Reducing Occurrence and Severity of Pneumonia Due to Pandemic H1N1 2009 by Early Oseltamivir Administration: A Retrospective Study in Mexico

Abstract

BackgroundAnti-viral treatment has been used to treat severe or progressive illness due to pandemic H1N1 2009. A main cause of severe illness in pandemic H1N1 2009 is viral pneumonia; however, it is unclear how effective antiviral treatment is against pneumonia when administered >48 hours after symptom onset. Therefore, we aimed to determine how time from symptom onset to antiviral administration affected the effectiveness of antiviral treatment against pneumonia due to pandemic (H1N1) 2009.Methods/Principal FindingsA retrospective medical chart review of 442 patients was conducted in a hospital in Mexico. Subjects had tested positive for pandemic H1N1 2009 virus by real-time reverse-transcriptase-polymerase-chain-reaction and were administered oseltamivir. Median time from symptom onset to oseltamivir administration was 5.0 days (range, 0–43). 442 subjects, 71 (16.1%) had severe pneumonia which required mechanical ventilation, 191 (43.2%) had mild to moderate pneumonia, and 180 (40%) did not have pneumonia. Subjects were divided into four groups based on time to oseltamivir administration: ≤2, 3–7, 8–14, and >14 days. Severity of respiratory features was associated with time to treatment, and multivariate analysis indicated that time to oseltamivir administration was associated with severity of respiratory features. A proportional odds model indicated that 50% probability for occurrence of pneumonia of any severity and that of severe pneumonia in patients who would develop pneumonia reached at approximately 3.4 and 21 days, respectively, after symptom onset. Patients with a shorter time to oseltamivir administration were discharged earlier from the hospital.ConclusionsEarlier initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic H1N1 2009. Even when administered >48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia. Application of these results would benefit patients affected by future influenza pandemics.

Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009–2010 H1N1 pandemic: summary of an ecological study

“…Limitations aside, this analysis demonstrates an association between NAI supply and H1N1 mortality during the 2009 influenza pandemic at an ecological level consistent with other findings on the individual level 3, 10, 14. This effect does not seem large on a population level and equates to a drop in mortality in the Americas from the observed 1·18 per 100 000 to 1·16 per 100 000 for a 10% increase kg of oseltamivir/100 000.…”

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

“…Individual observational studies during the 2009–2010 pandemic suggest a possible benefit of NAIs in reducing pneumonia incidence, but are limited by small sample sizes 13, 14, 15, 16. A meta‐analysis of 2009–2010 pandemic data from patients hospitalised with influenza A(H1N1)pdm09 virus infection reported that early treatment with NAIs reduced the likelihood of IRP compared to late treatment by 65% 17.…”

Randomised controlled trial and health economic evaluation of the impact of diagnostic testing for influenza, respiratory syncytial virus and Streptococcus pneumoniae infection on the management of acute admissions in the elderly and high-risk 18- to 64-year-olds

“…However, we did not stratify illness severity as part of the study or take into consideration the possibility that late treatment may benefit severely ill patients who are hospitalised with influenza, as such treatment falls outside NICE guidance. Evidence indicates that oseltamivir (Tamiflu ® , Roche) treatment of patients hospitalised with seasonal [71][72][73] and pandemic 2009 H1N1 influenza [74][75][76][77][78][79][80] is associated with reductions in radiological pneumonia, illness severity and death. Even when administered > 48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia due to 2009 pandemic H1N1 virus.…”

“…Even when administered > 48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia due to 2009 pandemic H1N1 virus. 79 Survival benefits for H5N1 influenza have also been observed when treatment with oseltamivir was delayed up to 6 days after symptom onset. 81 l Second, the ability to diagnose influenza is dependent on the sensitivity of the test.…”