Nocardia beijingensis lung mass in an immunocompetent adult

Abstract

A 47-year-old man was referred for ongoing workup of an enlarging lung mass. Extensive workup of the mass had been unrevealing for several months until cultures grew Nocardia beijingensis. He was successfully treated with trimethoprim/sulfamethoxazole and then doxycycline with near-complete resolution of the mass on follow-up. This case presents a rare species of N. beijingensis. It highlights the importance of considering nocardiosis in immunocompetent adults and the challenge in initiating targeted treatment due to delayed culture results.

Background

Nocardia are ubiquitous, aerobic Gram-positive, weakly acid-fast bacilli (AFB) that most commonly affect the lungs, skin, muscle and central nervous system.¹ Although it tends to occur in immunocompromised hosts, approximately one-third of affected patients are immunocompetent.^{1 2} Maintaining a wide differential diagnosis is imperative when presented with a lung mass of unknown origin. We present the case of Nocardia beijingensis that was isolated from a lung mass in an immunocompetent host.

Case presentation

A 47-year-old immunocompetent man presented to a tertiary care hospital for ongoing workup of a left upper lobe lung mass. Four months prior to presentation to our hospital, the otherwise healthy patient presented to the emergency department with new-onset chest pain, diaphoresis and dry cough. Cardiac workup was negative. Due to worsening symptoms, he underwent chest CT which revealed a 4.2 cm×4.7 cm×3.7 cm mass in the left upper lobe that was hypermetabolic on positron emission tomography. The patient had no alcohol, smoking or illicit drug use. He lived on the east coast of the USA; he had never travelled outside of the country. He had previously raised pigs. He had no pertinent family history. On presentation, vital signs were within normal limits. He had good dentition with no oral thrush. He had decreased breath sounds throughout the left lung fields with occasional faint wheezes in the left upper and middle lobes. Right lung examination was normal. There was no cervical, supraclavicular or axillary lymphadenopathy. No peripheral oedema or clubbing were noted. Examination of all other organ systems was unremarkable.

Investigations

The patient underwent several biopsies of the mass by interventional radiology as well as via bronchoscopy which showed focal hyaline-membrane-like material and granulomatous inflammation, respectively, with no identification of malignant cells. Bronchial lavage cultures were negative for bacteria, AFB and fungus. He tested negative for HIV-1 and 2 antibodies. Serologies for Brucella, Bartonella and Coccidioides spp were also negative along with urinary antigen for Histoplasma. Interferon-gamma release assay testing for Mycobacterium tuberculosis was negative. An extensive rheumatologic workup for vasculitis, including cytoplasma and peripheral antineutrophil cytoplasmic antibodies (c-ANCA and p-ANCA) was also unrevealing. Follow-up CT chest imaging 3 months after symptoms onset showed enlargement of mass to 7.5 cm×2.5 cm×5.2 cm for which he underwent a left-sided video-assisted thoracoscopic surgery with growth of normal respiratory flora on bacterial cultures and negative smears for AFB and fungi. Due to consistently negative findings, he was transferred for a higher level of care.

On presentation to our hospital, laboratory studies were notable for a white cell count of 16.8×10⁹/L (3.7–9.7×10⁹/L) and haemoglobin of 10.0 g/dL (12.0–15.0 g/dL). Other routine laboratory tests were within normal limits. He had an elevated erythrocyte sedimentation rate of 68 mm/hour (0–20 mm/hour) and an elevated C reactive protein of >31.7 mg/dL (0–6 mg/L). Serum fungitell was normal (<31 pg/mL). CT chest showed that the mass had enlarged to 11.6 cm×5.5 cm×7.2 cm and now contained several discrete complex gas and fluid collections that infiltrated the superior mediastinum causing mediastinitis with an associated mediastinal abscess. An image of the mass can be seen in figure 1.

Figure 1.

An axial CT image obtained without intravenous contrast enhancement on initial presentation to the tertiary hospital. The mass measured 11.6 cm×5.5 cm×7.2 cm and now contained several discrete complex gas and fluid collections that infiltrated the superior mediastinum causing mediastinitis with an associated mediastinal abscess.

The patient then developed dysphagia for which he underwent an oesophagram that revealed an oesophageal leak from the left lateral aspect of the proximal thoracic oesophagus into the left upper lobe mass with moderate oesophageal dysmotility. Cardiothoracic surgery performed an oesophogastroduodenoscopy that confirmed an oesophageal tear/fistula in the area of the leak along with biopsy of the oesophagomediastinal fistula and left upper lobe lung mass. Due to inconclusive findings on pathology, the patient underwent a CT guided core needle biopsy of the lung mass which finally assisted in determining the final diagnosis. Pathology showed necrotic debris with histiocytes and inflammation consistent with acute necrotising pneumonia with intra-alveolar fibrin. His previous fungal culture was now, 4 weeks later, positive for Nocardia species, subsequently identified as N. beijingensis. The cultures taken from the latest CT guided biopsy also grew N. beijingensis. CT head was negative for central nervous involvement of Nocardia. Neutrophil oxidative burst assay to test for the chronic granulomatous disease (CGD) was performed and was normal. Of note, during the hospitalisation, the patient was also found to have bilateral lower extremity deep vein thrombosis.

Differential diagnosis

In this particular patient, maintaining a wide differential diagnosis was important in helping us arrive at our final diagnosis. Although our patient was young and had no known risk factors for malignancy, this was important to exclude. Pathology of tissue specimens did not reveal any malignant cells making a primary, or metastatic disease, unlikely. Pulmonary vasculitis was also on the differential diagnosis. However, lack of other organ involvement as well as negative antibody testing for common vasculitidies made this an unlikely diagnosis in this patient. Other causes of a mediastinal mass including fibrosing mediastinitis would also have a largely negative infectious workup but pathology of the biopsied specimen would have yielded that diagnosis.

An infectious aetiology of the lung mass seemed most probable given the patient’s demographics and presenting symptoms and finally supported by pathology findings suggestive of an acute necrotising pneumonia. Mycobacterium tuberculosis should always been on the differential in a patient presenting with subacute to chronic symptoms and the finding of a new lung mass. However, our patient had a negative interferon-gamma release assay as well as a negative AFB stain of the biopsy specimen. Endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis, paracoccidioidomycosis) were also high on our differential given the presenting symptoms in a patient who was living in a rural setting. Although serum markers are not the gold standard for diagnosis, a negative Fungitell test can aid in excluding an invasive fungal infection.³ Finally, nocardiosis was also on our differential, as this can occur in immunocompetent individuals and can present with a subacute lung mass. We know that Nocardia are only weakly acid fasting staining, so a negative test did not exclude this from our differential.

Treatment

Patient was empirically placed on intravenous imipenem/cilastin and trimethoprim/sulfamethoxazole (TMP/SMX). He was then transitioned to oral TMP/SMX and doxycycline once N. beijingensis was identified and found to be susceptible to cefepime, ceftriaxone, imipenem, clarithromycin, amikacin, tobramycin, doxycycline, minocycline, TMP/SMX, and linezolid. His oesophageal fistula to the mediastinum was treated conservatively.

Outcome and follow-up

The patient’s presenting symptoms had resolved on outpatient follow-up and a chest CT scan done about 5 weeks after being started on appropriate antibiotics, showed a 30%–40% decrease in the size of the lung mass.

After several weeks of therapy, patient developed intolerance to TMP/SMX after noticing oral pain. He remained on doxycycline monotherapy for the duration of 6 months. He received a 3-month course of anticoagulation with warfarin and then apixaban for his bilateral deep vein thrombosis. Repeat chest CT scan performed 9 months after diagnosis showed near-complete resolution of the lung mass. This is demonstrated in figure 2.

Figure 2.

An axial CT image obtained without intravenous contrast enhancement taken 9 months after initial presentation. This shows near complete resolution of the previously noted lung mass.

Discussion

N. beijingensis was first isolated from the environment in 2001 and the first human case from the USA was described in 2014.^{4 5} Although Nocardiosis is traditionally thought of affecting immunocompromised patients, however, the cases of N. beijingensis reported to date favour immunocompetent individuals.⁶ Since diagnosis is often delayed due to prolonged incubation periods, our case demonstrates that nocardiosis needs to be considered in the workup of all lung masses regardless of the immune status of the patient.

Due to the association with immunocompromise, it is critical to undertake an appropriate workup in patients identified with nocardiosis. CGD is characterised by recurrent fungal and bacterial infections, such as Nocardia, due to reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and inability of macrophages to eliminate catalase-positive bacteria.^{7 8} Although our patient did not have a history of recurrent infections, after cultures confirmed a diagnosis of Nocardia, a neutrophil oxidative burst assay was performed and was negative. Our case highlights the importance of a comprehensive workup for underlying causes of immunocompromise such as HIV and CGD.

Duration of treatment for nocardiosis is often prolonged due to relapsing nature of the infection and depends on the immune status of the patient and the organs involved. Treatment for pulmonary nocardiosis is typically 6–12 months long but central nervous system involvement and immunocompromised patients tend to be treated for at least 1 year.⁹ Due to the rarity of the case, there are no current guidelines on the treatment of N. beijingensis and recommendations are based on expert opinion. Since our patient was immunocompetent and responded quickly to treatment with noticeable shrinkage of the mass on follow-up, we opted for a shorter duration of treatment with 6 months. With improved identification of isolates using molecular techniques, there is a concern for the emergence of antimicrobial resistance among certain species of Nocardia. This is of particular concern given the prolonged treatment duration involved. For this particular species, it is reassuring that it was sensitive to available treatment regimens.¹⁰

Learning points.

• This is a rare case of Nocardia beijingensis identified in an immunocompetent adult man.

• A wide differential diagnosis needs to be maintained in the workup of a lung mass of unknown origin, regardless of the immune status of the patient.

• Based on the few case reports of N. beijingensis, it tends to occur in immunocompetent hosts and appears to be fairly susceptibe to current available regimens.