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Nocardiosis
Definition
Nocardiosis refers to infections caused by Nocardia spp. Nocardia most commonly causes pneumonia but also can infect the central nervous system (CNS) and the skin. Less commonly, this organism can disseminate throughout the body. These infections usually occur in immunosuppressed patients.
The Pathogen
Nocardia spp are thin, aerobic, gram-positive bacilli that form branching filaments. The bacteria stain irregularly and appear beaded on Gram stain and positive on modified acid-fast stain. The species are now identified by gene sequencing and DNA-DNA hybridization. The number of species causing human disease is large and includes N. abscessus, N. brevicatena/paucivorans complex, N. nova complex, N. transvalensis complex, N. farcinica, N. cyriacigeorgica, N. otitidiscaviarum, N. veterana , N. brasiliensis , and N. pseudobrasiliensis .
Epidemiology
Nocardia spp are ubiquitous and primarily originate in soil. Despite being found throughout the environment, they rarely cause symptomatic infection in humans. Because nocardiosis is not a reportable disease, the frequency of this disease is unknown. The annual incidence has been estimated to be 0.4 to 0.5 in 100,000. The risk for symptomatic Nocardia infection is greatly increased (estimated to be 140 to 340 times greater) in individuals who are immunocompromised, including patients who are receiving immunosuppressive agents following a stem cell or solid organ transplant, and patients with acquired immunodeficiency syndrome (AIDS). Corticosteroids are the most frequent immunosuppressant associated with nocardiosis, but cases also have been reported in patients who are receiving anti–tumor necrosis factor-α antibody agents as well as other immunosuppressants. Trimethoprim-sulfamethoxazole prophylaxis, as is used to prevent infections with Pneumocystis jiroveci , does not always protect against Nocardia . Other at-risk groups include patients with cancer, Cushing syndrome ( Chapter 208 ), chronic granulomatous disease ( Chapter 231 ), and hypogammaglobulinemia ( Chapter 231 ). Patients with chronic pulmonary disorders, particularly alveolar proteinosis ( Chapter 79 ), are also more susceptible to this infection. In approximately one third of patients with nocardiosis, no predisposing condition can be identified.
Pathobiology
Most Nocardia spp gain entry to the host via the respiratory tract or, less commonly, by skin inoculation. Invading bacteria elicit a neutrophilic response that inhibits but does not kill the organism. The bacteria are phagocytosed by neutrophils and macrophages and then become enclosed in a membrane-bound phagolysosome. In this closed environment, neutrophils and macrophages can kill many species of bacteria by synthesizing superoxide and hydrogen peroxide. However, Nocardia can survive by producing superoxide dismutase, an enzyme that inactivates these toxic oxygen byproducts. In addition, Nocardia spp produce a mycolic acid called cord factor that inhibits the fusion of lysosomes with the phagolysomal compartment, thereby preventing toxic proteases and other antibacterial products from reaching the intracellular bacteria. Cell wall extractable lipids impair phagocytosis and inhibit bacterial killing. In addition to neutrophils and macrophages, cell-mediated and humoral immunity also play roles in protecting the host against Nocardia invasion, thereby explaining the wide range of immunocompromised patients that are at increased risk for contracting nocardiosis.
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