Hospital Acquired Pneumonia

Pneumonia that begins 48 hours or more after admission and was not incubating at admission. Ventilator associated pneumonia begins more than 48 hours after intubation. It occurs in about 5 to 20 per 1000 admissions and in about 10 to 25% of ventilated patients, and it is the commonest fatal hospital acquired infection. Mortality is about 20 to 50%, with an attributable mortality of about 10 to 13%.

• Organisms: Staphylococcus aureus (including methicillin resistant), Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter, Serratia, Acinetobacter baumannii and Stenotrophomonas maltophilia; anaerobes and oral flora from aspiration; Legionella in outbreaks; respiratory viruses. Resistant organisms (extended spectrum beta lactamase producers, carbapenem resistant Gram negatives) are common in many African and Asian hospitals, so the local antibiogram guides therapy.
• Mechanism: micro aspiration of colonised oropharyngeal and gastric secretions past an endotracheal cuff or in patients with impaired swallow, cough or consciousness.
• Risk factors for multidrug resistant organisms: antibiotics in the previous 90 days, septic shock, ARDS, 5 or more days in hospital before onset, renal replacement therapy, colonisation, and high local resistance rates. Risk factors for methicillin resistant Staphylococcus aureus: intravenous antibiotics within 90 days, or local prevalence of more than 10 to 20%.

• New or progressive infiltrate plus at least two of: fever greater than 38 degrees Celsius, purulent secretions, leucocytosis or leucopenia, worsening oxygenation or ventilator requirements. Tachypnoea, crackles, bronchial breathing, confusion.
• Differential diagnosis: atelectasis, aspiration pneumonitis, pulmonary oedema, ARDS, pulmonary embolism, drug induced lung injury, alveolar haemorrhage, pulmonary contusion, tracheobronchitis.
• Complications: respiratory failure, septic shock, empyema, lung abscess, necrotising pneumonia, bacteraemia, prolonged ventilation, tracheostomy, and death.

• Chest X-ray or CT: new or progressive infiltrate (a clear film is not sufficient to exclude ventilator associated pneumonia in ventilated patients).
• Blood cultures (two sets). Lower respiratory sample before changing antibiotics: endotracheal aspirate (semiquantitative culture), or bronchoalveolar lavage (significant growth 10^4 colony forming units/mL or more) or protected specimen brush (10^3 or more) when available. Nasal swab PCR for methicillin resistant Staphylococcus aureus has a high negative predictive value and allows early de-escalation.
• Pleural fluid culture and analysis if an effusion is present. Legionella urinary antigen and PCR when exposure is likely. Respiratory viral PCR.
• Procalcitonin trend, CRP, full blood count, creatinine, lactate and arterial blood gas.

• Start empirical therapy at once (within 1 hour in shock), guided by the unit's antibiogram and risk factors, then narrow at 48 to 72 hours using cultures.
• Low risk of mortality and no methicillin resistant Staphylococcus aureus risk (one anti-pseudomonal agent):
  • Piperacillin tazobactam 4.5 g IV every 6 hours (or 4.5 g every 8 hours as a 4-hour infusion), or
  • Cefepime 2 g IV every 8 hours, or ceftazidime 2 g IV every 8 hours, or
  • Meropenem 1 g IV every 8 hours, or imipenem cilastatin 500 mg IV every 6 hours, or
  • Levofloxacin 750 mg IV daily (when beta lactams are contraindicated).
• High risk (septic shock, ventilated, multidrug resistant risk): two anti-pseudomonal agents from different classes plus methicillin resistant Staphylococcus aureus cover:
  • One of piperacillin tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours or meropenem 1 g IV every 8 hours, plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily, or amikacin 15 to 20 mg/kg IV daily (peak 50 to 60 mg/L, trough less than 4 mg/L), or gentamicin or tobramycin 5 to 7 mg/kg IV daily (trough less than 1 mg/L).
  • Methicillin resistant Staphylococcus aureus: vancomycin loading dose 25 to 30 mg/kg IV, then 15 to 20 mg/kg every 8 to 12 hours (trough 15 to 20 mg/L), or linezolid 600 mg IV or orally every 12 hours (preferred in renal impairment and necrotising disease).
  • Extended spectrum beta lactamase producers: meropenem 1 g IV every 8 hours (ertapenem 1 g daily for non-severe, non-Pseudomonas infection).
  • Carbapenem resistant Enterobacterales: ceftazidime avibactam 2.5 g IV every 8 hours (3-hour infusion), or meropenem vaborbactam 4 g IV every 8 hours, or cefiderocol 2 g IV every 8 hours; for metallo-beta-lactamase producers, ceftazidime avibactam plus aztreonam 2 g IV every 8 hours.
  • Carbapenem resistant Acinetobacter: ampicillin sulbactam up to 9 g sulbactam per day in divided doses with a second active agent, or colistin loading dose 9 million units IV then 4.5 million units every 12 hours (adjust for renal function; monitor creatinine) plus meropenem 2 g every 8 hours as an extended infusion. Inhaled colistin 1 to 2 million units every 8 to 12 hours can be added in ventilator associated pneumonia (evidence is limited).
  • Stenotrophomonas: co-trimoxazole 15 to 20 mg/kg/day of trimethoprim in 3 to 4 divided doses.
• Duration: 7 days for most patients; longer for complicated disease (empyema, abscess, bacteraemia with metastatic focus) and for persistent non-fermenting Gram negative infection. Use procalcitonin to guide earlier discontinuation.
• De-escalate once cultures return: stop methicillin resistant Staphylococcus aureus cover if the nasal PCR and cultures are negative, and use a single active agent.
• Supportive care: lung protective ventilation (tidal volume 6 mL/kg predicted body weight, plateau pressure 30 cmH2O or less), oxygen to SpO2 92 to 96%, prone positioning for severe ARDS, vasopressors for shock, enteral nutrition, daily sedation interruption, early mobilisation, enoxaparin 40 mg SC daily.
• Complications: drain empyema, with intrapleural alteplase 10 mg plus dornase alfa 5 mg twice daily for 3 days; prolonged therapy and drainage for abscess.
• Prevention (reduces incidence by about a third to a half): hand hygiene, semi-recumbent position at 30 to 45 degrees, minimising sedation and ventilator days, subglottic secretion drainage for expected ventilation of more than 48 hours, stopping stress ulcer prophylaxis when not needed, oral hygiene with toothbrushing, early enteral feeding, swallow assessment after stroke or extubation, post-operative deep breathing, and antibiotic stewardship.
• Special groups:
  • Children and neonates: weight based dosing (cefepime 50 mg/kg every 8 to 12 hours, meropenem 20 mg/kg every 8 hours, vancomycin 15 mg/kg every 6 hours).
  • Pregnancy: beta lactams; avoid fluoroquinolones, tetracyclines and, where possible, aminoglycosides.
  • Renal impairment: adjust beta lactams, vancomycin and aminoglycosides; avoid colistin and aminoglycosides together where possible.
  • Immunosuppression and neutropenia: cefepime 2 g every 8 hours or meropenem 1 g every 8 hours, and bronchoscopy early for opportunistic infection.
• Red flags: shock, rising oxygen requirement, new multilobar infiltrates, positive blood cultures, failure to improve by 72 hours, new empyema.
• Follow up: daily review of oxygenation, temperature, secretions and cultures; chest X-ray after treatment or at 6 weeks; infection control review for outbreaks.