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FINAL DIAGNOSIS:
Aerobic blood culture, bronchoalveolar lavage, and synovial fluid cultures were positive for Nocardia farcinica.
BAL culture also grew rare Aspergillus sp.
HISTORY:
In 1888, Dr. Edmund Nocard isolated an aerobic actinomycete from cattle with bovine farcy (pyogenic pulmonary and subcutaneous infections), which was subsequently identified as Nocardia farcinica. Nocardia farcinica is a gram positive, partially acid fast, filamentous bacilli, and is considered an opportunistic pathogen. Nocardia species are exogenous; that is, they are caused by organisms that are not part of the normal human flora. It is found in soil, decaying vegetation, and ventilation systems. Nocardiosis is defined as an acute, subacute, or chronic disease, which usually begins in the respiratory tract. The disease manifestations include fever, a productive mucopurulent cough, and non-resolving infiltrates on chest radiographs. From the lungs, hematogenous dissemination occurs in 50% of patients. Metastatic brain abscesses develop in about 1/3 of patients resulting in headaches, altered mental status, focal neurologic deficits, and seizures. In spite of hematogenous spread, blood cultures and cerebral spinal fluid cultures invariably fail to demonstrate the organism.
The organism is acquired by inhalation (pulmonary), traumatic introduction (cutaneous), and opportunistic exposure (ocular). NAC cause bronchopulmonary disease in immunocompromised patients with a high predilection for hematogenous spread to the central nervous system and skin. Patients at greatest risk are those with T-lymphocyte deficiencies (malignancies and acquired immunodeficiency), those on immunosuppressive therapy (corticosteroids and transplant recipients), and individuals with chronic pulmonary disease (bronchitis, emphysema, asthma, bronchiectasis, and alveolar proteinosis). The diagnosis of Nocardia species infection should be considered when an immunocompromised patient develops pneumonia with cavitation, particularly if there is evidence of dissemination to the central nervous system or subcutaneous tissue.
IDENTIFICATION:
Nocardia farcinica has the ability to grow at 45° Celsius and resistance to erythromycin, cefotaxime, and tobramycin is a common feature for this organism. These characteristics help to distinguish N. farcinica from N. asteroides. If isolation is performed on Middlebrook agar, Nocardia farcinica will result in opacification; while all other Nocardia species are negative.
Histologically, Nocardia has delicate (< 2 microns in thickness) filaments with pronounced branching (Figures 3 & 4). Actinomyces in contrast has a similar filamentous appearance, albeit with slightly thicker, straighter, and less-branched filaments. Since the histologic appearance of Nocardia is similar to other Actinomycetes family members, culture and biochemical testing is necessary for definitive diagnosis/identification. The University of Pittsburgh Medical Center-Presbyterian Department of Microbiology section of Mycology performs isolation of aerobic actinomycetes. The presumptive isolation of gram-positive bacilli with filamentous branching should warrant this culture process. The specimen is cultured onto Tap water agar, which is a nutrient poor media that most other bacteria can not grow. Nocardia species show branched filaments and eventually develop aerial hyphae. Preliminary biochemical tests for differentiation and speciation of Nocardia from the other Actinomycetes genera require 14 days, and include the presence or absence of the following biochemical characteristics: (1) hydrolysis of casein, tyrosine, and/or xanthine (Figure 5: which shows the presence of hydrolysis at the arrow heads), (2) presence of urease, (3) utilization of rhamnose, and (4) positive resistance to lysozyme.
In the case of Nocardia farcinica, there is absence of hydrolysis of casein, tyrosine, and xanthine (Figure 6: absence of hydrolysis) assists in speciation. The next step in the process is antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method to identify Nocardia asteroides complex isolates. The susceptibility testing on the Nocardia farcinica organism isolated from the aerobic blood culture bottle was performed by the University of Texas Health Center at Tyler using a broth microdilution minimal inhibitory concentration (MIC) method.
| ANTIBIOTIC | SENSITIVITY | Kanamycin | RESISTANT | Amikacin | Sensitive | Tobramycin | RESISTANT | Gentamicin | RESISTANT | Doxycycline | RESISTANT | Cefotaxime | RESISTANT | Sulfamethoxazole | Sensitive< | Amoxicillin/clavulanate | Sensitive | Imipenem | Sensitive | Ciprofloxacin | RESISTANT | Minocycline | Intermediate | Ceftriaxone | RESISTANT | Clarithromycin | RESISTANT | Linezolid | Sensitive | Moxifloxacin | Intermediate |
DISCUSSION:
As a transplant recipient with multiple episodes of high-grade rejection, this patient was at increased risk of an opportunistic pathogen, including Nocardia species. The most important being immunosuppression from high dose corticosteroid therapy as well as the presence of his anti-rejection medications, tacrolimus (Prograf) and mycophenolate mofetil (CellCept), which inhibit T-lymphocyte activation and B- and T-lymphocyte proliferation, respectively. These medications render the patient with an acquired T-lymphocyte deficiency.
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Based on the susceptibility testing the patient was treated with trimethoprim/sulfamethoxazole and has since had subsequent chest radiographs (Figure 7) and CT scans that have shown an interval decrease in the size and number of pulmonary nodules. The current management plan is to treat the patient for 6 months, which falls in line with current recommendations for this organism.
REFERENCES:
Contributed by Maurice R. Grant, MD, A. William Pasculle, ScD, and James Shaeffer, MS
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