Sources of infection

The source of infection is the gastrointestinal tract and environment.

• neutropenia
• burns
• environmentally contaminated wounds
• cystic fibrosis.

Neutropenia is the major risk factor in this patient.

Invasive and Toxinogenic

• Bacterial attachment and colonization
  • fimbrial adherence to injured epithelial cells (opportunistic adherence) / pseudomonas pili
  • Biofilm (alginate slime)
• Local invasion (Elastase, Alkaline protease, hemolysins, cytotoxin)
• Disseminated systemic disease (exotoxins A, lipopolysaccharide)

• Intact skin and mucous membrane. (Never infects uncompromised tissues)
• Require both humoral and cell mediated immunity
  • Phagocytes
  • Lymphocytes
  • Complement
• Pseudomonas forms a biofilm which protects the bacteria from host defenses. (phagocytes, Lymphocytes, Complement)
• Extracellular enzymes and Toxins (Proteolytic enzymes, Lecithinase, Collagenase, Elastase, Hemolysins, Leucocidin, LPS, exotoxin A)  contributing to bacterial invasion

Pathology

Necrotizing infection

Pathogenesis of septic shock

The patient is septic. Criteria for sepsis are: 

• Clinical evidence of infection plus 
• Evidence of a systemic response to infection which is manifested by 2 or more of the following conditions: 
  • Temp>38ºC or <36ºC 
  • HR>90/min
  • Respiration >20 breaths/min or PaCO2 <32mm Hg 
  • WBC >12,000 cells/mm3, <4000 cells/mm3 or >10% immature (band) forms

The lipopolysaccharide (LPS) in gram negative organism triggers complement, clotting, fibrinolytic and kinin pathways. 

Fever and inflammation are mediated by cytokines that are released in response to LPS. 

Cytokines which are released include TNF-" , interleukin-1 (IL-1) interferon-m ).

Interleukin-1 is the endogenous pyrogen. TNF-" is the most potent mediator of the pathophysiology of the gram negative sepsis syndrome.

Diagnosis

Gram stain and culture of appropriate secretions/blood.

Ecthyma gangrenosum

Is the result of direct invasion and destruction of the blood vessel walls by the organism.

• Resistance to many of the common antibiotics due to changes in porins
• Combination therapy of cell wall active agent and aminoglycoside
• Piperacillin and gentamicin were given to provide bactericidal antibiotic activity against the pseudomonas. 
• The combination results in synergy. MIC of either drug is decreased by the addition of the second drug, hence the organisms are killed at lower concentrations of the drug.
• Other drugs which may be used are imipenem, ceftazidime and aminoglycosides.

Poor outcome in patients with Pseudomonas sepsis

• Sepsis, pneumonia
• Persistent neutropenia.