Post Influenza Pneumonia

Pneumonia that follows or complicates influenza, either as secondary bacterial pneumonia (a second fever after initial improvement, usually 4 to 14 days after onset), primary influenza viral pneumonia (progressive hypoxaemia from the start), or mixed disease. Bacterial co-infection occurs in about 10 to 30% of hospitalised patients with influenza and in up to about half of fatal cases.

• Organisms: Streptococcus pneumoniae (commonest), Staphylococcus aureus (including methicillin resistant and Panton-Valentine leucocidin strains, with necrotising pneumonia and high mortality), group A streptococcus, and Haemophilus influenzae. Invasive aspergillosis can complicate severe influenza in intensive care (influenza associated pulmonary aspergillosis in about 10 to 20% of ventilated patients).
• Mechanism: viral injury to the airway epithelium, loss of ciliary clearance, exposure of bacterial receptors by viral neuraminidase, and impaired macrophage and neutrophil function.
• Risk factors: age 65 or over, infants, pregnancy, chronic heart or lung disease, diabetes, obesity, immunosuppression, chronic kidney disease, residence in care homes, and absent vaccination.
• Mortality is about 10 to 30% in admitted patients, and higher with Staphylococcus aureus and with delayed antiviral therapy.

• A typical influenza illness (fever, myalgia, headache, cough) with initial improvement, then new high fever, rigors, purulent or blood stained sputum, pleuritic chest pain, worsening dyspnoea and sometimes shock. Primary viral pneumonia presents with continuing fever, severe dyspnoea, dry cough, bilateral crackles and early hypoxaemia.
• Necrotising Staphylococcus aureus disease: haemoptysis, leucopenia, rapid cavitation, and shock.
• Differential diagnosis: primary influenza pneumonia and ARDS, heart failure, pulmonary embolism, myocarditis, invasive aspergillosis, Pneumocystis pneumonia, tuberculosis, aspiration pneumonia, other viral pneumonias (SARS-CoV-2, respiratory syncytial virus).
• Complications: necrotising pneumonia, empyema, ARDS, septic shock, toxic shock syndrome, myocarditis, encephalopathy, rhabdomyolysis, acute kidney injury, invasive aspergillosis, and exacerbation of heart failure or COPD.

• Nasopharyngeal or lower respiratory tract PCR for influenza A and B (rapid antigen tests are insensitive); respiratory viral panel including SARS-CoV-2.
• Chest X-ray or CT: lobar or multilobar consolidation (bacterial), diffuse ground glass opacities (viral), cavities or effusion (Staphylococcus aureus).
• Blood cultures; sputum or tracheal aspirate Gram stain and culture; pneumococcal and Legionella urinary antigens; nasal PCR for methicillin resistant Staphylococcus aureus; procalcitonin (a high value supports bacterial co-infection); full blood count (lymphopenia in influenza, leucocytosis or leucopenia in bacterial disease); CRP, creatinine, liver function, creatine kinase, lactate, troponin.
• In ventilated patients: bronchoalveolar lavage for culture and galactomannan, and serum galactomannan, to look for aspergillosis.

• Antiviral therapy (start immediately, without waiting for confirmation, and even beyond 48 hours in admitted or severe patients):
  • Oseltamivir 75 mg orally (or by nasogastric tube) twice daily for 5 days; extend to 10 days in severe or immunosuppressed patients. Reduce when creatinine clearance is 30 to 60 mL/min (30 mg twice daily) and 10 to 30 mL/min (30 mg once daily).
  • Alternatives: IV peramivir 600 mg once daily for 1 to 5 days (adjust for renal function); inhaled zanamivir 10 mg twice daily in mild disease (avoid in severe disease and in asthma or COPD); baloxavir 40 mg once (80 mg if 80 kg or more) in uncomplicated disease (limited evidence in severe disease).
• Antibacterial therapy (cover Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae):
  • Co-amoxiclav 1.2 g IV every 8 hours, or ceftriaxone 2 g IV daily, in non-severe disease.
  • Severe disease, necrotising pneumonia or methicillin resistant Staphylococcus aureus risk: ceftriaxone 2 g IV daily plus flucloxacillin 2 g IV every 6 hours (or cefazolin 2 g every 8 hours) and linezolid 600 mg IV every 12 hours, or vancomycin loading dose 25 to 30 mg/kg then 15 to 20 mg/kg every 8 to 12 hours (trough 15 to 20 mg/L).
  • Toxin suppression in necrotising disease: add clindamycin 600 mg IV every 8 hours (or rely on linezolid).
  • Add a macrolide (clarithromycin 500 mg twice daily or azithromycin 500 mg daily) when Legionella or atypical organisms are possible.
  • Penicillin allergy: levofloxacin 750 mg daily (with vancomycin for staphylococcal cover).
  • Duration: 7 days for non-severe bacterial disease; 14 days or longer for Staphylococcus aureus; stop earlier when procalcitonin falls and the patient is stable.
• Corticosteroids: do not give routinely in influenza (they can prolong viral shedding and raise mortality). Use hydrocortisone 200 mg/day IV only for refractory septic shock.
• Invasive aspergillosis (proven or probable): voriconazole 6 mg/kg IV every 12 hours for 2 doses then 4 mg/kg every 12 hours (monitor trough 1 to 5.5 mg/L, liver function, visual symptoms), or isavuconazole 372 mg every 8 hours for 6 doses then 372 mg daily; duration at least 6 to 12 weeks.
• Supportive care: oxygen, high flow nasal oxygen, lung protective ventilation (6 mL/kg predicted body weight), prone positioning for severe hypoxaemia, vasopressors (noradrenaline 0.05 to 0.5 micrograms/kg/min), venovenous ECMO for refractory respiratory failure, enoxaparin 40 mg SC daily, droplet isolation precautions.
• Empyema: chest drain with intrapleural alteplase 10 mg plus dornase alfa 5 mg twice daily for 3 days, or thoracoscopic debridement.
• Prevention:
  • Yearly influenza vaccine for everyone 6 months or older, and especially pregnant women, the elderly and those with chronic disease; pneumococcal conjugate vaccine for adults 65 or older and high risk patients (20-valent single dose, or 15-valent followed by 23-valent polysaccharide vaccine 8 weeks or more later).
  • Post-exposure prophylaxis for high risk contacts: oseltamivir 75 mg once daily for 7 to 10 days.
• Special groups:
  • Pregnancy: oseltamivir at once; co-amoxiclav or ceftriaxone for bacterial infection; avoid doxycycline and fluoroquinolones; deliver only for obstetric indications.
  • Children: oseltamivir 30 mg twice daily (15 kg or less), 45 mg (over 15 to 23 kg), 60 mg (over 23 to 40 kg), 75 mg (over 40 kg); infants under 1 year 3 mg/kg twice daily; ceftriaxone 50 to 100 mg/kg/day, flucloxacillin 50 mg/kg every 6 hours, vancomycin 15 mg/kg every 6 hours.
  • Immunosuppressed patients: prolonged oseltamivir (10 days or longer), early bronchoscopy for opportunistic infection.
  • Renal impairment: adjust oseltamivir, peramivir, vancomycin and other doses.
• Red flags: second fever after improvement, haemoptysis, leucopenia with shock, rising oxygen requirement, multilobar cavitation, new neurological signs.
• Follow up: review at 48 to 72 hours and 6 weeks; repeat chest X-ray at 6 weeks in smokers over 50 or with persistent symptoms; update influenza and pneumococcal vaccination.