Overview
Although fever (T > 38.0) should usually prompt workup in patients with solid organ transplants, it is important to remember that these patients will frequently not manifest the classical signs, symptoms, and radiographic findings of infection until late in their course of illness. Therefore, one should perform a very thorough evaluation, taking even minimal abnormalities seriously. Risk for infection depends on the organ transplanted, the immunosuppressive regimen used, the development and treatment of GVHD and rejection, time since transplantation, use of prophylaxis, presence of comorbid illnesses, and epidemiologic exposures.
Etiology
- FUOs in transplant patients: CMV, EBV (post-transplantation lymphoproliferative disorder), HHV-6. Less commonly, PCP (with normal CXR), and surgical site abscess. See section Candidemia for risk factors. Less commonly, disseminated cocci, histo, TB (with history of exposure). Unusual donor related infections are also possible especially early after transplant. Non-infectious causes of fever include allograft rejection or medication effects.
- Infection by time period: below is the classic teaching, with the period of peak immunosuppression and the highest risk for opportunistic infections between 1-6 months post-transplant. Changes in immunosuppression such as treatment for rejection can reset the timeline. Prophylaxis against infection like CMV can result in later onset of disease. This timeline is a rough guide and opportunistic infections often present after 6 months as well.
- Month 1: nosocomial infections (surgical site infections, HAP, CRBSI, C. difficile, etc.) and donor-derived infections.
- Months 2-6: opportunistic infections and reactivation of latent infections such as CMV, EBV, candida, cryptococcus, invasive aspergillosis, PCP, nocardia, endemic mycoses, protozoal diseases, TB, herpes viruses, hepatitis B and C, BK virus, and others. Clinical signs and symptoms may be muted and radiographic evidence of infection less apparent on plain films.
- Month 6 and beyond: community-acquired infections (e.g. pneumococcus, respiratory viruses); can also see reactivation of latent infections. The risk of opportunistic infections decreases over time but can be present after treatment for rejection.
Evaluation
- Strongly consider a transplant ID consult in all solid organ transplant recipients who present with suspected infection.
- Begin with a standard evaluation: CBC with diff, LFTs, Cr, UA, blood and urine cultures, respiratory viral PCR testing (if considering upper or lower tract respiratory illness), etc.
- High risk patients (<4-6 months post-transplant or recently treated for acute rejection) or clinical suspicion for CMV disease (lymphadenopathy, hepatitis, pneumonitis, GI disease, chorioretinitis, etc.): send serum CMV PCR; may require further invasive studies such as LP or colonoscopy with biopsy.
- Consider early CT or MRI directed at localizing symptoms e.g., cough.
- May need more invasive diagnostics earlier than immunocompetent patients (e.g. bronch, tissue biopsy).
Management
After appropriate cultures are drawn begin empiric antibiotic therapy.
- Consult transplant ID (has been shown to improve mortality and re-hospitalization).
- If patient needs antibiotics, cover broadly for hospital-acquired infections including pseudomonas and MRSA (especially early after transplant).
- Early surgical consult if evidence of devitalized tissue or fluid collections.
Key Points
- Risk of infection differs depending on the time since transplant.
- Clinical signs or symptoms of infection may be subtle.
- Lower threshold for more sensitive imaging such as CT or MRI.
- Consult transplant ID and consider surgical consult if need for debridement or drainage.
Fishman, JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357:2601.
Green M. Introduction: Infections in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:3.
Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases, Sixth Edition. Churchill Livingstone;2005.
Key words: Transplant, CMV, immunocompromised, Candida, Aspergillus, PTLD, BK virus, rejection