approach to fever in the transplant patient

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

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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

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Page 1: Approach to fever in the transplant patient

Approach to fever in the transplant patientApproach to fever in the transplant patient

Farooq Khan MDCMPGY2 FRCP-EMMcGill UniversityJanuary 6th 2011

Page 2: Approach to fever in the transplant patient

Causes of fever in this population

Causes of fever in this population

InfectionRejection/GvHDMalignancyDrug feverHypersensitivity reactionThromboemobolic disease

InfectionRejection/GvHDMalignancyDrug feverHypersensitivity reactionThromboemobolic disease

Page 3: Approach to fever in the transplant patient

Surviving sepsis …Surviving sepsis …

Treat infections earlyChoose the right therapyCover for the right agentAnticipate which agents are

responsible

Treat infections earlyChoose the right therapyCover for the right agentAnticipate which agents are

responsible

Page 4: Approach to fever in the transplant patient

ConsiderationsConsiderations

Epidemiologic exposures Patient’s net state of immune

suppressionTime from transplantationType of transplantation Immune response is blunted,

anatomy is altered, so signs and symptoms are subtle and atypical

Epidemiologic exposures Patient’s net state of immune

suppressionTime from transplantationType of transplantation Immune response is blunted,

anatomy is altered, so signs and symptoms are subtle and atypical

Page 5: Approach to fever in the transplant patient

Epidemiologic exposuresEpidemiologic 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

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

Page 6: Approach to fever in the transplant patient

Exposures …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.

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.

Page 7: Approach to fever in the transplant patient

Net state of immune suppression

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)

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)

Page 8: Approach to fever in the transplant patient

Time after transplantationTime 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

<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

Page 9: Approach to fever in the transplant patient

Time after transplantationTime 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

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

Page 10: Approach to fever in the transplant patient

Time after transplantationTime 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

> 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

Page 11: Approach to fever in the transplant patient

Type of transplantType 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

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

Page 12: Approach to fever in the transplant patient

Physical exam elements often forgotten

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!

Oral mucosa Retina, sinuses Skin Neuro exam Dialysis catheters Rectal Think altered anatomy Don’t just examine the CV, Resp, and

Abdo!

Page 13: Approach to fever in the transplant patient

Lab tests that can be useful

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!

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!

Page 14: Approach to fever in the transplant patient

General principles of management

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)

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)

Page 15: Approach to fever in the transplant patient

General principles of management

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)

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)

Page 16: Approach to fever in the transplant patient

ReferencesReferences

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 recipientAuthor Jay A Fishman, MD Section Editor Peter F Weller, MD, FACP Deputy Editor Anna R Thorner, MDhttp://www.uptodateonline.com/online/content/topic.do?topicKey=immuninf/2303&selectedTitle=3~150&source=search_result Last literature review version 16.2:May 2008 

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 recipientAuthor Jay A Fishman, MD Section Editor Peter F Weller, MD, FACP Deputy Editor Anna R Thorner, MDhttp://www.uptodateonline.com/online/content/topic.do?topicKey=immuninf/2303&selectedTitle=3~150&source=search_result Last literature review version 16.2:May 2008