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A key element in the effective care of immunocompromised patients with fever is hypervigilance. Not only are these patients at increased risk for a diverse range of microorganisms, but also infections caused by these organisms can present in subtle or atypical ways and often progress to difficult-to-treat chronic disease states or rapid clinical decompensation. Therefore, empiric anti-infective therapy is justified for new-onset fever in immunocompromised patients while a thorough investigation into the source of fever is performed. Because antimicrobial therapies often have adverse side effects, an accurate evaluation to guide definitive antimicrobial therapy becomes crucial.

General features of a thoughtful diagnostic approach to fever in immunocompetent patients remain valid for immunocompromised patients, including consideration for noninfectious diagnoses (see Chapter 223). Likewise, exposure history remains essential and must be expanded to include microorganisms traditionally considered to be “environmental” or of “low virulence.” Published guidelines for the use of antimicrobial agents in immunocompromised children outline contemporary standards of care and can provide useful algorithms to help improve patient outcomes. One key principle is the importance of frequent reevaluations of immunocompromised patients’ course and care. Furthermore, optimal care may require input from an infectious diseases physician with expertise in treating immunocompromised patients infected with microorganisms that are often difficult to diagnose or treat like fungi or mycobacteria.


In developed countries, immunodeficiency is commonly acquired. Severe connective tissue disease, hematopoietic cell transplantation (HCT), and solid organ transplantation (SOT) inherently cause immune suppression, which is often worsened by immuno­suppressive drugs used to prevent deleterious auto- and allo-immunity. In developing countries, acquired conditions such as human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and severe malnutrition cause significant immunodeficiency.

Patients with primary immunodeficiency often cannot eradicate infection until immune function is restored through allogeneic HCT, enzyme replacement therapy (for patients with adenosine deaminase deficiency), or gene therapy. Similarly, immune function in patients with acquired immunodeficiencies like HIV or immunosuppressive therapy can sometimes be clinically improved via immunomodulatory therapies that suppress viral load (eg, antiretroviral therapy [ART]) or stimulate neutrophil production (eg, granulocyte colony-stimulating factor [GCSF]), which work in combination with antimicrobial therapy to eradicate infection.

Defects in immunologic functions (see Chapters 183 and 184) correlate with increased patient risk for infection (Table 224-1). For example, T-cell–mediated immunity is particularly important for defense against fungal and viral infections. The reticuloendothelial function of the spleen is necessary to clear encapsulated bacteria from the blood, and terminal complement components lyse opsonized bacteria such as Neisseria meningitidis. Neutrophil oxidative bursts kill catalase-positive bacteria and fungi within neutrophils, and antitoxin antibodies prevent toxic shock induced by the toxic shock syndrome toxin (TSST)-1 superantigen as well as directly kill bacterial pathogens. Therefore, immune defect–specific risks offer basic insights into the diagnostic workup and the use of prophylactic and empiric antimicrobials for immunocompromised children. Conversely, certain infectious disease presentations provide ...

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