Quick Approach to solid organ transplant patients presenting to the ED with fever to guide initial work-up and managment. Audience: Medical students and junior residents in a small group environment

1. Approach to fever in the
transplant patient
Farooq Khan MDCM
PGY2 FRCP-EM
McGill University
January 6th
2011

2. Causes of fever in this population
Infection
Rejection/GvHD
Malignancy
Drug fever
Hypersensitivity reaction
Thromboemobolic disease

3. Surviving sepsis …
Treat infections early
Choose the right therapy
Cover for the right agent
Anticipate which agents are
responsible

4. Considerations
Epidemiologic exposures
Patient’s net state of immune
suppression
Time from transplantation
Type of transplantation
Immune response is blunted, anatomy
is altered, so signs and symptoms are
subtle and atypical

5. Epidemiologic exposures
 Community acquired pathogens (Ask about contacts,
geography, socioeconomic status, occupation)
 Common things are common!
 Respiratory viruses (flu, paraflu, rsv, adeno)
 Bacteria (strep, staph, mycoplasma, listeria, salmonella)
 Endemic fungi (histoplasma, cryptococcus, aspergillus,
cryptosporidia)
 Reactivation of infection in patient (Were they known
carriers? Were they immunized?)
 HSV, CMV, VZV, HBV, HCV, HPV
 TB, fungi, parasites
 Nosocomial infection (Ask about recent
hospitalizations, previous antibiotic therapy)
 MRSA, VRE, C diff
 Legionella, pseudomonas, candida

6. Exposures …
 Donor derived infection (Where did the graft
come from?)
 Donor had a bloodstream infection (E. coli,
salmonella, strep, staph, candida) that sticks to
anastomotic sites in graft recipient
 CMV, EBV – seropositive donors
 TB, histoplasma - can reactivate years later
 HIV, HTLV, hepatitis - may be missed by
screening
 Wild and wonderful stuff (Ask about travel
and animals!)
 Leishmania, strongyloides, dengue, trypanosoma,
West Nile, rabies, toxoplasma, ehrlichiosis,
LCMV… Etc.

7. Net state of immune suppression
 Type, dose, timing of immunosuppressive
therapy (Look up the meds)
 Recent/repeated rejection episodes usually mean
an increase in anti-rejection meds dose
 Level of neutropenia/lymphopenia
 Underlying disease or comorbidity (PMH)
 Including malnutrition, diabetes, uremia, HIV
 Invasive catheters, drains, hardware (Do a
full physical)
 Presence of devitalized tissue or fluid
collections (Don’t be afraid to look under that
dressing or get that CT)

8. Time after transplantation
 <1 month (post-op infections, high resistance
rates)
 Nosocomial infections (MRSA VRE Candida c.
diff)
 Aspiration
 Catheter related
 Wound infection
 Anastomotic leak / abscess / ischemia
 Donor derived (rare) – HSV, CMV, HIV,
trypanosoma, west nile
 Recipient derived 2° to colonization with
aspergillus or pseudomonas

9. Time after transplantation
 1-6 months (highest risk of rejection→highest
level of immune suppression→highest rate of
opportunistic infection)
 Without prophylaxis
 PCP, Herpesviruses (HSV, VZV, CMV, EBV) HBV
 Listeria, nocardia, toxoplasma, strongyloides,
leishmania, trypanosoma
 With prophylaxis
 HCV, cryptococcus, TB, C. diff, respiratory
viruses, polyomavirus BK
 Anastomotic complications

10. Time after transplantation
> 6 months (stable levels of immune
suppression, community acquired
pathogens, late viral infection,
malignancy)
CAP, UTI, Aspergillus, other molds,
mucor, nocardia
CMV (colitis, retinitis) hepatitis, HSV
encephalitis, SARS, West nile
PML, lymphoma, skin cancers

11. Type of transplant
 Heart: mediastinitis, peri/myo/endocarditis
 Staph aureus, staph epi
 Lung: pneumonia, empyema
 CMV, PCP, pseudomonas
 Liver: cholangitis, intraabdominal abscess,
hepatic abscess, peritonitis
 Gram -, enterobacter, enterococcus, candida
 Renal: UTI/Pyelo, bacteremia
 Gram-, candida

12. Physical exam elements often
forgotten
 Oral mucosa
 Retina, sinuses
 Skin
 Neuro exam
 Dialysis catheters
 Rectal
 Think altered anatomy
 Don’t just examine the CV, Resp, and Abdo!

13. Lab tests that can be useful
 Pancultures (mouth, urine, stool, blood,
sputum, access, wound, fluid drainage)
(include virology and fungal cultures)
 Antigen-based tests are more useful than
serologic tests (Go ELISA or PCR)
 Medication levels (e.g. cyclosporin,
tacrolimus)
 Test organ function (liver, renal, pulmonary,
echo, EKG, chest x-ray..) (may deteriorate
rapidly in rejection)
 Remember, signs and symptoms are limited.
Be generous!

14. General principles of
management
Low threshold for imaging due to lack
of clinical manifestations of infection
(Argue with the radiologist for that CT if
you have to)
May need invasive diagnostic
procedures to obtain tissue for culture
and histology to rule out rejection (Get
your surgeons involved)

15. General principles of
management
 Resistant organisms are common due to
hospital environments and prolonged
antimicrobial therapy (Hit hard, go broad)
 Be mindful of drug toxicities and interactions
with choice of antimicrobial therapy (Check
with your (e-)pharmacist)
 Catheters, drains, blood clots, fluid
collections, devitalized tissue must be
removed or antimicrobials will fail (Think
source control)

16. References
 N. Singh et al. (eds .), Infectious Complications in
Transplant Recipients © Springer-Verlag US 2001,
Chapter 4 Post transplant fever in critically ill organ
transplant recipients
 Infection in the solid organ transplant recipient
Author Jay A Fishman, MD Section Editor Peter F
Weller, MD, FACP Deputy Editor Anna R Thorner,
MD
http://www.uptodateonline.com/online/content/topic.do?topi
Last literature review version 16.2:May 2008