Opportunistic Infections in Solid-Organ Transplantation Flashcards
The Immunocompromised Host: Extremely Complicated
T2DM
Liver Dx, CKD
Biologics Use
Severe,
prolonged
neutropenia
Very uncontrolled HIV
SOTRs/HSCTRs
“Immunocompromised” – Oversimplifying A Complex Problem
Increased Susceptibility
E.g., uncontrolled T2DM, chronic
kidney or liver disease, solidorgan tumors not on
chemotherapy, burn victims, etc.
Increased chance of NORMAL
infections compared to healthy
population, does not get
atypical or strange infections
with uncommon organisms
Specific Deficiency
E.g., patients on biologics,
patients with controlled HIV,
those with structural lung disease
Increased chance of NORMAL
infections compared to healthy
population, are susceptible to
CERTAIN infections with
uncommon organisms (e.g., TB,
endemic fungi)
Truly Immunocompromised
E.g., post-SOT, post-stem cell
transplant, severely
uncontrolled HIV, severe bone
marrow suppression
Increased chance of ATYPICAL
infections with organisms THAT
DON’T USUALLY CAUSE
DISEASE and increased chance
of severe but normal infections
I
Be specific about the extent/severity of your patient’s immunodeficiency to properly assess for infectious diseases!
Opportunistic Infections in Solid-Organ Transplantation
Infections that occur in solid-organ transplant recipients (SOTRs) are
challenging to manage, and a whole infectious diseases sub-specialty
is devoted to their care (transplant infectious diseases).
Management is difficult for several reasons:
1. May be more severe, progress more rapidly
2. May be more difficult to recognize
a. Immunosuppression may blunt inflammatory response
b. Use of steroids may mask fever/inflammatory response
c. Surgical alterations in anatomy may hinder recognition
d. Non-infectious causes often mimic infection
a. E.g., steroid-induced leukocytosis
b. Allograft rejection & graft-versus-host disease
3. DDIs between immunosuppression and antimicrobials
Infections in SOTRs often involve transplant infectious diseases, an ID subspecialty branch
Risk Factors for Infection in Solid-Organ Transplantation
Donor Factors
Latent infections
Unrecognized
active illness in
donor
Recipient Factors
Underlying illness
Age
Vaccination status
Allograft organ
(++ infx @ graft)
Intra-Operative
Factors
Surgical procedure
Ischemic injury and
OR duration
increases
contamination risk
Post-Operative
Factors
Immunosuppression
Technical problems
affecting allograft
Foreign devices
Hospital exposure
There are many predisposing factors OTHER than immunosuppressive medications!
The Most Important Reason for Compromise
T-CELL DEPLETION
* In SOTRs – patients receive T-cell depleting agents to
substantially reduce the risk of rejection – aka. Rabbit
antithymoglobulin (rATG) or basiliximab which severely
affect T-cell function
* In stem-cell transplant recipients – patients usually have a
bone marrow cancer – so are given myeloablative
chemotherapy to wipe out all of their bone marrows stemcells and malignant cells
Some patients T-cells never completely recover – but in those
who do – recovery is delayed but generally around 1-2 years!
T-cell depletion more than any other feature is responsible for the extent of compromise.
Relative Immunosuppression & Risk Post-SOT
early period
intermediate period
late period
Immune function waning
Possible donor derived OR hospital
acquired infection
Immunosuppression often REDUCED
Decreased risk of OI compared to
intermediated period, but higher baseline
risk of OI compared to general population
Peak of immunosuppression. OI risk is
the highest
Timing of Infection & Solid-Organ Transplantation
Early Period
Nosocomial bacterial
infections (e.g., line-related
infx, CA-UTI, wounds,
ventilator-associated PNA,
C. difficile colitis)
Intermediate Period
M. tuberculosis or nontuberculous mycobacterial
infections
Viral Reactivation/Infection
Herpesviruses (HSV, VZV,
CMV, EBV)
BK virus
Fungal Infection
Pneumocystis jirovecci (PJP)
C. neoformans
Late Period
M. tuberculosis or nontuberculous mycobacterial
infections
Late Viral OI
Late CMV infection
M. tuberculosis or nontuberculous mycobacterial
infections
Late Fungal Infection
Invasive Aspergillosis
Other mold infections
Why These Weird Organisms? Why Now?
With few exceptions (e.g., very poorly controlled HIV, HSCT), the opportunistic infections (OI) that occur in
SOTRs are unique to SOTRs. So why don’t these occur in otherwise healthy people?
The primary defect responsible is the loss in the cellular branch of the adaptive immune system,
predominantly T-cell mediated. This is often accomplished through use of anti-thymocyte globulin or other
T-cell depleting immunosuppressive induction regimens.
Loss of cellular immune response is the primary defect explanatory for OIs with these organisms.
The Importance of T-Cells in Infectious Diseases
Intracellular pathogens are hard to eradicate since they can hide within host-cells (e.g.,
viruses, mycobacteria). The loss of T-cell functions predisposes to infection with these
organisms, as well as those who require T-cell assistance to activate innate responses (e.g.,
PJP, fungal organisms, mycobacteria as well)
Patient Case #1: Early Infections in Solid-Organ Transplantation
55-year-old female with chronic bronchiectasis who
received a bilateral sequential lung-transplant (BSLTx) 6-
days ago (POD6) from a deceased donor. Today she is
febrile (T 39.1°C) and has developed increased secretions
on mechanical ventilation. A CXR is ordered, which
reveals new multifocal airspace opacities concerning for
PNA.
Pre-operatively, the recipient was colonized with MDR
Pseudomonas aeruginosa with the following
sensitivities. The donor graft microbiology is still
pending. A bronchoscopy sample is taken for culture.
Q: What organisms do we treat in this case?
CONSIDER: Does the past microbiology of explanted organs still play a role in this infection?
Early Infections in Solid-Organ Transplantation
Predominantly hospital-acquired infections related to
surgery, procedural intervention, foreign device
installation and exposure to nosocomial pathogens by
healthcare staff.
Immune system functionally intact
Infection-rates post-operatively are not equally
distributed across allograft types:
* In general, organs that are contain a larger bacterial
burden and higher lymph organ burden (e.g., the
LUNG, the intestines) contribute to a higher
infectious burden than others (e.g., kidneys, heart)
Early infections (month 1) are less related to immunosuppressive regimens than later infections.
Hospital-Acquired Infections
EXAMPLE CASE:
36M admitted for BSLTx and is POD13 (post-op day #13). The
patient was recovering well and becoming ready for discharge
until the nurse alerts you to a new fever (38.5°C) and a
leukocytosis (WBC 14.1 up from 8.1).
Q: What infections should you be looking for?
* A head-to-toe infection approach is prudent, although some
infections are more likely in the hospital than others (i.e.,
unlikely to have developed a STI, for example)
When sick patients are admitted to the hospital for a prolonged
period of time, their risk of hospital-acquired infections
increases. We already discussed how some organisms are mostly
relevant as nosocomial pathogens.
Check for hospitalacquired PNA
(uncommon)
Assess for
catheter-related
UTI (if Foley in
place)
Assess for linerelated
bloodstream
infection (common,
especially with
central IV catheters)
Assess for C.
difficile (CDI) even
if not on antibiotics
(other risk factors)
Patient Case #1 Revisited: Early Infections in Solid-Organ Transplantation
Case continued…
The donor’s bronchoscopy results return, demonstrating
the following microbiology results.
The patient’s microbiology results (day 6 bronchoscopy
and bronchoalveolar lavage) return positive for
Pseudomonas aeruginosa (susceptibility pending).
PEARL: Past microbiology despite explantation may still be relevant in early post-SOT infection.
Q: What are the possible explanations for this patient’s
microbiology results?
Q: What is a reasonable empiric antibiotic regimen for
this patient with ventilator-associated PNA?
the nuance point in lung transplants is that, despite the fact that they actually transplant your lungs and remove both sets of your lungs and give you 2 new longs.
They keep your trachea in a lung transplant, and if you’re colonized with bacteria in your lungs, patients are often colonized all the way up their trachea and into their mouth. And so we know that when patients are colonized with organisms pre transplant, and then have those organs expplanted.
Unfortunately, they just colonize their new set of lungs, no matter what organisms were in there.
a big problem is when patients have a spurgeless or tuberculosis pre-transplants, because we know we’re just going to give their new set of lungs the same organism. So we end up having to deal with that contraction later on as well. So it’s no surprise. They still grow this pseudomonus in their day. 6 bronc.
They’re not growing. The steno, however. despite it being in the donor microbiology. So my empiric regimen would only be covering this pseudonymous.
Patient Case #2: The Intermediate Period in Solid-Organ Transplant
55-year-old female with chronic bronchiectasis who
received a bilateral sequential lung-transplant (BSLTx) 3
months prior, on a maintenance immunosuppression
regimen of TAC + MMF. She is being followed up as an
outpatient for routine bloodwork and antimicrobial
prophylaxis.
Donor: CMV IgG+ // Recipient: CMV IgGYou notice on her routine bloodwork that over the past 2
weeks her WBC count has been falling and is now 0.3 x
109/L.
Q: What – if any – drug-induced explanations are
there for this neutropenia? What is your action plan?
CONSIDER: What type of drugs are being used in this patient post-SOT?
Cytomegalovirus (CMV). AKA HHV5
Structure & Nucleic Acid
Group II (dsDNA) virus
* Icosahedral, enveloped (easy to destroy)
Epidemiology
* Ubiquitous (prevalent worldwide)
* Seropositivity (IgG+) ~ equal to age (e.g., ~50%
of people have been exposed @ age 50 years)
Transmission
* Usually shared by direct contact with blood or
bodily fluids (e.g., sharing drinks/sexual/oral)
* Also shared vertically (possible, but not
guaranteed transmission of virus)
Structure & Nucleic Acid
HHV-5
CMV
Cytomegalovirus
Attachment/Infectious Site
Predominantly mucosal
epithelium
Latency Site (Tropism)
Myeloid cells
(e.g., WBCs)
