Etiology

Nocardia is a member of the order Actinomycetales, which includes gram-positive filamentous bacteria such as Actinomyces, Streptomyces, and mycobacteria. Nocardia organisms are environmental saprophytes that are ubiquitous in soil and decaying vegetable matter. These organisms are obligate aerobes and grow on ordinary culture media. Growth is achieved best at 37°C, although many isolates of Nocardia are thermophilic and grow at temperatures up to 50°C. At 25°C, the organisms grow very slowly. Colonies appear within 1-2 wk on brain-heart infusion agar and Lowenstein-Jensen media, usually as waxy, folded, or heaped colonies at the edges. With further incubation, the colonies develop aerial hyphae that tend to give them a white, chalky appearance. With modified Kinyoun acid-fast staining of biopsy specimens or body fluids, Nocardia demonstrates fragmented bacilli with stain concentrated in a beaded pattern along portions of the branching filaments.

Numerous taxonomic studies have established the heterogeneity of Nocardia asteroides, the most common species causing human nocardiosis. N. asteroides is identified from its colony and microscopic morphology, resistance to lysozyme, and inability to hydrolyze casein, tyrosine, xanthine, and hypoxanthine. N. asteroides, Nocardia farcinica, Nocardia otitidis-caviarum, Nocardia transvalensis, and Nocardia nova complex have similar features, a fact that has contributed to the apparent heterogeneity of Nocardia. Molecular techniques utilizing 16S recombinant RNA gene sequencing with a database search for matches have led to new Nocardia species identification in human disease (e.g., Nocardia beijingensis). N. brasiliensis is the 2nd most common etiologic agent of human nocardiosis. Some strains of N. brasiliensis have been assigned to a new species, Nocardia pseudobrasiliensis. Antibiotic susceptibility testing, biochemical testing, and newer molecular typing techniques such as gene sequencing have currently identified at least 16 species within the genus Nocardia.

N. asteroides complex includes the most common agents of systemic nocardiosis in the USA. N. brasiliensis is the principal cause of localized nocardial cellulitis and lymphadenitis in immunocompetent children and can also cause pulmonary and systemic disease, especially in immunocompromised persons. N. brasiliensis is found more commonly in the southern USA, Central America, South America, and Asia. Actinomadura madurae (Madura foot), Nocardia farcinica, Nocardia nova, and Nocardia transvalensis also cause human disease.

Epidemiology

Once thought to be a rare cause of human disease, nocardiosis is being recognized more frequently, and has been diagnosed in persons from 4 wk to 82 yr of age. Almost all patients have compromised cellular immunity from an underlying disease such as organ transplantation, malignancy, corticosteroids, diabetes, HIV infection, or primary immunodeficiency, especially chronic granulomatous disease (Chapter 124). Nocardia infections among stem cell transplant recipients are associated with a high rate of concomitant invasive fungal infection and a notable lack of protection with trimethoprim-sulfamethoxazole prophylaxis. An evaluation of opportunistic infections in 547 organ transplant recipients receiving Alemtuzumab (humanized monoclonal CD52 antibody) revealed that 62 opportunistic infections developed in 56 patients (10%), Nocardia being found in 4 patients.

Pathogenesis

Soil is the natural habitat of Nocardia,