Infection In The Immunocompromised Patient

Question 1

Immune Dysfunction Catagories - Neutropenia (Granulocytopenia) and Defects in Phagocyte Function

Answer 1

• Acquired
  
  • Drugs
  • Radiation
  • Cancer
  • Haematopoietic stem cell transplant (HSCT)
• Congenital
• Defects in function
  
  • Leucocyte adhesion defects
  • Chemotactic defects
  • Abnormal phagocytosis
  • Defects in intracellular killing

Question 2

Neutropaenic Sepsis

Answer 2

• Defined as:
  
  • Neutrophil count = 0.5 x 10⁹ plus
    
    • ​Temperature >/= 38°C OR
    • Other signs/symptoms consistent with sepsis
• 1/3 due to bacteraemia

Question 3

Neutropaenic Sepsis - Sources of Bacteraemia

Answer 3

• 85% of infections are due to endogenous flora
• Intravascular catheters
  
  • Most commonly colonised by coagulase negative staphylococci
• Damaged mucosa
  
  • Viridans streptococci
  • Clostridium species
  • Escherichia coli and other coliforms
  • Pseudomonas aeruginosa

Question 4

Neutropaenic Sepsis - Infectious Causes Other Than Bacteraemia

Answer 4

• Upper aerodigestive tract infections
  
  • Candida species
  • Agents of mucormycosis
• Lower respiratory tract infections
  
  • Especially Aspergillus species
• Skin infections
  
  • Candida species
  • Trichosporan species
  • Fusarium species
  • Pseudomonas aeruginosa

Question 5

Neutropaenic Sepsis - Investigation

Answer 5

• History and examination
• Full blood count
• Kidney and liver function tests
  
  • Including albumin
• C-reactive protein
• Lactate
• Blood culture
• Relevant microbiological specimens

Question 6

Neutropaenic Sepsis - Principles of Therapy

Answer 6

• Fever in neutropaenia should be treated as infection unless proven otherwise
• Promp initiation of antibiotic therapy essential
  
  • ‘Door to needle’ time <1 hour
• A bactericidal antibiotic should be used - the immune system lacks capacity to kill
• Antimicrobial regimen should be broad spectrum and directed against principal pathogens encountered
  
  • Subsequently adjust therapy in light of laboratory isolates
• Recovery of neutrophils during therapy may be an important determinant of favourable response

Question 7

Neutropaenic Sepsis - Therapeutic Options

Answer 7

• Monotherapy:
  
  • Anti-pseudomonal beta-lactam
    
    • Piperacillin/tazobactam
    • Imipenem or meropenem
    • Ceftazidime
• Combination therapy:
  
  • Anti-pseudomonal beta-lactam **+ **aminoglycoside:
    
    • Gentamycin
    • Ambikacin
    • Tobramycin

Question 8

Neutropaenic Sepsis - Causes of Persistant Pyrexia

Answer 8

• Pathogen resistant to empiric regiment
• Dosage inadequate
• Breakthrough bacteraemia
• Failure of neutrophil count to rise
• Line-related sepsis
• Cryptic abscess
• Fungal infection
• Viral infection
• Mycobacterial infection
• Underlying disease
• Graft-versus-host disesease

Question 9

Neutropaenic Sepsis - Therapy Protocol

Answer 9

• Confirmed neutropenic sepsis - begin empiric antibiotic therapy
  
  • Review in 48-72 hours - if persistent consider need to broaden antibiotic cover
    
    • Review in further 48-72 hours - if persisent consider need for antifungal therapy
• Antibiotics may be stopped when the patient has responded to treatment - irrespective of neutrophil count

Question 10

Neutropaenia - Infection Prevention

Answer 10

• Prophylactic antibiotics
  
  • Ciprofloxacin given for duration of neutropaenia
• Protective (reverse) isolation
  
  • Decrease nosocomial risk with:
    
    • Single room with HEPA-filtered air
    • Handwashing critical
  • Minimise exposure to potential exogenous pathogens
    
    • Neutropaenic diet
• Granulocyte colony-stimulating factor (G-CSF)
  
  • Not used routinely
• Approaches to reduce catheter-related infection

Question 11

Impaired Cellular Immunity

Answer 11

• Cellular immunity = T-lymphocyte mediated
• Defects may be:
  
  • Acquired
    
    • Drugs eg. cytotoxic chemotherapy, steroids
    • Radiation
    • Lymphoma
    • Hematopoietic stem cell transplantation
    • Infections eg. HIV
  • Congenital
• May lead to infections that are:
  
  • Opportunistic
  • Intracellular
  • Emergence of latent infection or reactivation

Question 12

Impaired Cellular Immunity - Viral Infections

Answer 12

• Herpes simplex virus
• Varicella zoster virus
• Cytomegalovirus
• Epstein-Barr virus
• Respiratory viruses

Question 13

Impaired Cellular Immunity - Bacterial Infections

Answer 13

• Listeria monocytogenes
  
  • ​Occasional cause of severe meningitis
• *Nocardia *species
  
  • May manifest as pneumonia or lung nodules
• *Mycobacterium *species
  
  • Non-tuberculous mycobacteria may cause:
    
    • Line-related infections
    • Bacteraemia
    • Pneumonia
  • *M.tuberculosis *occurs predominantly in countries with high endemic rates

Question 14

Impaired Cellular Immunity - Fungal Infections

Answer 14

• Pneumocystis jirovecii
  
  • ​Sx - dyspnoea, cough, fever, bilateral infiltrates
  • Treat with co-trimoxazole
• *Aspergillus *species
  
  • Commonly affects lungs and sinuses
• Cryptococcus neoformans
  
  • Frequent cause of meningitis in HIV-infected patients

Question 15

Impaired Cellular Immunity - Parasitic Infections

Answer 15

• Toxoplasma gondii
  
  • May present as:
    
    • Fever
    • Encephalitis with focal cerebral lesions
    • Pneumonitis
    • Myocarditis
• *Cryptosporidium *species
  
  • Mary lead to chronic or severe disease

Question 16

Impaired Cellular Immunity - Diagnosis and Treatment of Infections

Answer 16

• Diagnosis:
  
  • Pathogen appropriate clinical features
  • Ceulture
  • Serology
  • Biopsy/histology
  • Molecular tools eg. EIA, PCR
• Treament:
  
  • Appropriate to pathogen
  • Empiric

Question 17

Impaired Cellular Immunity - Infection Prophylaxis

Answer 17

• May be:
  
  • Primary
    
    • HIV infection when CD4 count is <200 cells/mm³
  • Secondary
• Defined refimens in HIV and hematopoietic stem cell transplantation (HSCT)

Question 18

Impaired Humoral Immunity and Complement Deficiency

Answer 18

• Mediated by B-lymphocytes
• May be:
  
  • Primary - congenital
  • Secondary - acquired
    
    • Lymphoproliferative disorders
      
      • eg. Chronic lympocytic leukaemia, multiple myeloma
    • Hypo/asplenism
      
      • Splenectom
      • Sickle cell disease
    • Anti-cancer treatment
      
      • Cytotoxic chemotherapy
      • Radiotherapy
      • Hematopoietic stem cell transplantation
    • Drugs
    • Protein defiency
      
      • Protein-losing enteropathy
      • Nephrotic syndrome
      • Burns

Question 19

Impaired Humoral Immunity and Complement Deficiency - Infectious Pathogens

Answer 19

• Bacteria
  
  • Encapsulated bacteria:
    
    • Streptococcus pneumoniae
    • Haemophilus influenzae
    • Neisseria meningitidis
  • *​**Capnocytophage canimorsus *- from animal bites
• Parasites
  
  • Malaria
  • Babesiosis

Question 20

Impaired Humoral Immunity and Complement Deficiency - Presentation

Answer 20

• Congenital
  
  • Usually presents with recurrent acute respiratory tract infections
    
    • Sinusitis
    • Otitis media
    • Pneumonia
      
      • May ==> to chronic disease
• Acquired (eg. postsplenectomy sepsis)
  
  • Fever/rigors
  • Fulminating infection

Question 21

Impaired Humoral Immunity and Complement Deficiency - Management

Answer 21

• Treatment
  
  • Antibiotics for infection
  • Identify underlying problem and correct
    
    • Immunoglobulin replacement
• Prevention
  
  • Prophylactic antibiotics
    
    • Penicillin V
  • Vaccines
    
    • Pneumococcal
    • Meningococcal
    • Hib
    • Influenza