Approach to fever in the transplant patient

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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

Published in: Health & Medicine, Education
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  •   Risk factors for infection should be carefully sought in all solid organ transplant (SOT) patients. The pre-transplantation history (eg, serologic status against microorganisms such as cytomegalovirus [CMV], hepatitis virus,  Toxoplasma , etc) may yield valuable information. Previous infections or colonization, exposure to tuberculosis, contact with animals, raw food ingestion, gardening, prior antimicrobial therapy or prophylaxis, vaccines or immunosuppressors, and contact with contaminated environment or persons should be recorded  [36] ,  [37] . History of residence or travel to endemic areas of regional mycosis  [38]  or tropical destinations must be considered in these patients because of potential emerging pathogens causing FUO such as dengue virus  [39], [40] or Strongyloides stercoralis [41]. Exposure to ticks may be essential to diagnose entities such as human monocytic ehrlichiosis, which may be potentially lethal in immunosuppressed patients 
  • Lymphocytic choriomeningitis, a zoonosis that is transmissable from hamsters, mice and other rodents to people ticks
  • Approach to fever in the transplant patient

    1. 1. Approach to fever in the transplant patient Farooq Khan MDCM PGY2 FRCP-EM McGill University January 6th 2011
    2. 2. Causes of fever in this population Infection Rejection/GvHD Malignancy Drug fever Hypersensitivity reaction Thromboemobolic disease
    3. 3. Surviving sepsis … Treat infections early Choose the right therapy Cover for the right agent Anticipate which agents are responsible
    4. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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 

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