Nocardia farcinica infection presenting as a solitary bronchial neoplasm in an immunocompetent adult: a case report

Nocardia species are gram-positive, acid-fast, saprophytic, aerobic bacilli, predominantly resulting in opportunistic infections in immunocompromised individuals. Here, we reported a case of Nocardia infection in a 27-year-old woman with normal immunocompetence, who presented as a solitary neoplasm in the left principal bronchus with a chief complaint of postural dyspnea. By electrotomy via bronchoscopy, the neoplasm was successfully removed, and it was further identified as Nocardia farcinica by metagenomic next-generation sequencing.


Introduction
Nocardia species are gram-positive, acid-fast, saprophytic, aerobic bacilli, widely found in soil, decomposing vegetation, and other organic matter (1).Among all of the Nocardia species, Nocardia asteroides, Nocardia brasiliensis, and Nocardia otitidiscaviarum were documented to be the most common pathogenic strains (2), predominantly causing opportunistic infections in immunocompromised individuals (3).However, in the present report, we described a case of Nocardia farcinica infection in an immunocompetent adult, presenting as a solitary neoplasm in the left principal bronchus with a chief complaint of postural dyspnea.

Case presentation
A 27-year-old woman was admitted to the local hospital because of recurrent dyspnea while in the left lateral decubitus position for 3 weeks.No other symptoms such as fever, cough, wheezing, expectoration, hemoptysis, and chest pain were reported.Moreover, she had a history of surgery in the right talus due to cartilage damage 5 months ago and denied any history of asthma, bronchiectasis, pulmonary tuberculosis, allergic diseases, anemia, autoimmune diseases, acquired immune deficiency syndrome, and tumors.On physical examination, no positive signs were revealed.The timeline of history for the present illness  was showcased in Figure 1.In laboratory tests, the interferon-gamma release assay was positive, but the tuberculin skin test was negative.Furthermore, there were no positive results in the blood routine examination, antinuclear and anti-neutrophil cytoplasmic antibody test, and human immunodeficiency virus antibody test (Table 1).Importantly, chest tomography (CT) displayed a small hyperdense nodule of approximately 5 mm × 6 mm in the left principal bronchus with mild intensification in the enhanced images (Figures 2A,B).No significant lesions were detected in the mediastina, lung lobes, and pleural cavities.By endotracheal endoscopy, a smooth-surfaced neoplasm with airway obstruction was visualized in the left principal bronchus (Figure 2C).Subsequently, the neoplasm was successfully removed with electrotomy (Figures 2D,E), and pathological biopsy with metagenomic next-generation sequencing (mNGS) was then carried out for precise diagnosis.
Overall, the patient was definitely diagnosed with Nocardia farcinica infection localized in the left principal bronchus.Moreover, since no clinical evidence supported the possibilities, tuberculosis and tumors were excluded.After removal of the neoplasm and during the follow-up, the patient had no more dyspnea.Therefore, no antibiotic therapy was administrated all the way.This case report was approved by the Institutional Review Board of West China Hospital of Sichuan University, and the informed consent was obtained.

Discussion
Nocardia species highly opportunistic pathogens and typically cause infections in immunocompromised individuals (6-9).Unlike the other strains, Nocardia farcinica often exhibits pulmonary infection via inhalation with a greater propensity for dissemination and a unique pattern of antibiotic susceptibility (10).Consequently, it is prone to develop into severe pneumonia or sepsis, leading to a deteriorating prognosis (11,12).
However, it has been reported that pulmonary infection by Nocardia farcinica may occur in immunocompetent subjects (Table 3) (13-16).Although these reported cases typically presented with fever, cough, and expectoration, as well as leukocytosis and elevated C-reactive protein (CRP), radiological findings usually demonstrated the localized presence of nodular shadows and pleural effusion, which was more easily recovered after antibiotic treatment.Differently, this patient, an immunocompetent host, complained of postural dyspnea but no fever and other respiratory symptoms, and the Nocardia farcinica infection was strictly limited within the left principal bronchus, presenting as a solitary neoplasm.
The precise identification of Nocardia species has been challenging.In the past decades, traditional methods including microscopic examination, microbial culture, and biochemical analyses were widely used, but with more false-negative results than expected (17,18).Subsequently, 16S rRNA sequencing seems to improve the testing efficiency; however, this technique might miss the potential non-bacterial infections that are usually considered depending on the clinical assumption (19,20).More importantly, the clinical presentation of this patient was so atypic that we could not exclude the possibility of non-bacterial  infections.Thus, for this case, rRNA sequencing may not be the best choice for microorganism identification, and relatively, mNGS is a more ideal method that, regardless of clinical assumption, identifies pathogenic microorganisms/Nocardia strains comprehensively, quickly, and accurately, providing an opportunity for precise interventions at the early stage (21)(22)(23).
As demonstrated in this case, the significant presence of Nocardia farcinica was detected by mNGS from the resected tissue, which confirmed its pathogenic role according to the Johns Hopkins ABX Guide (24).However, it should be noted that mNGS reports must be cautiously interpreted before accurate differentiation of pathogenic, contaminated, and colonized subgroups (19).Moreover, antimicrobial therapy plays a key role in the treatment of Nocardia infections.Trimethoprim-sulfamethoxazole (TMP-SMX) is the most recommended antibiotic, usually combined with imipenem and amikacin (25).However, as suggested in this case, antibiotics are not always necessary to treat the localized infections, but surgical resection can bring about a significant improvement and recovery.

Conclusion
Overall, this case report indicates (i) immunocompetent individuals are the target for pulmonary infection by Nocardia, which may present as atypical manifestations and localized lesions; (ii) adoption of mNGS can benefit for accurate identification and early diagnosis of Nocardia infections; and (iii) surgical management but not antibiotic therapy could be the first choice for these patients with localized lesions.

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FIGURE 1
FIGURE 1Timeline of the patient's history of present illness.

FIGURE 2 (
FIGURE 2 (A) Chest tomography (CT) displayed a small hyperdense nodule (red circles) in the left principal bronchus, and (B) mild intensification was detected in the enhanced CT image.(C) Bronchoscopy visualized a smooth-surfaced neoplasm with airway obstruction in the left principal bronchus, and (D) it was excised with electrotomy and (E) removed successfully.(F) HE stain showed chronic active inflammation with histiocyte aggregation.

TABLE 1
Results of laboratory tests.

TABLE 2
Results of metagenomic next-generation sequencing.