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Overview

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A growing group of individuals who have acquired immunodeficiency syndrome (AIDS), who are receiving immunosuppression for solid-organ transplantation, bone marrow transplantation (BMT), or for autoimmune (“connective tissue” diseases), who have primary immune deficiencies, or who have been treated with chemotherapeutic regimens for cancer, have increased susceptibility to infection as a result of acquired or intrinsic immune deficiencies. Prolonged survival of such immunocompromised individuals reflects the deployment of newer laboratory assays and newer antimicrobial agents, including antifungal, antibacterial, and antiviral agents (e.g., ganciclovir, foscarnet, oral agents) and highly active antiretroviral therapies (HAART) for HIV infection, hematopoietic growth factors, and clinical experience in caring for such patients. Wide use of immunosuppressive drugs, including “biologic agents,” which are generally antibodies targeting specific cell types or pathways of inflammation, has further expanded susceptible populations.

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Major challenges in providing care to these patients include systemic infections for which therapies or vaccines are limited or absent (e.g., management of respiratory viruses) and progressive antimicrobial resistance of common pulmonary pathogens, including Staphylococcus aureus, Enterococcus, Pseudomonas, Acinetobacter, Stenotrophomonas (formerly Xanthomonas), and Burkholderia species. In addition, selection of novel strains of bacteria, including nontuberculous mycobacteria and Nocardia species, has proved challenging. Resistance has increased to antimicrobial agents commonly used for prophylaxis (i.e., TMP-SMX and fluoroquinolones).

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An essential difference exists in the management of pneumonia in immunocompromised individuals when compared with normal hosts. Given the broad spectrum of potential pathogens and of noninfectious processes that may mimic infection, coupled with the inherent toxicities of many therapies, a specific microbiologic diagnosis should be considered essential to the management of pulmonary processes in the immunocompromised host.

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General Principles of Management of Opportunistic Infection

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Important principles underlying the management of opportunistic infections in immunocompromised patients are discussed below.

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Opportunistic infection is defined as infection occurring as a result of compromised immune function and that would not be expected to occur, or would otherwise cause disease of lesser intensity in the presence of normal immune function. Thus, immunocompromised individuals are subject to infections commonly present in the community; however, these infections are likely to be of greater frequency or severity than in the immunologically normal host. In addition, infection in these patients may be caused by organisms of low native virulence or that cause insignificant disease in the normal host, including such organisms as Pneumocystis jiroveci (PCP) or cytomegalovirus (CMV).

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The risk of infection in any patient is determined by the interaction of two factors: the potential pathogens to which the individual is exposed (epidemiologic exposures), and a measure of the individual's susceptibility to infection, termed the “net state of immunosuppression” (Table 123-1).13 The occurrence of infection in an individual at a time when the immune status of the patient is thought to be nearly normal is evidence that either an excessive environmental exposure has ...

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