Disseminated Infection of Nocardia farcinica in an Immunocompetent Adult: Mistaken for Tuberculosis Bacilli in Acid-Fast Staining of Bronchoalveolar Lavage Fluid.

Nocardiosis is a kind of infection led by opportunistic pathogens that generally develop in immunocompromised patients. The most usual species causing nocardiosis in humans include Nocardia farcinica, Nocardia nova complex, Nocardia otitidiscaviarum, Nocardia brasiliensis, Nocardia abscessus complex, and Nocardia cyriacigeorgica. The most common manifestation is pulmonary nocardiosis with concomitant extrapulmonary disease occurring due to hematogenous dissemination or contiguous spread from the primary site of infection.[1] Given the rarity of nocardiosis, nonspecific symptoms of the disease, and the need for a longer culture period, appropriate diagnosis and antimicrobial therapy are delayed easily.[23456] However, molecular biological and genetic methods provide greater accuracy for the identification of Nocardia species compared with conventional laboratory procedures. As partially acid-fast branching bacteria, sometimes, acid-fast stained specimens can provide clues and remind us to screen for Nocardia. Morphological description of Nocardia mostly focused on characteristics in Gram stain specimens, in which Nocardia presented with a mass of beaded, filamentous gram-positive Nocardia organisms, and the morphological feature of N. farcinica has never been described separately in the literature. Herein, we report the rare disseminated infection of N. farcinica in an immunocompetent adult, which was detected accidentally by acid-fast staining of bronchoalveolar lavage fluid. Because of the unique morphological characteristics of N. farcinica, it was misdiagnosed as tuberculosis for a long time in the previous few hospitals.

A 55-year-old man presented with fever, cough, expectoration, chest pain, and depressed mood. The patient was previously diagnosed with tuberculosis by three hospitals mainly due to acid-fast stained positive bacilli detected in the bronchial lavage fluid, but bacterial culture was not confirmed, and no significant effect had been achieved in antituberculosis treatment. Acid-fast stain of bronchoalveolar lavage fluid showed acid-fast positive bacteria similar to tuberculosis bacilli; however, most of it presented with longer, thicker, and hyphae-like branching at 90° compared with tuberculosis bacilli (Figure 1b and c: N. farcinica; d: tuberculosis bacilli). Chest computed tomography (CT) showed patchy abnormal density shadows in the upper lobes of both lungs, thus suggesting the infection of both lungs [Figure 1a]. Brain magnetic resonance imaging (MRI) images revealed abnormal lamellar signals in bilateral cerebellum, which were in accordance with the infection of bilateral cerebellum [Figure 1e]. The morphological characteristics of bacteria and the patient's history of disease reminded us to screen for nocardiosis. Subsequently, prolongation of bacterial culture time in bronchoalveolar lavage fluid and nucleic acid sequence of microorganisms in cerebrospinal fluid were suggested. The culture of bronchoalveolar lavage fluid was positive for N. farcinica. And N. farcinica in cerebrospinal fluid was detected by gene sequencing technology, and no mycobacterium tuberculosis was detected. The patient was treated with oral trimethoprim/sulfamethoxazole (TMP/SMX) after the diagnosis was rendered. After 2 months of TMP/SMX monotherapy, the patient recovered from fever, and the CT scan of chest showed a marked reduction of the lesion.

Figure 1

Acid-fast stain of bronchoalveolar lavage fluid showed acid-fast positive bacteria similar to tuberculosis bacilli; however, most of it presented with longer, thicker, and hyphae-like branching at 90° compared with tuberculosis bacilli (b and c: N. farcinica; d: tuberculosis bacilli). Chest CT showed patchy abnormal density shadows in the upper lobes of both lungs, thus suggesting the infection of both lungs. (a) Brain MRI images revealed abnormal lamellar signals in bilateral cerebellum, which were in accordance with the infection of bilateral cerebellum (e)

We present a case of disseminated infection of N. farcinica in an immunocompetent adult without chronic lung disease. The clinical presentation of nocardiosis was nonspecific, chest CT normally revealed lesions in the superior lobe, and brain MRI images commonly showed infection of bilateral cerebellum, which are usually attributed to other reasons, delaying the accurate diagnosis. Microscopic investigation is useful for the diagnosis of nocardiosis. The method of weekly acid-fast staining can be used for the identification of Nocardia. However, affected by decolorization time and specimen thickness on smears, false-negative or false-positive results tend to occur, and these may lead to a misdiagnosis or delay in diagnosis.

Herein, for the first time, N. farcinica was discovered accidentally by acid-fast staining of bronchoalveolar lavage fluid due to its unique morphological characteristics, although misdiagnosed as Mycobacterium tuberculosis infection by several previous hospitals. Compared with the other species of the genus, which present as a mass of beaded, filamentous Nocardia organisms, N. farcinica is shorter, thicker, and present with hyphae-like branching at 90°. According to the reported cases of infection with N. farcinica, it seems to be more disseminated and severe than infection by other species of the genus.[2] We speculate that the clinical features are related with the unique morphological characteristics of N. farcinica, which enable it to spread easily through hematogenous dissemination or contiguous spread from the primary site of infection. Besides, due to the morphological characteristics of N. farcinica, it is easy to be misdiagnosed as Mycobacterium tuberculosis, especially for acid-fast staining positive N. farcinica. Therefore, if acid-fast staining of bacteria is positive, the morphological characteristics should be carefully identified to screen for Nocardia, especially for N. farcinica. When Nocardia is a consideration, longer incubation to ensure optimal culture conditions, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) test, and sequencing of partial 16S ribosomal RNA (ribonucleic acid) should be performed to identify Nocardia at the species level.

In conclusion, as a rare disease, nocardiosis should be attached great importance in the differential diagnosis of infections, not only in immunosuppressed patients but also in immunocompetent patients and those without chronic lung disease. When one kind of bacteria is positive for acid-fast staining, Nocardia should be screened, especially if presenting with hyphae-like branching at 90° compared with tuberculosis bacillus. It is vital for correct diagnosis and prompt and effective treatment.

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Ethical approval

Informed consent has been obtained by the authors.

Financial support and sponsorship

Fundamental Research Plan of Qinghai Province (2018-ZJ-743).

Hebei Province Medical Science and Research Key Project (20200823).

Conflicts of interest

There are no conflicts of interest.