Klebsiella Pneumonia

Pneumonia caused by Klebsiella pneumoniae, an encapsulated Gram negative bacillus. In the community it affects alcohol misusers, diabetics, patients with COPD, malnourished and elderly patients, and in hospital it is a leading cause of hospital acquired and ventilator associated pneumonia. Hypervirulent strains (more frequent in Asia and parts of Africa) cause community infection with liver abscess, endophthalmitis and meningitis in healthy people.

• Klebsiella accounts for about 3 to 5% of community acquired pneumonia in Western settings and more in the tropics, and for about 10 to 20% of hospital acquired pneumonia.
• Mortality is about 20 to 50%, higher with bacteraemia, shock and resistant strains. Extended spectrum beta lactamase producers and carbapenem resistant strains (KPC, NDM and OXA-48 enzymes) are widespread in hospitals, including in East Africa, where a large proportion of hospital isolates produce extended spectrum beta lactamases.
• Mechanism: the polysaccharide capsule resists phagocytosis; necrosis and abscess formation in the upper lobes are characteristic, with a heavy, thick exudate that expands the lobe and bulges the fissure.

• Abrupt onset with high fever, rigors, pleuritic pain, dyspnoea, and cough with thick, gelatinous, blood tinged ("redcurrant jelly") sputum. Patients look toxic and may be hypotensive.
• Hypervirulent strains: fever with liver abscess (right upper quadrant pain), eye pain or visual loss, meningism.
• Differential diagnosis: pneumococcal and staphylococcal pneumonia, tuberculosis (upper lobe cavitation), melioidosis, anaerobic lung abscess, lung cancer with obstruction, fungal infection.
• Complications: necrotising pneumonia, lung abscess, empyema (about 10 to 25%), bronchopleural fistula, bacteraemia, septic shock, ARDS, and metastatic infection (liver abscess, meningitis, endophthalmitis, osteomyelitis, septic arthritis).

• Chest X-ray and CT: upper lobe consolidation with a bulging fissure sign, rapid cavitation, abscess, effusion.
• Blood cultures; sputum Gram stain (encapsulated Gram negative bacilli) and culture with extended spectrum beta lactamase and carbapenemase testing; pleural fluid culture. A positive string test suggests a hypervirulent strain.
• Blood tests: full blood count, CRP, procalcitonin, glucose and HbA1c, liver function, creatinine, lactate, HIV test.
• Abdominal ultrasound or CT for liver abscess in hypervirulent infection; eye review and lumbar puncture (when safe) for metastatic spread.

• Susceptible strains:
  • Ceftriaxone 2 g IV daily, or cefotaxime 2 g IV every 8 hours, with gentamicin 5 to 7 mg/kg IV daily (trough less than 1 mg/L) for the first 48 to 72 hours in severe disease.
  • Ciprofloxacin 400 mg IV every 8 to 12 hours (500 to 750 mg orally twice daily) or levofloxacin 750 mg daily as alternatives or for oral step down.
  • Piperacillin tazobactam 4.5 g IV every 6 to 8 hours when susceptible.
• Extended spectrum beta lactamase producers: meropenem 1 g IV every 8 hours (2 g every 8 hours in meningitis), or ertapenem 1 g IV daily for non-severe infection.
• Carbapenem resistant strains (choose by the carbapenemase type and local susceptibility):
  • KPC or OXA-48: ceftazidime avibactam 2.5 g IV every 8 hours (3-hour infusion), or meropenem vaborbactam 4 g IV every 8 hours.
  • NDM: ceftazidime avibactam 2.5 g IV every 8 hours plus aztreonam 2 g IV every 8 hours, or cefiderocol 2 g IV every 8 hours.
  • When these are unavailable: colistin loading dose 9 million units IV then 4.5 million units every 12 hours (adjust to creatinine clearance; monitor for kidney injury) plus meropenem 2 g IV every 8 hours as an extended infusion, with or without tigecycline 100 mg then 50 mg every 12 hours (not for bacteraemia). Inhaled colistin 1 to 2 million units every 8 to 12 hours may be added in ventilator associated pneumonia (evidence is limited).
• Duration: 7 to 10 days when stable; 14 days for bacteraemia with a metastatic focus; 3 to 6 weeks for abscess; liver abscess 4 to 6 weeks with drainage.
• Procedures: chest drain for empyema (intrapleural alteplase 10 mg plus dornase alfa 5 mg twice daily for 3 days when loculated); percutaneous or surgical drainage of abscess not responding by 2 to 3 weeks; lobectomy for necrotising pneumonia failing medical therapy or for massive haemoptysis.
• Supportive care: oxygen, ventilation with 6 mL/kg predicted body weight, IV fluids, vasopressors (noradrenaline 0.05 to 0.5 micrograms/kg/min), glycaemic control with insulin, alcohol withdrawal prevention with thiamine 100 mg IV daily and chlordiazepoxide as needed, nutrition, enoxaparin 40 mg SC daily.
• Prevention: hand hygiene, antibiotic stewardship, contact precautions for resistant strains, glycaemic control, alcohol reduction, early removal of lines and tubes.
• Special groups:
  • Children and neonates: ceftriaxone 50 to 100 mg/kg/day (not in neonates with jaundice), meropenem 20 mg/kg every 8 hours, gentamicin 5 to 7.5 mg/kg daily.
  • Pregnancy: ceftriaxone or meropenem; avoid fluoroquinolones; use aminoglycosides only when essential.
  • Renal impairment: adjust beta lactams, aminoglycosides and colistin; avoid combining nephrotoxic agents where possible.
  • HIV and diabetes: treat the underlying disease aggressively.
• Red flags: shock, haemoptysis, rapidly progressive cavitation, positive blood cultures, severe headache or eye pain (metastatic infection), rising creatinine on colistin or aminoglycosides.
• Follow up: review at 48 to 72 hours with cultures; chest X-ray at 6 weeks (CT if a cavity or opacity persists); liver imaging after hypervirulent infection; repeat blood cultures after treatment for relapse.