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Week 7 - Clinical Microbiology & Infections 2 > Infections in the Immunocompromised > Flashcards

Infections in the Immunocompromised Flashcards

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1
Q

What are the components of the normal innate defence mechanisms of the immune system? [8]

A
  1. Skin
  2. Resident flora - colonisation resistance
  3. Complement
  4. Lysozyme
  5. Acute phase reactants
  6. Phagocytes (neutrophils & macrophages)
  7. Spleen
  8. NK cells
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2
Q

What does the normal adaptive immune response consist of? [4]

A
  1. Humoral response (producing antibodies)
    • B cells
  2. Cellular response
    • T cells
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3
Q

What are the functions of B cells? [3]

A
  1. Neutralisation
  2. Complement activation
  3. Opsonisation
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4
Q

What are the functions of T cells? [3]

A
  1. Help macrophages
  2. Help B cells
  3. Kill virus-infected cells
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5
Q

A compromised defence system leads to…? [3]

A

increased susceptibility to infection by conventional and opportunistic pathogens

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6
Q

Describe the 2 types of immunodeficiency [8]

A
  • primary
    • inherited
    • exposure in utero to environmental factors
    • rare
  • secondary
    • due to underlying disease
    • due to treatment of disease (chemotherapy)
    • common
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7
Q

Define neutropenia (incl. figures) [3]

A

abnormal decrease in the number of neutrophils in the blood

  • <0.5 x 109L or
  • <1.0 x 109L and falling
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8
Q

Describe the pathophysiology of the development of neutropenia [3]

A
  • Cytotoxic chemotherapy and therapeutic irradiation (TBI) causes decreased proliferation of haemopoietic progenitor cells.
  • This leads to a depletion of marrow reserves of neutrophils and other blood cells → eventually leading to neutropaenia
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9
Q

How does cytotoxic drugs, irradiation and steroids affect neutrophil function? [3]

A
  1. decreased chemotaxis
  2. decreased phagocytic activity
  3. decreased intracellular killing
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10
Q

What pathogens can cause neutropenia? [12]

  • hints:
    • gram positive cocci [4]
    • anaerobes [2]
    • gram negative bacilli [4]
    • fungi [2]
A
  • Gram positive cocci
    1. Staph. aureus
    2. Coagulase negative staphylococci
    3. Viridans streptococci (mitis, oralis)
    4. Enterococci (faecalis, faecium)
  • Anaerobes
    1. Bacteriodes spp.
    2. Clostridia spp.
  • Gram negative bacilli
    1. E. coli
    2. Pseudomonas aeruginosa
    3. Klebsiella pneumoniae
    4. Enterobacter spp.
  • Fungi
    1. Candida spp.
    2. Aspergillus spp.
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11
Q

Define chronic granulomatous disease [1]

A

an inherited primary immunodeficiency disorder (PIDD) which increases the body’s susceptibility to infections caused by certain bacteria and fungi

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12
Q

What is the primary genetic defect causing chronic granulomatous disease and what does this lead to? [3]

A
  1. Defect in gene coding for NADPH oxidase
    • deficient production of oxygen radicals
    • defective intracellular killing
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13
Q

What are the complications of chronic granulomatous disease [7]

A
  1. Recurrent bacterial & fungal infections
    • can lead to abscesses in lung, lymph nodes & skin
  2. Inflammatory responses with widespread granuloma formation.
  3. Pulmonary infection caused by:
    • Aspergillus spp.
    • Staph. aureus
    • Nocardia spp.
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14
Q

What factors can suppress cellular immunity? [7]

A
  1. DiGeorge syndrome (primary deficiency, rare)
  2. Malignant lymphoma
  3. Cytotoxic chemotherapy
  4. Extensive irradiation
  5. Immunosuppressive drugs
  6. Allogeneic stem cell transplantation
  7. Infections such as HIV, mycobacterial infections, measles, Epstein-Barr virus (EBV), Cytomegalovirus (CMV)
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15
Q

What is DiGeorge Syndrome? [1]

A

primary immunodeficiency disorder that results in T cell deficiency

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16
Q

Give examples of immunosuppressive drugs [6]

A
  1. corticosteroids
  2. cyclosporin (used to prevent organ rejection)
  3. tacrolimus (more potent than cyclosporin)
  4. alemtuzumab (anti-CD52 monoclonal)
  5. rituximab (anti-CD20 monoclonal)
  6. purine analogues e.g. fludarabine (causes profound lymphopenia)
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17
Q

What factors can suppress humoral immunity? [4]

A
  1. Bruton agammaglobulinemia (primary, rare)
  2. Lymphoproliferative disorders such as:
    • CLL (usually preserved in acute leukaemia)
    • multiple myeloma
  3. Intensive radiotherapy and chemotherapy will ultimately cause hypogammaglobulinemia
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18
Q

What are the normal functions of the spleen? [4]

A
  1. Splenic macrophages eliminate non-opsonized microbes
    • e.g. encapsulated bacteria
  2. Site of primary immunoglobulin response
    • specific opsonizing antibody required for phagocytosis of encapsulated bacteria
    • impairs activity of all phagocytic cells
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19
Q

Define colonisation resistance [1]

A

the mechanism whereby the normal microbiota protects itself against invasion by new and often harmful microorganisms

20
Q

What factors are present in the skin that makes it a poor environment for abnormal bacteria to grow? [5]

A
  1. Desquamates (flakes off - regenerates quickly)
  2. Dry
  3. pH = 5-6 (acidic)
  4. Temp = 5°C lower than what is ideal for bacterial growth
  5. Secretory IgA in sweat
21
Q

What is mucositis? [1]

A

painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer.

22
Q

Describe the pathophysiology of mucositis [4]

A

Cells in the mucosa of the gut and GU tract have a considerable high cell turnover rate (high mitotic index) and are exquisitely sensitive to insult, particularly chemotherapy and irradiation.

So they die quickly and this stimulates an immune response from GI lymphoid tissue leading to mucositis

23
Q

What are the symptoms of mucositis? [4]

A
  1. Pain
  2. Dysphagia (difficulty swallowing)
  3. Xerostomia (dry mouth)
  4. Ulceration
24
Q

What are the complications of mucositis? [3]

A
  1. Impairment of GI function
  2. Weakens the cellular barrier between the gut and the bloodstream (alterations in permeability)

This can lead to malnourishment (altered nutritional status)

25
Q

What is severe nutritional deficiency defined as? [2]

A
  1. <75% ideal body weight or
  2. rapid weight loss + hypoalbuminemia
26
Q

What are the complications of severe nutritional deficiency and what does this ultimately lead to? [5]

A
  1. Anorexia
  2. Nausea & vomiting
  3. Mucositis
  4. Metabolic derangements

ultimately leads to compromise in the integrity of host defences

27
Q

How can stress lead to people becoming immunocompromised? [1]

A

results in reduced T cell function

28
Q

How can diabetes lead to people becoming immunocompromised? [2]

A
  1. reduced opsonisation
  2. reduced chemotaxis
29
Q

Febrile neutropenia is a major complication of chemotherapy in cancer patients. What is it? [5]

A

Neutrophil count < 0.5 or < 1 x 109/L typically in patients with recent chemotherapy (usually within 10 days but can persist for up to 21 days)

PLUS

  • Fever/Hypothermia or
  • SIRS or
  • Sepsis/Septic shock
30
Q

What are the 3 most common pathogens that cause febrile neutropenia? [3]

A
  1. E. coli
  2. Klebsiella spp.
  3. Pseudomonas spp.

(mainly gram -ves, but gram +ves, anaerobes, fungi and viruses can also cause it)

31
Q

Define fever [3]

A
  • Pyrexia temperature > 38°C or Hypothermia < 36°C

OR

  • > 37.5°C on 2 occasions 30 minutes apart
32
Q

What are the symptoms of SIRS (Systemic Inflammatory Response Syndrome)? [9]

A
  1. sweats
  2. chills
  3. rigors
  4. malaise
  5. tachypnoea
  6. RR > 20/minute
  7. tachycardia HR > 90 bpm
  8. hypotension
  9. (Patients may appear well perfused despite hypotension)
33
Q

Define sepsis [2]

A
  • evidence of infection (including SIRS)

PLUS

  • organ dysfunction i.e.
    • ≥2 of hypotension, confusion or tachypnoea (RR ≥ 22/minute)
34
Q

Define septic shock [4]

A
  • sepsis induced hypotension requiring inotropic support

OR

  • hypotension that is unresponsive (within 1 hour) to adequate fluid resuscitation
    • i.e. systolic BP < 90mmHg or a reduction of >40mmHg from baseline
35
Q

What is the sepsis 6 care bundle that must be commenced immediately for a patient presenting with febrile neutropenia? [6]

A
  1. blood cultures (& any other relevant samples)
  2. antibiotic administration
  3. oxygen → to maintain target saturation
  4. measure lactate and haemoglobin
  5. IV fluids
  6. monitor urine output
36
Q

A patient who has not had a stem cell/solid organ transplant and are not receiving chemotherapy and does not have sepsis, septic shock or NEWS ≥ 7, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

STANDARD RISK

  1. IV piperacillin/tazobactam
  2. +/- IV vancomycin
37
Q

A patient who has not had a stem cell/solid organ transplant and are not receiving chemotherapy and does not have sepsis, septic shock or NEWS ≥ 7, but has a true penicillin/beta lactam allergy, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [2]

A

STANDARD RISK

  1. IV gentamicin
  2. AND IV vancomycin
38
Q

A patient who has not had a stem cell/solid organ transplant and are not receiving chemotherapy but has sepsis, septic shock or NEWS ≥ 7, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

HIGH RISK

  1. IV piperacillin/tazobactam
  2. AND IV gentamicin
  3. AND IV vancomycin
39
Q

A patient who has not had a stem cell/solid organ transplant and are not receiving chemotherapy but has sepsis, septic shock or NEWS ≥ 7, AND has a true penicillin/beta lactam allergy, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

HIGH RISK

  1. IV gentamicin
  2. AND IV vancomycin
  3. AND IV ciprofloxacin
40
Q

A patient who has had a stem cell/solid organ transplant or are receiving chemotherapy for acute leukaemia but does not have sepsis, septic shock or NEWS ≥ 7, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

HIGH RISK

  1. IV piperacillin/tazobactam
  2. AND IV gentamicin
  3. AND IV vancomycin
41
Q

A patient who has had a stem cell/solid organ transplant or are receiving chemotherapy for acute leukaemia but does not have sepsis, septic shock or NEWS ≥ 7, but does have a true penicillin/beta lactam allergy, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

HIGH RISK

  1. IV gentamicin
  2. AND IV vancomycin
  3. AND IV ciprofloxacin
42
Q

A patient who has had a stem cell/solid organ transplant or are receiving chemotherapy for acute leukaemia AND has sepsis, septic shock or NEWS ≥ 7, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

CRITICAL RISK

  1. IV meropenem
  2. AND IV amikacin
  3. AND IV vancomycin
43
Q

A patient who has had a stem cell/solid organ transplant or are receiving chemotherapy for acute leukaemia AND has sepsis, septic shock or NEWS ≥ 7, AND has a true penicillin/beta lactam allergy, presents with febrile neutropenia.

Which antibiotics would you use to treat them? [3]

A

CRITICAL RISK

  1. IV amikacin
  2. AND IV vancomycin
  3. AND IV ciprofloxacin
44
Q

If a patient with febrile neutropenia is MRSA colonised or has a suspected central line infection or has signs of skin/skin tissue infection, what antibiotic must you give? [1]

A

IV vancomycin

45
Q

If a patient with febrile neutropenia has suspected community acquired pneumonia and atypical cover is required, what antibiotic must you give? [1]

A

IV clarithromycin

46
Q

If a patient with febrile neutropenia has a history of true penicillin/beta lactam allergy with suspected intra-abdominal sepsis, what antibiotic must you give? [1]

A

IV metronidazole

47
Q

If a patient with febrile neutropenia has had a previous ESBL infection or is a known ESBL carrier, what antibiotic must you give? [1]

A

replace piperacillin/tazobactam with carbapenem

Week 7 - Clinical Microbiology & Infections 2 (16 decks)

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