FINAL DIAGNOSIS - Nocardia asteroides complex.
Members of the genus Nocardia have a type IV cell wall composed of meso-diaminopimelic acid, arabinose, and galactose. The original Nocardia isolate came from animals and was described by Nocard in 1888. Nocardia asteroides was isolated from humans a short time later. Nocardia asteroides is taxonomically diverse which is why it is now called Nocardia asteroides complex1. There are six types of Nocardia included in the Nocardia asteroides complex which are characterized based on RFLP analysis of heat shock proteins. The named types of the Nocardia asteroides complex are N. asteroides sensu stricto (type VI), N. farcinica, N. nova and N. abscessus3. Of clinical importance, there are different antibiotic susceptibility patterns among the different members of the complex.
EPIDEMIOLOGY AND DISEASE
Nocardia is a facultative intracellular pathogen. It can live inside of macrophages by inhibiting phagosome-lysosome fusion. Nocardia also inhibits the macrophages from producing catalase and superoxide dismutase, thereby inactivating the myeloperoxidase system of these phagocytic cells1. In the United States, Nocardia asteroides is the most frequently isolated pathogen of the genus Nocardia. It is a saprophytic soil microorganism and is usually acquired through inhalation; however, cutaneous disease may result from direct inoculation following trauma. Cutaneous infections include: mycetoma, lymphocutaneous infection, abscess, cellulitis, and cutaneous involvement secondary to disseminated disease2. Nocardiosis usually occurs in immunocompromised patients. Predisposing factors include immunosuppressive medications, corticosteroids, malignancy, chronic bronchopulmonary disease and AIDS. One of the more common scenarios is a patient with chronic lung disease on long-term steroid therapy3. The patient presented here had lung disease in the form of Wegener's granulomatosis and was immunosuppressed due to Cytoxan and steroid therapy. Most cases of nocardiosis present as pulmonary disease. The infection often disseminates to other sites of the body, including the brain and skin. Approximately 45% of patients with disseminated disease will have central nervous system involvement. These patients have a poor prognosis with 7-44% mortality1.
In this patient, the pulmonary infection appeared first. The patient began treatment with oral trimethoprim-sulfamethoxazole; however, it appears that the patient was taking the wrong dose (three times per week rather than three times per day). He then developed pain in his left knee. Gram stain and culture of the synovial fluid grew Nocardia asteroides. Although Nocardia asteroides frequently disseminates, septic arthritis with Nocardia is fairly uncommon. The first case of Nocardia septic arthritis was described by Baikie et al. in the Lancet in 19704. The second case report of septic arthritis due to Nocardia was described by Rao in 19815. That patient was a renal transplant recipient on immunosuppressive medication. According to Shin and Wilson, only eight cases of Nocardia osteomyelitis have ever been reported. Furthermore, less than 10 cases of septic arthritis with Nocardia have been reported through 2006 6. Although it is quite rare, Nocardia arthritis must be kept in the differential as a cause of septic arthritis, especially in immunocompromised patients.
Sulfa-based antibiotics like trimethoprim-sulfamethoxazole remain the first line of therapy, often used in combination with other antimicrobials3. It is recommended that a sulfa-based drug and another agent such as linezolid or imipenem be used for severe systemic infections7.
LABORATORY DIAGNOSIS AND IDENTIFICATION
Performing a Gram stain on a clinical specimen (in this case, synovial fluid) is the most sensitive method to visualize Nocardia3. Nocardia are gram-positive with thin, beaded, branched filamentous hyphae (see figure 1). The branching occurs at right angles. One can also perform the modified Kinyoun acid-fast stain, which utilizes 1% sulfuric acid as a decolorizing agent.
Nocardia can be grown on routine bacteriologic media including chocolate agar, %5 sheep blood agar and conventional blood culture bottles; however, BCYE agar is the medium of choice. Growth usually occurs within a week, but cultures should be maintained for 2-3 weeks in order to isolate slow-growing Nocardia strains3. Tissue samples usually require longer incubation times. Colonies are often white to yellow or orange with aerial hyphae. A stereomicroscope may be necessary to see the aerial hyphae in the early stages of growth.
As mentioned above, sulfonamides are the therapy of choice; however, susceptibility testing should be performed, especially in severe refractory cases (see Table 1) to ensure proper treatment. Some studies have shown linezolid, a newer antibiotic, has activity against all Nocardia species.2 The patient presented here is stable, but his arthritis and cerebritis are lingering despite appropriate therapy.
Contributed by Deborah Marks-Jones, MD, Ibrahim Batal MD, and William Pasculle, Sc.D
Clinical information contributed by Fernanda Silveira, MD.