Nocardiosis

27-year-old man was admitted to the hospital with a 3-week history of dry cough, anorexia, weakness, and weight loss. The patient was positive for human immunodeficiency virus and was noncompliant with prescribed antiretroviral medications. His CD4 count and viral load were unknown at the time of admission. A chest radiograph revealed diffuse cystic and bullous changes and coarse reticular markings throughout both lung fields, consistent with chronic, most likely postinfectious, fibrotic changes, possibly with a superimposed active infectious process (Figure 1). The patient underwent bronchoscopy and bronchoalveolar lavage. Transbronchial biopsies of the right lower lobe were obtained. Material was submitted for bacterial, fungal, and viral cultures, and for histopathologic examination. Acid-fast bacilli were seen on the smear from bronchial secretions by the auramine-rhodamine method. A presumptive diagnosis of mycobacterial infection was made. Mycobacterium xenopi was subsequently isolated from mycobacterial culture. Routine bacterial, fungal, and viral cultures were negative. Microscopic examination of transbronchial biopsies demonstrated extensive inflammatory infiltrate involving bronchial tissue and expanding adjacent alveolar interstitium. The infiltrate consisted of plasma cells, lymphocytes, histiocytes, neutrophils, and rare multinucleated giant cells (Figure 2, original magnification x400). Well-formed granulomas were not seen. Ziehl-Neelsen stains for acid-fast bacilli were negative. Gomori methenamine silver stain, Gram stain, and modified acid-fast Fite stain (Figure 3, oil immersion, original magnification x 1000) revealed the presence of gram-positive, branching, filamentous, beaded bacteria morphologically diagnostic of Nocardia species.

Nocardia species belong to the group of aerobic bacteria generically designated as actinomycetes. They are ubiquitous environmental saprophytes living in soil, organic matter, and water.' Nocardiae have long been known to cause disease in animals and are being recognized increasingly as opportunistic human pathogens. The organism does not elicit a humoral response and is eliminated from the body via cell-mediated mechanisms. Thus, individuals with impaired T-cell function are at increased risk for nocardial infection. Groups at the highest risk inelude patients who have undergone transplantation surgery or who are receiving steroid or cancer therapy. Nocardia species are uncommon opportunistic pathogens in acquired immunodeficiency syndrome (AIDS), affecting only 0.19% to 0.30% of patients with AIDS.2 Several species are recognized, with Nocardia asteroides accounting for up to 90% of clinically significant isolates. Other species responsible for disease in humans include Nocardia brasiliensis, Nocardia otitidiscaviarum, Nocardia farcinica, Nocardia nova, and Nocardia transualensis. The organism is acquired from the environment by direct inoculation of skin or soft tissues or by inhalation. There is no animal-to-human or human-to-human transmission.' Various species of Nocardia can cause both localized and disseminated disease. The species most commonly isolated from a localized cutaneous form (mycetoma) is N brasiliensis. Lung and the central nervous system are other frequently involved organs. The organism is only rarely isolated from blood, although several cases of Nocardia septicemia, with mortality rates approaching 50%, have been reported. Nocardiae grow on most routine bacterial, fungal, and mycobacterial culture media used in clinical microbiology laboratories; however, in bacterial cultures, they are easily overgrown by other, more rapidly growing organisms from specimens containing normal bacterial flora, such as respiratory tract secretions. Selective media, such as Thayer-Martin agar with antibiotics, can be used to enhance the sensitivity of the culture. The colonies are either pigmented, waxy, and cerebriform or dry and chalky white, and they produce a characteristic musty odor. The organisms are weakly gram-positive and partially acid-fast. The latter feature, combined with a characteristic branching filamentous morphology, allows for presumptive identification of the bacteria. The methods used for definitive identification of isolates include expanded biochemical and susceptibility testing, cell wall analysis by gas-liquid chromatography, and molecular techniques. Unlike fungal hyphae, the nocardia filaments are narrow, measuring approximately 1 [Lm in width. Morphologic characteristics, together with negative routine acid-fast stains (Ziehl-Neelsen, auraminerhodamine), differentiate nocardia from mycobacteria. The significance of M xenopi isolated in this case is unclear.

Partial acid-fastness is a unique characteristic of Nocardia that is not exhibited by other actinomycetes. It can be demonstrated in direct smears by modified Kinyoun stain, in which acid-alcohol decolorizer is substituted with a low-concentration inorganic acid. In paraffin sections, the organism can be visualized by silver stains, tissue Gram stains, or Fite-Ferraco acid-fast stain.

Pulmonary disease is one of the most common manifestations of systemic nocardiosis and an uncommon, but potentially fatal complication of advanced AIDS? Nocardia asteroides is the etiologic agent in the majority of cases. In the lung, the organism usually provokes a suppurative response. Pneumonia, lung abscess, or cavitary disease with spread to contiguous structures are typical clinical presentations. Dissemination of the disease to other organs, most notably brain, occurs in significant numbers of cases. Diagnosis is difficult and commonly delayed. Disseminated disease carries high mortality rates. Sulfonamides are considered the treatment of choice for nocardiosis.1 Amikacin, imipenem, and third-generation cephalosporins show excellent efficacy against some species of Nocardia in vitro and can potentially be used as a first-line or additive treatment. The clinical outcome of therapy is largely dependent on the site and extent of disease.

References

1. Lerner Pl. Nocardiosis. Clin Infect Dis. 1996;22:891-905.

2. Kim J, Minamoto GY, Grieco MH. Nocardial infection as a complication of AIDS: report of six cases and review. Rev Infect Dis. 1991;13:624-629.

Dorota Filipiuk, MD; Elliot Weisenberg, MD; Zbigniew Malecki, MD

Accepted for publication January 19, 2001.

From the Department of Pathology, Advocate Illinois Masonic Medical Center, Chicago, Ill.

Reprints: Elliot Weisenberg, MD, Department of Pathology, Advocate Illinois Masonic Medical Center, 836 W Wellington Ave, Chicago, IL 60657 (e-mail: eweisenberg@immc.org).

Copyright College of American Pathologists Jul 2001
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