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Infectious Diseases›Condition·Updated Jun 27, 2026·v1

Influenza

Influenza is a common viral respiratory infection causing seasonal epidemics with substantial global morbidity and mortality. Early diagnosis by RT-PCR and prompt initiation of oseltamivir (within 48 hours) reduce symptom duration, complications, and hospitalizations. Annual vaccination remains the most effective preventive strategy, particularly for high-risk groups. Management includes supportive care, avoidance of routine corticosteroids, and vigilance for bacterial superinfection. Antiviral resistance (especially to adamantanes and emerging baloxavir resistance) requires ongoing surveillance and stewardship.

High Evidence628 references·2,118 words·9 min read·v1
influenzafluantiviraloseltamivirbaloxavirvaccinationpneumoniaARDSinfection controlpublic healthseasonal influenzapandemic

Quick Reference

RxDrug of choiceOseltamivir 75 mg PO BID ×5 days (adults); start as soon as possible, ideally within 48 hours of symptom onset.
AltAlternativesBaloxavir marboxil (single dose 40 mg [<80 kg] or 80 mg [≥80 kg]) for uncomplicated outpatients ≥5 years; peramivir 600 mg IV once daily if oral not feasible; zanamivir 10 mg inhaled BID for oseltamivir-resistant strains.
⊘AvoidAmantadine and rimantadine (universal resistance); zanamivir in asthma/COPD; baloxavir in severe influenza or hospitalized patients; avoid routine corticosteroids.
DxTest of choiceRT-PCR on nasopharyngeal swab (sensitivity 90.9%, specificity 96.1%).
ScKey scorePneumonia Severity Index (PSI) score ≥91 (class IV-V) or SOFA score ≥6 at 24 hours predicts need for ICU admission.
→When to referImmunocompromised with persistent shedding or suspected resistance, avian influenza, severe ARDS requiring ECMO, or diagnostic uncertainty.
Treat empirically with oseltamivir without waiting for test results in hospitalized/high-risk patients; annual vaccination is the best prevention, with high-dose vaccine preferred for those ≥65 years.
Influenza (flu) is an acute viral respiratory infection caused by *Orthomyxoviridae*, causing annual epidemics and occasional pandemics with 3-5 million severe cases and 290,000-650,000 deaths globally each year [1]. Rapid diagnosis, early antiviral therapy, and vaccination are cornerstones of management.

Overview and Recommendations

Background

  • •Influenza is an acute viral respiratory infection caused by influenza A and B viruses (Orthomyxoviridae family) that produces annual epidemics and occasional pandemics, resulting in an estimated 1 billion infections, 3-5 million severe cases, and 290,000-650,000 respiratory deaths globally each year.
  • •Influenza A viruses are classified by hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins; seasonal illness is caused by A(H1N1)pdm09 and A(H3N2) subtypes, while avian subtypes (H5N1, H7N9) carry high mortality and pandemic potential.
  • •Influenza B viruses divide into Victoria and Yamagata lineages; since the COVID-19 pandemic, B/Yamagata has not been detected, prompting consideration of removing it from quadrivalent vaccines.
  • •The virus is transmitted primarily via large respiratory droplets and aerosols, with an incubation period of 1-4 days (mean 2 days); adults shed virus from 1 day before symptom onset through 5-7 days, while children and immunocompromised individuals may shed for ≥10 days.
  • •High-risk groups for severe disease include age <2 or ≥65 years, pregnancy (especially third trimester), chronic medical conditions (cardiovascular, pulmonary, renal, hepatic, neurologic), immunosuppression, obesity (BMI ≥40), and residence in long-term care facilities.

Evaluation

  • •Suspect influenza in any patient with acute onset of fever, cough, and myalgia during respiratory virus season (October-April in Northern Hemisphere).
  • •Ask about symptom onset (abrupt vs gradual), fever height, dyspnea, chest pain, altered mental status, and gastrointestinal symptoms (more common in children).
  • •Ask about high-risk conditions: age, pregnancy, chronic medical conditions (COPD, asthma, heart failure, diabetes, renal disease, neurologic disease), immunosuppression (transplant, HIV, chemotherapy), obesity, and long-term care residence.
  • •Ask about vaccination status for the current season and any known influenza exposures.
  • •Examine vital signs: fever (≥38°C), tachycardia, tachypnea, hypoxia (SpO₂ <90%).
  • •Perform lung auscultation: clear early; crackles or wheezes suggest pneumonia or secondary bacterial infection.
  • •Examine for altered mental status, seizures, or focal deficits, may indicate influenza-associated acute necrotizing encephalopathy (ANE), especially in children.
  • •Order a nasopharyngeal swab for RT-PCR (gold standard), sensitivity 90.9%, specificity 96.1%; do not wait for results to start antivirals in hospitalized or high-risk patients.
  • •Rapid antigen detection tests (RIDTs) have sensitivity only ~61%; a negative RIDT does not rule out influenza and should prompt RT-PCR if clinical suspicion is high.
  • •Order chest imaging (X-ray or CT) if hypoxia, dyspnea, or suspected pneumonia; patchy bilateral infiltrates suggest primary viral pneumonia, while consolidation suggests secondary bacterial infection.
  • •Order blood cultures, sputum culture, and procalcitonin if bacterial coinfection is suspected (consolidation, leukocytosis, procalcitonin >0.5 ng/mL).
  • •Assess severity using the Pneumonia Severity Index (PSI) or CURB-65; PSI class IV-V (score ≥91) predicts 9-fold higher mortality and warrants hospital admission.
  • •For hospitalized patients, calculate SOFA score at 24 hours: score ≥6 predicts ICU need with 82% sensitivity and 76% specificity.
  • •Differential diagnosis includes RSV, rhinovirus, seasonal coronaviruses, SARS-CoV-2, human metapneumovirus, parainfluenza, adenovirus, and bacterial/atypical pneumonia (S. pneumoniae, Mycoplasma, Chlamydia, Legionella).

Management

  • •Initiate empiric antiviral therapy immediately in all hospitalized patients and high-risk outpatients without waiting for laboratory confirmation, time to first dose is the most modifiable predictor of outcome.
  • •Start oseltamivir 75 mg orally twice daily for 5 days in adults and children ≥13 years; weight-based dosing for children <13 years: 30 mg BID (≤15 kg), 45 mg BID (>15-23 kg), 60 mg BID (>23-40 kg), 75 mg BID (>40 kg).
  • •For hospitalized patients with severe illness, consider extending oseltamivir to 10 days; high-dose oseltamivir (150 mg BID) has not shown superiority over standard dose.
  • •Adjust oseltamivir for renal impairment: CrCl 30-60 mL/min → 30 mg BID; CrCl <30 mL/min → 30 mg once daily.
  • •Alternative for uncomplicated outpatients ≥5 years: baloxavir marboxil single oral dose 40 mg (weight <80 kg) or 80 mg (≥80 kg), noninferior to oseltamivir for symptom relief and reduces household transmission (NNT=8).
  • •Do NOT use baloxavir for severe influenza or hospitalized patients; the FLAGSTONE trial showed no benefit.
  • •If oral therapy is not feasible (e.g., intubation, impaired absorption), use IV peramivir 600 mg once daily (adjust for CrCl <50 mL/min to 300 mg daily; CrCl <30 mL/min to 150 mg daily).
  • •For oseltamivir-resistant influenza (e.g., H1N1 with H275Y mutation), use zanamivir 10 mg inhaled BID ×5 days (contraindicated in asthma/COPD) or peramivir IV.
  • •Do NOT use amantadine or rimantadine, >99% of circulating strains are resistant.
  • •Provide supportive care: supplemental oxygen to maintain SpO₂ ≥92%, IV fluids for dehydration, antipyretics (acetaminophen or NSAIDs).
  • •Do NOT routinely use systemic corticosteroids for influenza pneumonia, no mortality benefit and increased risk of secondary infections.
  • •Consider empiric antibiotics for suspected bacterial coinfection (consolidation, leukocytosis, procalcitonin >0.5 ng/mL) covering S. pneumoniae, S. aureus (including MRSA), and H. influenzae.
  • •Monitor clinical response daily (fever, respiratory status, oxygen saturation); if no improvement after 48-72 hours, consider repeat influenza testing for resistance or coinfection.
  • •Discharge criteria: afebrile for ≥24 hours without antipyretics, SpO₂ ≥92% on room air, tolerating oral intake, and no ongoing respiratory distress.
  • •Refer to infectious disease specialist for immunocompromised patients with persistent viral shedding, suspected resistance, or avian influenza.

Board Review — High Yield

  • •Rapid antigen test, Sensitivity only ~61%; negative result does NOT rule out influenza; always confirm with RT-PCR in high-risk patients.
  • •Oseltamivir, First-line antiviral; reduces symptom duration by ~1 day and lowers risk of lower respiratory tract complications and hospitalization.
  • •Baloxavir, Single-dose alternative for uncomplicated outpatients; reduces household transmission; NOT for severe disease.
  • •H275Y mutation, Confers high-level oseltamivir resistance; treat with zanamivir or peramivir.
  • •Influenza-associated acute necrotizing encephalopathy (ANE), Rare but devastating complication in children; rapid onset of seizures and symmetric thalamic lesions on MRI; mortality ~31%.
  • •HD-IIV (high-dose influenza vaccine), Recommended for adults ≥65 years; reduces hospitalization for influenza/pneumonia by 23% vs standard-dose.
  • •Secondary bacterial pneumonia, Typically occurs 4-14 days after symptom onset; most common pathogens: S. pneumoniae, S. aureus (including MRSA), S. pyogenes.
  • •Influenza-associated pulmonary aspergillosis (IAPA), Occurs in 10-20% of ICU patients with severe influenza; treat with voriconazole or isavuconazole.
  • •Pregnancy, High risk for severe disease; oseltamivir is safe and recommended; influenza vaccine protects both mother and neonate.
  • •Antiviral stewardship, Do not use adamantanes; limit baloxavir to outpatients; monitor for resistance in immunocompromised hosts.

Deep Dive — Evidence Details

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