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Multisystems > Micro- Infections in Recipients of Solid Organ Transplantation > Flashcards

Micro- Infections in Recipients of Solid Organ Transplantation Flashcards

1
Q

What is presensitization for SOT?

A

when the transplant recipient has a high number of preformed circulating anti-HLA antibodies leading to increased risk of rejection of the transplanted organ

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2
Q

What do antiproliferative agents used for immunosuppression do?
Which drugs are anti-proliferatives?

A

Anti-proliferative drugs inhibit purine synthesis which limits B and T cell division and proliferation blunting CELL-MEDIATED immunity

  1. azathioprine
  2. Mycophenolate Mofetil [MMF]
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3
Q

What is the mechanism of action of MMF?

What 2 infections does it put patients at an increased risk for?

A

It is inosine monophosphate dehydrogenase inhibitor which disrupts de novo purine synthesis

[disrupts guanine synthesis]

It puts patients at increased risk for:

  1. BK nephropathy
  2. CMV
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4
Q

How do corticosteroids cause immunosuppression?

A

They block T-cell and APC cytokine expression:

  1. impairing T-cell activation/proliferation [IL-2]
  2. inhibiting inflammatory response [IL-1]
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5
Q

What is the ultimate result of using corticosteroids?

A
  1. lymphocytopenia, monocytopenia, neutrophilia

2. antibody suppression only occurs at high doses for long periods of time

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6
Q

What is the MOA of polyclonal anti-lymphocyte antibodies?

A

Opsonize leukocytes and platelets and elicit immune suppression via T-cell inactivation

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7
Q

For how long does lymphopenia last after giving a patient polyclonal anti-lymphocyte antibodies?
What syndrome can be caused by this?
What infections are patients at an increased risk for?

A

lymphopenia lasts for a year and has increased infection risk for over 3 months after administration.

Cytokine release syndrome due to ativation of T-cell before it is destroyed:
fever, chills, pulm edema, aseptic meningitis

Increased risk of:

  1. viral infection
  2. lymphoid malignancy
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8
Q

What are the 2 main polyclonal anti-lymphocyte antibodies?

A
  1. ATG [anti-thymocyte globulin] = rabbit

2. ATGAM [anti-human thymocyte globulin] = equine

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9
Q

What are the 5 monoclonal antibodies used in host immunosuppression?
What specifically do they each attack?

A
  1. OKT3 = anti-CD3
  2. Basiliximab, Daclizumab = anti CD25
  3. Alemtuzumab = anti CD52
  4. belatacept = CTLA4-Ig complex that binds to APCs
  5. rituximab = anti CD20
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10
Q

What is the MOA of OKT3?

What is the major side effect?

A

It is anti-CD3 and depresses T-cells via TCR transduction blockade

[Does not allow activation of T-cells]

SIDE EFFECT = cytokine release syndrome

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11
Q

What is MOA of basiliximab, daclizumab?

A

They are anti CD-25 so they block IL-2R inhibiting clonal proliferation and differentiation of activated T cells.

  • no cytokine storm
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12
Q

What is the MOA of alemtuzumab? What is the major side effect?

A

It is anti-CD52, so it binds T, B, NK, monocytes and macrophages that have CD52.

This leads to Ab-dependent, cell-mediated lysis.

Side effect: neutropenia

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13
Q

What is the MOA of rituximab?

What is it specifically used for?

A

It is anti-CD20 and targets B cell lymphocytes.

It is used to reduce presensitization

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14
Q

What is the MOA of calcineurin inhibitors?

What are the 2?

A

Block calcineurin and inhibit T-cell activation and IL-2 production

  1. Cyclosporine
    - isolated from tolypocladium
  2. tacrolimus
    - isolated from streptomyces
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15
Q

What is the MOA of mTOR inhibitors?
How do they compare to calcineurin inhibitors?
What is the main example?
What 2 side effects?

A

They inhibit mTOR thus blocking G0 to G1 transition and G1-S phase of T-cell activation.

They are more selective than CIs.

Sirolimus

Side effects: delayed wound healing, oral ulcers

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16
Q

What 4 factors affect risk of infection in SOT?

A
  1. time period after transplant
  2. type of transplant
  3. pre-transplant exposure
  4. donor-derived infections
17
Q

What factors contribute to a patients “net state of immunosuppression”?

A
  1. type, dose, timing of immunosuppressive meds
  2. Immunomodulatory viruses:
    - CMV, EBV, HIV, HBV, HCV
  3. diabetes or renal insufficiency
18
Q

What epidemiologic exposures affect a patients risk of infection post-transplant?

A
  1. nosocomial vs. CA
  2. exposure pre and post transplant
  3. prophylaxis
19
Q

What is given as prophylaxis if the patient has:

  1. CMV
  2. PCP
  3. Fungal infection
  4. TB
A
  1. ganciclovir/valganciclovir
  2. TMP- SMX or [dapsone, atovaquone, inhaled pentamide]
  3. nystatin, fluconazole, ampho B
  4. pyridoxine, isoniazid
20
Q

What are the 3 most common infections that occur in the first month after SOT?

A
  1. Nosocomial infections predominate
    - ventilator pneumo, CVC bacteremia, UTIs
  2. Bacterial & Candida from surgical technique and post-op care
  3. donor-derived infection
21
Q

What time period after SOT has the highest net state of immunosuppression?

A

1-6 months

22
Q

What infections are most common in the intermediate post-transplant stage [1-6 months]?

A
  1. viral reactivation - CMV, EBV, HBV, HCV
  2. opportunistic infections
    - aspergillus
    - Cryptococcus
    - nocardia
    - listeria
    - t. gondii
23
Q

What causes reactivation of CMV during intermediate posttransplant stage?

A

discontinuation of gangiclovir prophylaxis

24
Q

What type of infection predominates the late post-transplant stage [over 6 months]?

A

community-acquired infections because not the patient is at home with a good allograft and minimal suppression.

  1. Viral respiratory infections: Flu, parainfluenza, RSV, adenovirus, human metapneumovirus
  2. bacterial respiratory infections: legionella, pneumococcus
25
Q

Which organ when transplanted has the lowest number of incidence of infection with scarce deep fungal infection?

A

Renal

26
Q

What infection is most associated with renal transplant?

A
  1. UTIs

2. pyelonephritis [if within the first 3 months, reduced graft survival]

27
Q

What type of transplant carries the highest risk of bacteremia and the second highest rate of deep fungal infections?

A

Liver transplant

28
Q

What types of infections predominate liver transplants?
What are the infections related to?
What organisms are most present?

A
  1. biliary tract
  2. abdominal

These infections are related to surgical complications like:
abscesses, peritonitis, cholangitis

Enteric G-, enterococci, anaerobes, staph, candida

29
Q

What increases the risk of bacterial infection with liver transplant?

A
  1. prolonged surgery duration
  2. multiple transfusions
  3. repeated transplants
  4. CMV
30
Q

What increases the risk of a deep fungal infection post liver transplant?

A
  1. elevated Cr
  2. long surgery
  3. repeated transplant
  4. Fe overload
  5. candida
31
Q

Which organ transplant has the highest rate of infection OVERALL? Why?

A

Heart-Lung or Lung

  1. decreased mucocililary clearance
  2. decreased lymphatic drainage
  3. absent cough reflex
  4. environmental exposure
  5. ischemia at anastomoses
  6. allograft rejection –> bronchiolitis obliterans
32
Q

Which transplant has:

  1. second highest rate of bacteremia
  2. highest rate of mediastinitis
  3. highest rate of deep fungal infections
  4. highest rate of CMV reactivation
  5. highest mortality from infection?
A

lung

33
Q

What is bronchiolitis obliterans syndrome?

A

Chronic allograft rejection with decreased FEV1

34
Q

What infections predominate with heart transplants?

A
  1. lung infections

2. endocarditis within the first month

35
Q

With a heart transplant, what infectious agents are associated with mediastinitis and sternal wound infections?

A
  1. s. aureus

2. s. epidermitis [coag neg staph]

36
Q

What 4 infections can occur in heart transplants?

A
  1. mediastinitis, sternal wound = staph aureus, coag neg staph
  2. Toxo from infected donor
  3. nocardiasis
  4. chaga’s - reactivation of T. cruzi
37
Q

What 10 things are studied for pre-transplant history for the recipient?

A

1, HSV

  1. CMV
  2. EBV
  3. HBV
  4. HCV
  5. RPR [syphilis]
  6. VZV
  7. T. gondii
  8. TB
  9. HIV
38
Q

What tests are done on donors to see if they are eligible to donate organs?

A
  1. HIV 1/2, PCR to “catch” window period
  2. RPR/VDRL
  3. HepB
  4. Hep C
  5. EBV
  6. CMV
  7. tracheal swabs for lung transplants
  8. urine/blood culture if febrile or with leukocytosis

Multisystems (29 decks)

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