In mild to moderate uncomplicated disease, the reported benefits of early treatment (< 48 h of symptom onset) with NI have been a shorter duration and severity of flu-like symptoms, and a reduced duration of viral shedding [46] [47] [48] [49] . More importantly, several trials and a few systematic reviews have shown that treatment with NI may reduce illness severity and the rate of lower respiratory tract complications [47, [50] [51] [52] . In a meta-analysis of 10 randomizedcontrolled trials, Kaiser et al. found that therapy with oseltamivir was effective in reducing the incidence of influenzarelated lower respiratory tract complications that required antibiotic use (4.6 % for oseltamivir vs. 10.3 % for placebo, P<0.001), independent of the presence of risk factors for complications [51] . More recently, Hernán et al. conducted another meta-analysis of 11 controlled trials, most of which were included in the previous meta-analysis by Kaiser et al. They found that treatment with oseltamivir significantly reduced influenza-related lower respiratory tract complications by 37 % (CI 95 % ) [52] . NI have also been reported to reduce the duration of hospitalization in severely-ill cases [53] , and also to reduce influenza-related mortality [54] . During the 2009 H1N1 Influenza A pandemic, several observational studies of hospitalized and critically-ill patients reported that treatment with oseltamivir reduced disease severity, complications and mortality [55] [56] [57] . In a Chinese study of 1291 patients with confirmed H1N1 influenza A infection, oseltamivir reduced the risk of developing pneumonia, even when administered after the first 48 h of symptom onset (OR 0.12, 95 % CI [0.08-0.18]) [58] . In another retrospective study of 304 hematopoietic stem cell transplant recipients with influenza infection, 161 patients had H1N1 influenza A confirmed infection, and both early and delayed administration of antiviral therapy was shown to be beneficial in terms of decreased risk of lower respiratory tract compromise (OR00.04, 95 % CI [0-0.2] vs. OR00.14, 95 % CI [0-0.7]) [59] . An intravenous form of zanamivir is under development, and was made available during the 2009 H1N1 influenza A pandemic for severely ill patients with highly suspected or confirmed oseltamivir-resistant infection that could not tolerate inhaled zanamivir. Several studies reported favorable outcomes with the use of IV zanamivir [60] [61] [62] [63] .