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C H A P T E R 89

CLINICAL APPROACH TO INFECTIONS IN

THE COMPROMISED HOST

Samuel A. Shelburne, Russell E. Lewis, and Dimitrios P. Kontoyiannis

Advances in the supportive care and treatment of hematologic may persist for more than 1 year after intensive radiation therapy or
malignancies have markedly improved the life expectancy of afflicted after HSCT.
patients, but this progress is increasingly at the expense of developing
a wider range of infectious complications often caused by drug-
resistant organisms. The clinical approach to infections occurring Acute Leukemias
among hematology patients involves understanding host immune
system defects and anatomic barrier disruption that predispose In patients with acute leukemias, a major cause of morbidity is
patients to infection (Fig. 89.1). This chapter reviews specific hema- infection due to drug-associated mucositis and therapy-induced
tologic conditions for their unique host defense defects and associated neutropenia. Most infections occurring during neutropenia are bacte-
infections (Table 89.1) and the differential diagnoses of common rial, but patients with prolonged neutropenia are at additional risk
infectious pathogens (Table 89.2). To demonstrate how periods of for development of yeast and mold infections. Patients with acute
predictable anatomic defects combine with severe immune compro- leukemia who progress to advanced therapies, such as hematopoietic
mise, the prevention, diagnosis, and management strategies for cell transplant, have added risk for infections associated with acquired
infections occurring in the hematopoietic stem cell transplant deficiencies in cell-mediated and humoral immunity, such as Pneu-
(HSCT) recipient are presented as models. 1 mocystis jirovecii and CMV infections. 1

HEMATOLOGIC CONDITIONS PREDISPOSING Chronic Leukemias
TO INFECTION Patients with chronic myeloid leukemia do not have prominent host
Malignant Hematologic Disorders defense impairments, so infections are limited unless patients proceed
to aggressive chemotherapy or HSCT. Host defense defects with
tyrosine kinase inhibitors, such as imatinib or dasatinib, have not
Antineoplastic Therapy been well defined. Chemotherapy for blast crisis resembles therapy
for acute leukemia. Patients with CLL are predisposed to infection
During antineoplastic treatment, cytotoxic agents frequently are because of immunodeficiency related to the leukemia itself (humoral
administered in combination with other immunosuppressive thera- and cellular immune dysfunction) and to therapy-related immuno-
4
pies, such as corticosteroids or radiation therapy. Several cytotoxic suppression. In early B-cell CLL, the infectious risk is mainly related
agents, notably methotrexate, cyclophosphamide, 6-mercaptopurine, to unbalanced immunoglobulin chain synthesis and resultant hypo-
and azathioprine, impair cell-mediated immunity. Many of the drugs gammaglobulinemia. In patients with advanced CLL, particularly
themselves (e.g., cyclophosphamide) also impair humoral responses after the introduction of therapy with purine analogues and mono-
and produce quantitative phagocyte defects. Fludarabine, a major clonal agents (e.g., rituximab, alemtuzumab), neutropenia and defects
therapy for chronic lymphocytic leukemia (CLL), can produce pro- in cell-mediated immunity are other factors predisposing to infection.
longed and profound defects in cell-mediated immunity, thereby The risk for infectious complications increases with the duration of
increasing susceptibility to Pneumocystis, yeast, and herpes group CLL, reflecting the cumulative immunosuppression related to its
viruses (herpes simplex virus [HSV], varicella-zoster virus [VZV], treatment. The incidence of infection correlates with the serum
and cytomegalovirus [CMV]). levels of immunoglobulins (particularly IgG), which may be further
The use of monoclonal antibody therapy for hematologic disorders impaired by use of anti-CD20 therapies.
2
results in dysfunction of particular aspects of the immune system.
Rituximab results in a sustained depletion of B lymphocytes for 6 to
9 months and has been specifically associated with reactivation of Lymphomas
3
hepatitis B virus infection. Alemtuzumab administration causes
profound lymphopenia and an increased risk for a variety of viral and Hodgkin and non-Hodgkin lymphoma are commonly associated with
fungal infections. impaired cell-mediated immunity. The degree of immune impairment
Exogenous administration of glucocorticoids leads to increased may correlate with the extent of disease and often is compounded by
3
susceptibility to infection. The degree of immunosuppression and the administration of immunosuppressive therapy. The intrinsic impair-
relative risk for infection depend on the dose and duration of use. ment of cell-mediated immunity in Hodgkin lymphoma can persist
The major effect of steroids on granulocyte function is a decrease in even after apparent cure. Splenectomy-related infections occur with
chemotactic activity. This accounts, in part, for the clinical observa- sepsis caused by encapsulated bacterial organisms at a median of 22
tion that the signs and symptoms of severe infections may be masked months but sometimes many years after surgery.
or greatly reduced in patients receiving steroids. Steroids may enhance
susceptibility to infection by means of negative effects on glucose
homeostasis, wound healing, skin fragility, monocyte and lymphocyte Myelodysplastic Syndrome
function, production of cytokines, and humoral immune responses.
Radiation therapy has been associated with granulocyte dysfunc- Neutrophils and band forms from patients with myelodysplastic
tion and delayed wound healing. Defects in cell-mediated immunity syndrome are functionally defective and probably are derived from a

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