Hematologic Malignancies and Solid Tumors

Prolonged neutropenia from chemotherapy has a significant risk of bacterial and fungal infection. Classically, gram-negative organisms such as Pseudomonas aeruginosa and fungal organisms such as Aspergillus species have been associated with severe neutropenia. It has long been known that the severity and duration of neutropenia influence the risk of infection.³ It also has been well established that aggressive chemotherapy and radiotherapy for Hodgkin’s disease coupled with splenectomy significantly impairs humoral defense against encapsulated organisms such as S. pneumoniae, H. influenzae, and Neisseria meningitidis.⁴ Transplantation is associated with a risk of graft-versus-host disease (GVHD). Prophylaxis and treatment for GVHD may involve use of drugs such as cyclosporine or tacrolimus plus corticosteroids. Cyclosporine and tacrolimus inhibit calcineurin, an enzyme important in the lymphocyte activation cascade. Corticosteroids also affect lymphocyte function and depress functions of activated macrophages. As a result, patients receiving therapy for GVHD may be prone to fungal, viral, and mycobacterial infections.

Solid-Organ Transplantation

Solid-organ transplant recipients are uniquely susceptible to infection.⁵ They undergo significant surgery, breaching the defenses provided by the skin. They remain in ICUs for prolonged periods, requiring intravenous access and mechanical ventilation—here, cutaneous and pulmonary barriers to infection are breached. Finally, solid-organ transplant recipients receive immunosuppressive therapy to prevent graft rejection. Commonly used immunosuppressive medications are listed in Table 137-2. Immunosuppressive regimens are in a constant state of flux—more recent trends have been toward aggressive “pretreatment” immediately before transplantation, coupled with decreased immunosuppression in the posttransplant period.⁶

TABLE 137-2 Immunosuppressive Drugs Used in Solid-Organ Transplantation and Their Mechanisms of Activity

In the early posttransplant period, transplant recipients are susceptible to nosocomially acquired bacterial infections such as pneumonia, catheter-related bloodstream infection associated with general ICU care, and wound and intraabdominal infections associated with surgical procedures. Opportunistic infections may be acquired from the organ graft; cytomegalovirus (CMV) is the most pertinent example,⁷ but a wide variety of infections (e.g., rabies, histoplasmosis, tuberculosis, West Nile virus) have been acquired from grafts. Solid-organ transplant recipients, by virtue of their iatrogenic immunosuppression, also are susceptible to reactivation of latent infection (e.g., CMV infection, tuberculosis, histoplasmosis) or to infections acquired through the hospital environment (e.g., aspergillosis, legionellosis, tuberculosis).

Rheumatoid Arthritis and Autoimmune Disorders

Therapy for rheumatoid arthritis and other autoimmune disorders may be with simple analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). Drugs with the potential to cause significant immunocompromise are also frequently used. Classically, therapy has been with corticosteroids or disease-modifying antirheumatic drugs such as azathioprine, cyclosporine, penicillamine, gold salts, hydroxychloroquine, leflunomide, methotrexate, or sulfasalazine. The effects of corticosteroids, azathioprine, and cyclosporine on host defenses have been noted previously (see Table 137-2). Methotrexate reversibly inhibits dihydrofolate reductase and interferes with DNA synthesis, repair, and cellular replication. In addition to its use in rheumatoid arthritis, it also can be used as an antineoplastic agent. Methotrexate can cause significant neutropenia. Low-dose methotrexate is generally less likely to increase infection risk in patients with rheumatoid arthritis.^8,9

A variety of anticytokine agents have become available for rheumatoid arthritis (Table 137-3). Use of these drugs also has been reported in treatment of Behçet’s disease, Crohn’s disease, GVHD, hairy cell leukemia, psoriasis, pyoderma gangrenosum, sarcoidosis, and ulcerative colitis. Considerable attention has been paid to the possibility of tuberculosis developing after treatment with such agents.¹⁰ The risk is sufficiently high that it is recommended that tuberculin skin testing or interferon gamma (IFN-γ) release assays be performed to detect latent tuberculosis before the initiation of anticytokine agents. Invasive infections with Histoplasma, Candida, Pneumocystis jirovecii, Aspergillus, Cryptococcus, Nocardia, Salmonella, Listeria, Brucella, Bartonella, nontuberculous mycobacteria, Leishmania, and Toxoplasma have also been reported associated with the use of these medications.^11–14 As is the case with transplant-associated immunocompromise, these infections may be reactivation of latent infection or new acquisition of organisms through environmental exposure.

TABLE 137-3 Commonly Used Anticytokines for Management of Rheumatoid Arthritis

Human Immunodeficiency Virus Infection

HIV infection remains a relatively common infection, but acquired immunodeficiency syndrome (AIDS) has become less frequently encountered in ICUs since the advent of highly active antiretroviral therapy. A decline in CD4 counts creates a predisposition to P. jirovecii pneumonia, mycobacterial infection, fungal infection (e.g., cryptococcal meningitis), and viral infection (e.g., CMV infection). Many patients with HIV infection are co-infected with hepatitis C virus, and as a result, liver failure is now a relatively common reason for ICU admission in HIV-infected patients. In some centers, liver transplantation is performed in HIV-infected patients with hepatitis virus–induced liver diseases.^15,16

Pulmonary Infection

Pneumonia is a significant cause of morbidity and mortality in immunocompromised patients. In contrast to the normal host, the impaired responsiveness of the immune system means that the disease presents in unusual ways, which may lead to challenges in establishing a diagnosis.

Infectious microorganisms usually gain access to the respiratory tract through inhalation, although hematogenous spread sometimes may occur. Mechanical defenses remove the bulk of potentially harmful agents from the lungs (Table 137-4). Inhaled particles greater than 10 µm in diameter usually become trapped in the upper airways or are removed by coughing or mucociliary clearance. Most bacteria range from 0.5 to 2 µm in size and are able to reach the terminal airways/alveoli and potentially cause infection. In the alveoli, the alveolar macrophages are the first line of defense. Subsequently an inflammatory response consisting of polymorphonuclear neutrophils is important. Finally, specific T-cell and B-cell immune responses are essential for successful defense against many pathogens.

TABLE 137-4 Host Defenses Against Respiratory Infections and How They Are Affected in Immunocompromised Patients

As noted earlier, although it may be possible to pinpoint a major immunologic deficiency, most immunocompromised individuals have an assortment of deficiencies in host defense working together. An organ transplant recipient may be intubated, have multiple intravenous lines, be diabetic, and be on corticosteroids and tacrolimus. All these factors contribute to the overall degree of immunity, each paving the way for its peculiar array of susceptibilities to pulmonary infection. In solid-organ transplant recipients, specific causes of pulmonary infection are most frequent at certain times post transplantation (Table 137-5). In a similar manner, specific causes of pulmonary infection are more frequent at different CD4 lymphocyte counts for patients with HIV infection (Table 137-6).

TABLE 137-5 Occurrence of Pulmonary Infection After Solid-Organ Transplantation Stratified by Time from Transplantation

Time After Transplant (mo)

Organism

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Nosocomial bacteria (e.g., MRSA, ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii) < div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: Low Systemic Arterial Blood Pressure Very High Systemic Arterial Blood Pressure Diarrhea Acute Respiratory Failure Advanced Bedside Neuromonitoring Glomerulonephritis and Interstitial Nephritis Stay updated, free articles. Join our Telegram channel Join Tags: SPEC - Textbook of Critical Care 12 Month Subscription Jul 7, 2016 | Posted by admin in CRITICAL CARE | Comments Off on Infections in the Immunocompromised Patient Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access