Nocardiosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Nocardiosis is an infectious disease affecting either the lungs (pulmonary nocardiosis) or the whole body (systemic nocardiosis). It is due to infection by bacterium of the genus Nocardia, most commonly Nocardia asteroides or Nocardia brasiliensis.

It is most common in men, especially those with a compromised immune system. In patients with brain infection, mortality exceeds 80%; in other forms, mortality is 50%, even with appropriate therapy. It is one of several conditions that have been called the great imitator.^[1]Cutaneous nocardiosis commonly occurs in immunocompetent hosts.^[2]

Diagnosis may be difficult.Nocardiae are weakly acid-fast organisms and can be visualized by modified Ziehl Neelsen stains like Fite-Faraco method. In the clinical laboratory, routine cultures may be held for insufficient time to grow nocardiae, and referral to a reference laboratory may be needed for species identification.

Infiltration and pleural effusion are usually seen via x-ray.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The majority of cases are caused by the Nocardia asteroides complex (at least 50% of invasive infections). The N. asteroides complex is comprised of N. abscessus, N. cyriacigeorgica, N. farcinica, and N. nova. Other known pathogenic species of Nocardia include N. transvalensis complex, N. brasiliensis, and N. pseudobrasiliensis.

Pulmonary, disseminated and CNS infections are acquired through inhalation; primary cutaneous disease is acquired through inoculation of the skin. Rarely, nosocomial postsurgical transmission occurs.

Normally found in soil, these organisms cause occasional sporadic disease in humans and animals throughout the world. The usual mode of transmission is inhalation of organisms suspended in dust. Transmission by direct inoculation through puncture wounds or abrasions is less common. Generally, nocardial infection requires some degree of immune suppression.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

In the United States, it has been estimated that 500-1,000 new cases of Nocardia infection occur annually. Approximately 60% of nocardiosis cases are associated with pre-existing immune compromise. Although incidence data are extremely limited, the number of cases is likely rising as a result of the increase in the number of severely immunocompromised persons.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Severely immunocompromised persons are at greatest risk for nocardiosis. These include persons with connective tissue disorders, malignancy, HIV infection, pulmonary alveolar proteinosis, alcoholism, or high-dose corticosteroid use.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Complications of nocardial infections vary depending on what parts of the body are involved. Certain lung infections may lead to scarring and chronic shortness of breath. Skin infections may lead to scarring or disfigurement. Brain abscesses may lead to loss of neurological function.

Approximately 10% of cases with uncomplicated pneumonia are fatal. The case-fatality rate increases with overwhelming infection, disseminated disease, or brain abscess. Surgical drainage may be indicated and may improve patient outcome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Nocardia is a genus of Gram-positive, catalase-positive, rod-shaped bacteria; some species are pathogenic (nocardiosis).^[1] Nocardia are found worldwide in soil that is rich with organic matter. Most Nocardia infections are acquired by inhalation of the bacteria or through traumatic introduction.

Nocardia colonies have a variable appearance, but most species appear to have aerial hyphae when viewed with a dissecting microscope, particularly when they have been grown on nutritionally-limiting media. Nocardia grow slowly on non-selective culture media, and are strict aerobes with the ability to grow in a wide temperature range. Some species are partially acid fast due to the presence of intermediate-length mycolic acids in their cell wall.

The various species of Nocardia are pathogenic bacteria with low virulence; therefore clinically significant disease most frequently occurs as an opportunistic infection in those with a weak immune system, such as small children, the elderly, and the immunocompromised. Nocardial virulence factors are the enzymes catalase and superoxide dismutase (which inactive reactive oxygen species that would otherwise prove toxic to the bacteria), as well as a “cord factor” (which interferes with phagocytosis by macrophages by preventing the fusion of the phagosome with the lysosome).

Nocardia asteroides is the species of Nocardia most frequently infecting humans, and most cases occur as an opportunistic infection in immunocompromised patents.

The most common form of human nocardial disease is a slowly progressive pneumonia, whose common symptoms include cough, dyspnoea (shortness of breath), and fever. It is not uncommon for this infection to spread to the pleura. Pre-existing pulmonary disease, especially pulmonary alveolar proteinosis, increases the risk of contracting a Nocardia pneumonia.

Nocardia may also cause a variety of cutaneous infections such as actinomycetoma (especially Nocardia brasiliensis), lymphocutaneous disease, cellulitis and subcutaneous abscesses.

About 33% of people with Nocardia infection, this will take the form of encephalitis and/or cerebral abscess formation.

Antibiotic therapy with a sulfonamide is the treatment of choice. The most common sulfonamide used is trimethoprim-sulfamethoxazole. People who take trimethoprim-sulfamethoxazole for other reasons, such as prevention of pneumocystis jiroveci infection in AIDS, have fewer nocardia infections. High-dose imipenem and amikacin have also been used in refractory cases. Antibiotic therapy may have to be continued for six months to a year. Proper wound care is also critical.

Despite that Nocardia has interesting and important features such as production of antibiotics and aromatic compound-degrading or converting enzymes, the genetic study of this organism has been hampered by the lack of genetic tools. However, practical Nocardia–E. coli shuttle vectors have been developed recently.^[2]

• Genome sequence of N. farcinica IFM 10152

• MicrobeWiki’s N. farcinica Page, Current as of June 2007

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