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Infections in the Immunocompromised Host

Alexandra F. Freeman, Jennifer M. Cuellar-Rodriguez

As a result of improvements in antimicrobials and immunosup- clear infection, such as in the gastrointestinal (GI) and genito-
1,2
pressant agents, there are increasing numbers of hosts with urinary tract, but also in response to infection. Therefore
immune deficiencies, either acquired primarily through genetic although necrotic and purulent centers may form in liver and
defects or acquired secondarily, for example, through treatment lymph node infections, the yield with drainage may be poor
for malignancy and autoimmune disease, or after solid or because of the thicker consistency of granulomatous inflamma-
hematopoietic stem cell transplantation (HSCT). Understanding tion. At times, the infected lymph nodes may need resection to
both the genetic defects and the immunological targets of cure infections. Likewise, in lung infections, fine-needle aspiration
immunosuppressant agents will help further the knowledge of frequently provides a higher yield than bronchoscopy because
host control of infection. In this chapter, we review the infection of the nature of inflammation. In addition, it is important to
spectrum of some of the major classes of primary immunode- alert the microbiology laboratory when G. bethesdensis is sus-
ficiencies, as well as acquired immunodeficiency, opportunistic pected, such as with lymphadenitis, as growth requires special
infections in patients with human immunodeficiency virus (HIV) media.
and acquired immunodeficiency syndrome (AIDS) are described The granulomatous inflammation seen in CGD infections
separately in Chapter 39. may be intense enough to impede successful treatment of infection
solely with antimicrobials and necessitate corticosteroid addition
PRIMARY IMMUNODEFICIENCIES to appropriate antimicrobials. For instance, “mulch pneumonitis”
occurs with large inhalations of decaying organic matter, such
Phagocyte Defects (Chapter 22) as mulch. A diffuse pneumonitis associated with Aspergillus
4
Phagocytic neutrophils and monocytes are key members of the results and can be quite fulminant, with a high mortality if the
primary immune response. Neutrophils are essential in the initial inflammatory response is not treated (e.g., with corticosteroids)
host defense against microbes. Antimicrobial peptides, cytokines, in addition to antifungals. There is suggestion that the addition
and chemokines released at the site of microbial entry cause of corticosteroids may help with other infections in CGD, such
neutrophils to migrate to the site of inflammation (chemotaxis), as Nocardia pneumonia and S. aureus liver abscesses. 5,6
ingest, and then kill the microbe through oxygen-dependent or Trimethoprim–sulfamethoxazole (TMP-SMX) is effective
oxygen-independent mechanisms. Defects in quantity or quality against the majority of bacterial pathogens in CGD and thus is
of neutrophils can predispose to infection, which is primarily an ideal prophylactic antibiotic and has been shown to signifi-
7
with fungi and bacteria (Table 37.1). Defects in monocytes are cantly decrease bacterial infections. Itraconazole was shown to
7
less frequent and contribute to control of intracellular bacteria, be effective in preventing some of the fungal infections. The
mycobacteria, and fungi. newer triazoles, including voriconazole and posaconazole, have
not been studied as prophylactic antimicrobials in this setting
Chronic Granulomatous Disease but have an extended spectrum and would likely be effective as
Chronic granulomatous disease (CGD) causes the most common well. Toxicities of extended use with certain antimicrobials need
qualitative neutrophil immunodeficiency. Defects in the nico- to be considered; for instance, voriconazole is associated with
tinamide adenine dinucleotide phosphate (NADPH) oxidase photosensitivity and increased skin cancers with prolonged use,
cause an abnormal neutrophil respiratory burst, leading to as well as fluoride toxicity in rare cases. 8,9
recurrent bacterial and fungal infections. However, it is interesting
that the spectrum of infections is fairly limited, with the most Leukocyte Adhesion Deficiencies
common pathogens being Staphylococcus aureus, Burkholderia Leukocyte adhesion deficiencies (LADs) result from the inability
1-3
2
cepacia, Serratia marcescens, Nocardia spp., and Aspergillus spp. of neutrophils to migrate to the site of infection. LAD-1 is
Other infecting organisms occur less frequently but are rare most frequent, resulting from a defect in β 2 integrin and pre-
outside of CGD, and these include Chromobacterium violaceum, senting typically with failure of umbilical cord separation and
Aspergillus nidulans, and Granulibacter bethesdensis. 3 omphalitis. The spectrum of infection is not as specific as with
Infections in CGD are typically of the lung, lymph nodes, CGD but is limited typically to bacterial infections. Gingivitis
liver, and bone (Fig. 37.1). and periodontitis lead to frequent oral bacterial infections, and
Identification of the infecting organism is essential in CGD necrotizing ulcerative skin infections are common, typically with
to guide antimicrobial therapy. CGD is not only characterized S. aureus or gram-negative bacteria (GNB). Although primarily
by exuberant granulomatous inflammation, both in areas without a defect of neutrophils resulting in bacterial infections, viral

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