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Key Features

Essentials of Diagnosis

  • Fever and other symptoms may be blunted because of immunosuppression

  • Organisms considered "nonpathogenic" may cause serious illness

  • The interval since transplantation and the degree of immunosuppression can narrow the differential diagnosis

  • Early empiric broad-spectrum antimicrobial therapy is often indicated because of the high infection-related morbidity and mortality

General Considerations


  • Risk factors

    • Plasma cell myeloma

    • Chronic lymphocytic leukemia (and small lymphocyte lymphoma)

    • Acquired and congenital hypogammaglobulinemia

    • Asplenia

  • Increased infections with encapsulated organisms such as Haemophilus influenzae and Streptococcus pneumoniae

  • Although normally thought of as being linked to impaired cellular immunity, there is an association between rituximab (anti-B cell monoclonal antibody) therapy and development of

    • Pneumocystis jirovecii infection

    • Progressive multifocal leukoencephalopathy (PML)

    • Hepatitis B reactivation


  • Risk factor is absolute granulocyte count below 1000/mcL (1.0 × 109/L), and especially below 100/mcL (0.1 × 109/L)

  • Increased infections with:

    • Gram-negative enteric organisms (particularly Pseudomonas)

    • Gram-positive cocci (particularly Staphylococcus aureus, Staphylococcus epidermidis, and viridans streptococci)

    • Candida

    • Aspergillus

    • Other fungi such as Trichosporon, Scedosporium, Fusarium, and the mucormycoses


  • HIV infection, lymphoreticular malignancies such as Hodgkin disease, immunosuppressive medications

  • Increased infections by a large number of

    • Bacteria, such as Listeria, Legionella, Salmonella, and Mycobacteria

    • Viruses, such as herpes simplex, varicella, and cytomegalovirus (CMV)

    • Fungi, such as Cryptococcus, Coccidioides, Histoplasma, and Pneumocystis

    • Protozoa, such as Toxoplasma


  • Infections that occur immediately after the transplant often involve the transplanted organ

    • Lung: pneumonia and mediastinitis

    • Liver: intra-abdominal abscess, cholangitis, and peritonitis

    • Kidney: urinary tract infections, perinephric abscesses, and infected lymphoceles

  • In contrast to solid organ transplants, in stem cell transplants the source of fever cannot be found in 60–70% of patients

  • Most infections that occur in the first 2–4 weeks after transplant are related to

    • The operative procedure and to the hospitalization itself (wound infection, intravenous catheter infection, indwelling urinary catheter–related urinary tract infection)

    • The transplanted organ

    • Compensated transplantations performed abroad through "medical tourism"; can introduce additional risk for infections, which vary by country and by transplant setting

  • Infections that occur between the first and sixth months after transplant are often related to immunosuppression

    • Reactivated herpes simplex, varicella-zoster, and CMV infections are quite common

    • Opportunistic infections with fungi (Candida, Aspergillus, Cryptococcus, Pneumocystis, and others), Listeria monocytogenes, Nocardia, and Toxoplasma are also common

  • After 6 months, when immunosuppression has been reduced to maintenance levels, infections that are found in any population occur


  • Patients taking TNF inhibitors (infliximab, etanercept, adalimumab, certolizumab pegol, golimumab) have ...

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