclusionsEarly NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

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.

Very low pandemic influenza A (H1N1) 2009 mortality associated with early neuraminidase inhibitor treatment in Japan: Analysis of 1000 hospitalized children

There were many cases of pandemic influenza A (H1N1) 2009 (H1N1/09) in Japan during the 2009-2010 epidemic. They accounted for 16% of the total population (20.7 million/128 million), and 59% of the patients were children 15 years of age and under (12.2 million/20.7million). However, there were only 38 paediatric deaths. We analyzed the clinical manifestations and treatment of children hospitalized because of H1N1/09 infection in order to clarify the association between treatment with neuraminidase inhibitors and the low mortality rate. A retrospective chart review was performed on a total of 1000 paediatric inpatients. The causes of the hospitalizations were respiratory complications in 651 cases (65.1%), neurological complications in 255 cases (25.5%) and other complications in 94 cases. Neuraminidase inhibitors, primarily oseltamivir, had been used to treat 984 (98.4%) of the 1000 patients, and in 88.9% of the patients, treatment with neuraminidase inhibitors was initiated within 48 h after the onset of illness. Only 12 (1.2%) of the 1000 patients underwent mechanical ventilation, and one patient died of H1N1/09 infection. Although a high proportion of the patients in this study had severe respiratory complications, the case fatality rate was only 0.1%. The low mortality rate of children due to the H1N1/09 epidemic in Japan was probably attributable to the universal implementation of early treatment with neuraminidase inhibitors.