Infections in the immunocompromised patient

Commonly encountered immunocompromising conditions

Immunocompromise can be broadly defined as a state in which the response of the host to a foreign antigen is subnormal. It can be congenital (primary) or acquired. Congenital immunodeficiencies are now much less common than acquired immunodeficiencies. In general, congenital immunodeficiency is observed more frequently in patients in pediatric ICUs than in those in adult ICUs. Patients with congenital immunodeficiencies usually have repeated infections, especially infections affecting the sinuses and lower respiratory tract. Congenital immunodeficiencies are usually “pure,” in that the defects in the host response to foreign antigens are usually specific and well defined. For example, Bruton X-linked agammaglobulinemia is associated with a defect in the normal maturation process of immunoglobulin-producing B cells. As a result, mature circulating B cells, plasma cells, and serum immunoglobulin are absent. The patient is susceptible to organisms, such as Streptococcus pneumoniae and Haemophilus influenzae, normally dealt with by immunoglobulins. Other congenital immunodeficiency syndromes are listed in Table 121.1 .

Most immunocompromised patients managed in adult ICUs have acquired immunocompromise. Although the response of host defenses in the elderly, people with diabetes, and people with alcohol use disorder is compromised, this chapter deals primarily with four categories of immunocompromised patients: (1) patients receiving therapy for hematologic malignancies and solid tumors; (2) patients receiving immunosuppressive therapy in the context of solid organ transplantation; (3) patients receiving corticosteroids, methotrexate, monoclonal antibodies to tumor necrosis factor, and other disease-modifying agents for rheumatoid arthritis, Crohn disease, and autoimmune disorders; and (4) patients with human immunodeficiency virus (HIV) infection.

General diagnostic approach to immunocompromised patients with severe infections

Immunocompromised patients are a heterogeneous group. The infections commonly encountered by a patient with neutropenia as a consequence of chemotherapy may be different from infections observed in a patient with rheumatoid arthritis who is receiving infliximab. Even within a particular category, different renal transplantation recipients, for example, may have a different degree of immunocompromise and a different susceptibility to infection. In solid organ transplant recipients, the “net state of immunosuppression” (i.e., the cumulative burden of immunosuppression with a special weighting toward recent T-cell ablative therapy) influences the risk of infection. A renal transplant recipient who is receiving tacrolimus monotherapy twice per week would be less susceptible to opportunistic infection than a patient with recent acute cellular rejection who is receiving OKT3 or alemtuzumab. There have been attempts to quantify immune function in solid organ transplant recipients, although it has not yet been definitively proved that such tests predict infection risk. In contrast, with HIV infection, CD4 lymphocyte count and HIV RNA quantification (“viral load”) predict risk of infection. Patients with CD4 counts greater than 500 cells/mm ³ are unlikely to be infected with an opportunistic pathogen, whereas those with CD4 counts of 200–500 cells/mm ³ may be infected with organisms such as Mycobacterium tuberculosis, but they are unlikely to be infected with opportunistic pathogens such as CMV or Mycobacterium avium complex. Patients with CD4 counts less than 200 cells/mm ³ have an increased risk of a wide variety of opportunistic infections.

Specific environmental exposures may be potentially important for immunocompromised patients. A travel history to the deserts of the southwestern United States and northern Mexico, for example, may increase the likelihood that an immunocompromised patient has coccidioidomycosis ; histoplasmosis is endemic in the Ohio River Valley. Alternatively, there may be environmental risks within the ICU. Outbreaks of invasive pulmonary aspergillosis have been linked to construction activity within the hospital. Outbreaks of legionellosis may be waterborne via air conditioning cooling units, drinking water, or aerosolization from showers. Furthermore, it is possible that many fungal and bacterial infections are waterborne. ^, Tuberculosis transmission has been well described in ICUs caring for transplant recipients or HIV-infected patients. In summary, the net state of immunosuppression must be considered in the context of recent environmental exposures.

Although elements of history taking and physical examination may narrow the differential diagnosis of the causative agent of infection in immunocompromised patients, some of the “rules” applied to diagnosis in immunocompetent patients do not apply. Caution must be exercised in use of the diagnostic principle that follows Occam’s razor: “entities are not to be multiplied without necessity.” In an immunocompetent patient, given all the patient’s symptoms, signs, and noninvasive laboratory test results, one unifying diagnosis usually explains all. Importantly, in contrast, immunocompromised patients may have more than one infection at any given time. A neutropenic patient may have bacterial pneumonia and invasive pulmonary aspergillosis simultaneously, whereas an immunocompromised patient with HIV infection may have P. jirovecii pneumonia and pulmonary infiltrates because of human herpesvirus (HHV)-8 infection (Kaposi sarcoma).

The potential for multiple diagnoses underscores the need for early invasive testing in immunocompromised patients with severe infection. Patients with unexplained severe community-acquired pneumonia may be best managed by early bronchoalveolar lavage performed before antimicrobial therapy has commenced. Bronchoalveolar lavage could be sent for Gram stain, Ziehl-Neelsen stain, modified acid-fast stain, calcofluor stain, direct fluorescent antibody tests, polymerase chain reaction (PCR), and cytologic analysis to enable rapid diagnosis of infection with bacteria, mycobacteria, Nocardia , fungi, Legionella, CMV, community-acquired respiratory viruses, and P. jirovecii . Close liaison with the microbiologic laboratory is vital to ensure that appropriate attempts are made to identify the causative pathogens as rapidly as possible. For example, newer microbiologic techniques such as mass spectrometry, matrix-assisted laser desorption/ionization (MALDI-TOF) and DNA sequencing have been demonstrated to be useful in identifying fungal isolates rapidly. The bronchoalveolar lavage should be inoculated onto solid media, and molecular diagnostic testing should be used as appropriate. An outline of the diagnostic approach in immunocompromised patients is given in Box 121.1 .