Microbiology

Nocardiae are branching, beaded, gram-positive filaments that usually give positive results with modified acid-fast stains. These saprophytic aerobic actinomycetes are common in soil.

• Nine species or species complexes are most commonly associated with human disease.
• Speciation of nocardiae is precluded in most clinical laboratories, although improvements in mass spectrometry-based techniques may change this limitation in high-resource countries.
• Nocardia brasiliensis is most often associated with localized skin lesions.

Epidemiology

Nocardiosis occurs worldwide and has an incidence of ∼0.375 cases per 100,000 persons in Western countries. The risk of disease is greater than usual among persons who have deficient cell-mediated immunity-e.g., that associated with lymphoma, transplantation, glucocorticoid therapy, HIV infection with <250 CD4+ T cells/µL, or immunomodulating drugs such as tumor necrosis factor inhibitors.

Pathogenesis

Pneumonia and disseminated disease follow inhalation of fragmented bacterial mycelia.

• Nocardiosis causes abscesses with neutrophilic infiltration and necrosis.
• Organisms have multiple mechanisms for surviving within phagocytes.

Clinical Manifestations

• Respiratory tract disease: Pneumonia is usually subacute, presenting over days to weeks, but can be acute in immunocompromised pts.
  • A prominent cough productive of small amounts of thick purulent sputum, fever, anorexia, weight loss, and malaise are common; dyspnea, hemoptysis, and pleuritic chest pain are less common.
  • CXR may demonstrate single or multiple nodular infiltrates of varying sizes that tend to cavitate. Empyema is noted in one-quarter of cases.
  • Extrapulmonary disease is documented in >50% of cases.
• Extrapulmonary disease: In 20% of cases of disseminated disease, lung disease is absent.
  • Nocardial dissemination manifests as subacute abscesses in the brain (most commonly), skin, kidney, bone, eye, and/or muscle.
  • Brain abscesses are usually supratentorial, are often multiloculated, can be single or multiple, and tend to burrow into ventricles or extend into the subarachnoid space.
  • Meningitis is uncommon, and nocardiae are difficult to recover from CSF.
• Disease following transcutaneous inoculation: usually presents as cellulitis, lymphocutaneous disease, or actinomycetoma
  • Cellulitis presents 1-3 weeks after a break in the skin (often with contamination by soil).
    • The firm, tender, erythematous, warm, and nonfluctuant lesions may involve underlying structures, but dissemination is rare.
    • N. brasiliensis and species in the N. otitidiscaviarum complex are most common in cellulitis.
  • Lymphocutaneous disease resembles sporotrichosis and presents as a pyodermatous nodule at the inoculation site, with central ulceration and purulent or honey-colored discharge.
    • SC nodules often appear along lymphatics that drain the primary lesion.
  • Actinomycetoma progresses from a nodular swelling at the site of local trauma (typically on the feet or hands, although other sites can be affected) to fistula formation; dissemination is rare.
    • The discharge is serous or purulent and can contain granules consisting of masses of mycelia.
    • Lesions, which spread slowly along fascial planes to involve adjacent skin and SC tissue and bone, can cause extensive deformity after months or years.
• Eye disease: Endophthalmitis can occur after eye surgery or during disseminated disease.

Diagnosis

• Sputum or pus should be examined microscopically and by culture for the presence of nocardiae. In pts with nocardial pneumonia, sputum smears are often negative, and bronchoscopy may be needed to obtain adequate specimens.
  • Cultures take 2-4 weeks to yield the organism. To maximize the likelihood of isolation, the laboratory should be alerted if nocardiosis is being considered.
  • Sputum cultures positive for nocardiae should be assumed to reflect disease in immunocompromised hosts, but may represent colonization in immunocompetent pts.
• Discharge from lesions suspected to constitute an actinomycetoma should be examined for granules, the appearance of which can help differentiate this diagnosis from eumycetoma (cases involving fungi) and botryomycosis (cases involving cocci or bacilli).
  • Granules from actinomycetomas consist of fine filaments (0.5-1 µm wide) radiating from a central core.
  • In contrast, granules from eumycetomas have broader filaments (2-5 µm wide) encased in a matrix, and those from botryomycosis consist of loose masses of bacteria.
• Brain imaging should be considered in pts with pulmonary or disseminated disease.