Infection in the Immunocompromised Patient

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

IMPAIRED HUMORAL IMMUNITY

• 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

GRANULOCYTOPENIA

• 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

IMPAIRED CELLULAR IMMUNITY

• 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

TRANSPLANTATION

• 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

BIOLOGIC THERAPIES

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