Morphology: Enveloped, single-stranded negative-sense RNA virus. Family Orthomyxoviridae. Subtyped by HA + NA proteins (H1N1, H3N2 currently circulating in humans). **Antigenic drift** (point mutations, seasonal) + **antigenic shift** (reassortment, pandemic potential — H5N1, H7N9 avian).
Typical drugs
- #1Oseltamivir— **75 mg PO BID × 5 days** — start within 48 h for max benefit; treat hospitalized / severe / immunocompromised regardless of timing.
- #2Baloxavir Marboxil— **Single-dose** 40 mg (<80 kg) or 80 mg (≥80 kg) PO. Equivalent to oseltamivir in uncomplicated disease.
Empiric therapy when resistant
Treatment-failure influenza A → baloxavir (if not used initially) or zanamivir inhaled. Avian H5N1 / H7N9 — oseltamivir 150 mg BID × 10 days + ID consult (some isolates resistant; mortality high).
Resistance mechanisms
altered-target
**NA H275Y mutation** → oseltamivir resistance (H1N1)
Example: Rare in currently circulating strains but watch in treatment failures or PEP failures. Baloxavir or zanamivir alternatives.
altered-target
**PA I38 mutations** → baloxavir resistance
Example: Can emerge during baloxavir treatment (more common in pediatric). Clinical significance modest currently.
Resistance notes
Adamantanes (amantadine, rimantadine) — almost universal resistance now in influenza A. Don't use.
Pearls
Treat hospitalized + severe disease regardless of symptom onset timing. Outpatient mild disease: start within 48 h for symptom reduction (~1 day shorter); after 48 h benefits marginal in immunocompetent. High-risk groups (pregnant, immunocompromised, ≥65, chronic lung/heart disease, BMI ≥40, residents of long-term care) — treat with oseltamivir even outside 48-h window. Bacterial superinfection (S. aureus, S. pneumoniae, GAS) — flu + worsening or biphasic illness → suspect; CAP + MRSA empirics. Annual vaccine is the prevention pillar; trivalent vs quadrivalent vs cell-cultured vs recombinant vs high-dose / adjuvanted for ≥65.