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A key element in the effective care of immunocompromised patients with fever and infection is hypervigilance. Not only are these patients at increased risk from a diverse range of microorganisms, but also their resulting infections can present with subtle or atypical symptoms and can progress to difficult-to-treat chronic disease states, or to acute life-threatening clinical decompensations. Given these facts, empiric anti-infective therapy is sometimes justified before the definitive cause of a fever is elucidated. Yet, the same facts also argue for the vital importance of making an accurate and exact diagnosis, to guide definitive ongoing therapy.

Toward this end, the general features of a thoughtful diagnostic approach to fevers in immunocompetent patients remains valid for immunocompromised patients, including a systematic consideration of noninfectious diagnoses (see Chapter 228). Likewise, a thorough exposure history remains essential and is expanded to include microorganisms traditionally considered to be “environmental” or of “low virulence.”

Published guidelines for the use of antimicrobial agents in certain sets of immunocompromised patients outline contemporary standards of care and can provide useful algorithms to help improve outcomes for these patients (for clinical practice guidelines, refer to However, a key first principle of such guidelines should be the importance of frequent reevaluation of an immunocompromised patient’s course and care, given his or her extreme medical vulnerability. Furthermore, optimal care may require input from a physician with expertise in treating immunocompromised patients infected with microorganisms that are often difficult to treat, such as fungi or mycobacteria.

Defined defects in particular immunologic functions (see Chapters 187 and 188) correspond with increased patient risk for specific infections (Table 229-1). These immune defect–specific risks offer basic principles and insights to influence diagnostic workup and empiric therapy for children known to have a particular type of immunocompromise. Conversely, certain infectious disease presentations provide clues to trigger and guide an evaluation to first diagnose specific immune defects in children.

Table 229-1. Immunologic Functional Defects and Susceptibility to Infections

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