Pseudomonas Pneumonia

Pneumonia caused by Pseudomonas aeruginosa, a non-fermenting Gram negative bacillus with intrinsic and acquired antibiotic resistance. It is mostly hospital acquired (10 to 20% of ventilator associated pneumonia) and occurs in patients with bronchiectasis, cystic fibrosis, severe COPD, neutropenia, structural lung disease, tracheostomy, burns, recent broad spectrum antibiotics, prolonged steroids, and advanced HIV. Community acquired Pseudomonas pneumonia is uncommon (less than 5%).

• Mortality is about 30 to 60% in ventilator associated pneumonia and bacteraemic disease. Multidrug resistant and extensively drug resistant strains are increasing.
• Mechanism: biofilm formation, virulence factors (exotoxin A, elastase, type III secretion), and efflux pumps and beta lactamases that confer resistance. Chronic airway infection in bronchiectasis and cystic fibrosis causes repeated exacerbations and accelerated lung decline.

• Fever, increased purulent (often green) sputum, dyspnoea, pleuritic pain, rigors, and rapid progression to respiratory failure and shock. Necrotising pneumonia with cavitation and haemoptysis can occur. Ecthyma gangrenosum (skin necrosis) signals bacteraemia, especially in neutropenia.
• Chronic infection: persistent productive cough, increasing sputum volume, haemoptysis, weight loss, and recurrent exacerbations.
• Differential diagnosis: Klebsiella and staphylococcal pneumonia, non-tuberculous mycobacterial infection, aspergillosis, tuberculosis, bronchiectasis exacerbation from other pathogens, ARDS, pulmonary embolism, vasculitis.
• Complications: respiratory failure, ARDS, septic shock, empyema, lung abscess, bronchopleural fistula, massive haemoptysis, chronic colonisation with decline in lung function.

• Chest X-ray and CT: consolidation, nodules, cavities, bronchiectasis, effusion.
• Sputum or endotracheal aspirate culture with full susceptibility testing, including carbapenemase testing; bronchoalveolar lavage in ventilated or immunosuppressed patients; blood cultures; pleural fluid culture.
• Blood tests: full blood count (neutropenia), CRP, procalcitonin, creatinine, liver function, lactate, glucose, HIV test, immunoglobulins in recurrent disease.
• In bronchiectasis and cystic fibrosis: sputum cultures at every exacerbation and every 3 months, spirometry, and a search for non-tuberculous mycobacteria and Aspergillus.

• Use an anti-pseudomonal beta lactam from the start, with a second agent from a different class in septic shock, neutropenia and when multidrug resistance is likely; narrow after susceptibilities return.
• Anti-pseudomonal beta lactam (choose one):
  • Piperacillin tazobactam 4.5 g IV every 6 hours (or 4.5 g every 8 hours as a 4-hour infusion).
  • Cefepime 2 g IV every 8 hours, or ceftazidime 2 g IV every 8 hours.
  • Meropenem 1 g IV every 8 hours (2 g every 8 hours in severe disease), or imipenem cilastatin 500 mg IV every 6 hours.
• Second agent when indicated:
  • Ciprofloxacin 400 mg IV every 8 hours (500 to 750 mg orally twice daily) or levofloxacin 750 mg daily.
  • Tobramycin or gentamicin 5 to 7 mg/kg IV daily (trough less than 1 mg/L), or amikacin 15 to 20 mg/kg IV daily.
• Difficult-to-treat resistance:
  • Ceftolozane tazobactam 3 g IV every 8 hours (hospital acquired and ventilator associated pneumonia dose).
  • Ceftazidime avibactam 2.5 g IV every 8 hours (3-hour infusion).
  • Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours.
  • Cefiderocol 2 g IV every 8 hours (3-hour infusion).
  • Colistin loading dose 9 million units IV then 4.5 million units every 12 hours (adjust for renal function; monitor creatinine), with or without inhaled colistin 1 to 2 million units every 8 to 12 hours (evidence is limited).
• Duration: 7 days for hospital acquired and ventilator associated pneumonia; 10 to 14 days for bacteraemia, necrotising pneumonia and cystic fibrosis exacerbations; abscess and empyema longer with drainage.
• Chronic infection in bronchiectasis and cystic fibrosis:
  • First isolation (eradication): ciprofloxacin 750 mg orally twice daily for 2 to 3 weeks, followed by inhaled tobramycin 300 mg nebulised twice daily for 28 days (or inhaled colistin 1 to 2 million units twice daily).
  • Chronic suppression after 3 or more exacerbations a year: inhaled tobramycin 300 mg twice daily on alternate 28-day cycles, or inhaled colistin 1 to 2 million units twice daily; azithromycin 250 mg daily or 500 mg three times a week (exclude non-tuberculous mycobacteria and check the QT interval first).
  • Airway clearance: physiotherapy twice daily, hypertonic saline 7% nebulised twice daily, and for cystic fibrosis dornase alfa 2.5 mg nebulised daily.
  • Acute exacerbation: 14 days of an anti-pseudomonal regimen (IV for severe, oral ciprofloxacin 750 mg twice daily for mild).
• Supportive care: oxygen, lung protective ventilation (6 mL/kg predicted body weight), vasopressors, nutrition, enoxaparin 40 mg SC daily, early mobilisation; venovenous ECMO for refractory hypoxaemia.
• Neutropenic patients: cefepime 2 g IV every 8 hours or meropenem 1 g IV every 8 hours started within 1 hour, plus an aminoglycoside or ciprofloxacin in shock; consider antifungal cover when fever persists beyond 4 to 7 days.
• Source control: remove lines, drain empyema and abscess, and manage bronchopleural fistula.
• Prevention: hand hygiene, sterile technique, avoidance of contaminated water in ventilated patients, early extubation, antibiotic stewardship, and cross infection control for cystic fibrosis clinics.
• Special groups:
  • Children: ceftazidime 50 mg/kg every 8 hours (maximum 2 g), meropenem 20 to 40 mg/kg every 8 hours, tobramycin 7 to 10 mg/kg once daily in cystic fibrosis.
  • Pregnancy: anti-pseudomonal beta lactams; avoid fluoroquinolones; use aminoglycosides only when essential, with levels.
  • Renal impairment: adjust beta lactams and aminoglycosides, and avoid colistin with other nephrotoxic drugs.
  • Cystic fibrosis: higher and more frequent beta lactam dosing and specialist centre care.
• Red flags: shock, new cavities, haemoptysis, ecthyma gangrenosum, neutropenia, rapid oxygen deterioration, resistance on culture.
• Follow up: daily review in hospital; repeat sputum cultures after treatment; yearly CT and spirometry in bronchiectasis; specialist respiratory review every 3 to 6 months for chronic colonisation.