The purposes of this study are to evaluate the pharmacokinetics (affect the body has on a drug), and pharmacodynamics (affect the drug has on the body) and safety of an experimental intravenous (within a vein) flu medication, peramivir, in children. Participants will include 63 hospitalized children with confirmed flu. Children will be grouped according to age and younger children will not receive drug until safety data from the groups of older children are reviewed. Hospitalized children may receive up to 5 doses of peramivir. Study procedures include: nasal/throat swabs, reporting any experienced side effects, physical examination including assessment of the nervous system, and blood sample collection. Participants will be involved in study related procedures for up to 28 days.

Infants and young children are at greatest risk of mortality from epidemic influenza. Influenza medications currently approved for use in the United States are administered orally or via inhalation. Availability of a parenteral influenza medication could be of great importance in medical and public health responses to both seasonal and pandemic influenza. Peramivir is an experimental parenteral influenza drug that is in advanced stages of clinical development. The primary objective of this study is to define the pharmacokinetics (PK) of peramivir in children with confirmed influenza. The secondary objectives are to: assess the safety and tolerability of intravenous (IV) peramivir in children with influenza; assess viral dynamics as a function of drug PK; and assess virus susceptibility to peramivir. This study is a prospective, open-label, age-stratified PK/pharmacodynamic (PD) and safety evaluation of investigational IV peramivir in hospitalized children with influenza infection who are unable to receive or have failed at least three days oseltamivir or zanamivir therapy. A minimum of 63 children with confirmed influenza will be enrolled into 1 of 7 age cohorts: Cohort I (>= 12 years to < 18 years); Cohort II (>= 6 years to < 12 years); Cohort III (>= 2 years to < 6 years); Cohort IV (>= 181 days to < 2 years); Cohort V (>= 91 days to < 181 days); Cohort VI (>= 31 days to < 91 days) and Cohort VII (Birth to < 31 days). Only hospitalized children will be enrolled. At study onset, Cohorts I, II and III (children from >=2 years to < 18 years of age) will be enrolled initially. When PK and safety data from 9 total subjects enrolled Cohort I, Cohort II and/or Cohort IIII are available and reviewed by the study's Data and Safety Monitoring Board (DSMB), Cohorts IV-VII will be opened for enrollment. The initial doses selected for use were based on modeling and from a recently completed clinical trial study of a fixed dose (10 mg/kg) of peramivir in pediatric patients with influenza. In the current study, PK data will be obtained in a real time basis, and doses in each cohort may be modified if the target exposure [area under the curve (AUC) 24] falls outside of a pre-specified range. Additional enrollments may be allowed if the dose requires modification in a given cohort. In the event of a public health emergency, the National Institutes of Health (NIH), DSMB, or Food and Drug Administration (FDA) may that all cohorts be open for enrollment. Subjects will receive IV Peramivir once daily for 5 days or until the day of hospital discharge, whichever comes first, and PK blood draws will be obtained around the second dose. In addition to PK and PD, this study will carefully assess clinical disease course and adverse events (AEs), including neurologic AEs. Safety evaluations also will include neurologic assessments, general physical assessments, and AE and serious adverse event (SAE) reporting. Sequential nasopharyngeal specimens will be obtained for virologic assessments, including viral cultures, polymerase chain reaction (PCR) for viral ribonucleic acid (RNA) (quantitative), and analysis of antiviral resistance.

Inclusion Criteria: -Signed informed consent from parent(s) or legal guardian(s), and signed informed assent as age appropriate. -Age: Cohort I:>/= 12 years to < 18 years. Cohort II: >/= 6 years to < 12 years. Cohort III: >/= 2 years to < 6 years. Cohort IV: >/= 181 days to < 2 years. Cohort V: >/= 91 days to < 181 days. Cohort VI: >/= 31 days to < 91 days. Cohort VII: Birth to < 31 days -Confirmed laboratory diagnosis of influenza by viral culture, polymerase chain reaction (PCR), or rapid influenza diagnostic test. -Hospitalized with influenza or complications of influenza -Subject cannot tolerate oral or inhaled influenza antiviral therapy, or has not responded to at least 3 days of oral or inhaled influenza antiviral therapy, as determined by the physician. -Females of childbearing potential must have one of the following: a. Subject has been sexually abstinent for the 4 weeks prior to date of screening evaluation and is willing to remain abstinent through 4 weeks after study drug administration b. Subject has been using oral contraceptives or other form of hormonal birth control for 3 months prior to the study and will continue to use through 4 weeks after study-drug discontinuation c. Subject has been using an intra-uterine device, or adequate double-barrier method (such as condom or diaphragm with spermicide) as birth control for 4 weeks prior to date of screening and will continue use through 4 weeks after study drug administration d. Subject is surgically sterile (e.g., hysterectomy, tubal ligation) -Sexually active males must ensure that their female partners of childbearing potential will utilize approved contraceptive methods to avoid pregnancy Exclusion Criteria: -Currently receiving peritoneal dialysis. -Currently requiring extracorporeal membrane oxygenation (ECMO). -Imminent demise. -Documented H275Y mutation (note: it is unlikely that resistance testing will have been completed for most subjects). -New onset seizure disorder with this acute illness. -Suspicion of significant renal impairment (e.g., polycystic renal disease, nephrectomy, renal transplantation within the past 6 months, renal agenesis, chronic renal failure, anuria). -Pregnancy (positive urine or serum pregnancy test at screening evaluation for females of childbearing potential). -Females who are breastfeeding. -Inability to comply with protocol-required procedures. -Presence of any pre-existing condition that, in the opinion of the investigator, would place the subject at an unreasonable increased risk through participation in this study. -Alternate explanation for clinical findings, as determined by the investigator.