Multiple rim-enhancing brain lesions and pulmonary cavitary nodules as the presentation of Nocardia cyriacigeorgica in a patient with non–small cell lung cancer

Abstract

Nocardiosis is caused by various strains of the genus Nocardia, a gram-positive, acid-fast bacillus found in organic matter. Disseminated nocardiosis with central nervous system involvement is a rare infection that is most commonly seen in immunocompromised patients. We present a case of a 67-year-old veteran with stage IV adenocarcinoma of the lung undergoing chemotherapy who presented with new cavitary pulmonary lesions. Three weeks into his hospitalization, a sputum culture with acid-fast staining returned positive for Nocardia cyriacigeorgica. A subsequent computed tomography scan of the head demonstrated numerous rim-enhancing lesions presumed to be due to disseminated nocardiosis with central nervous system involvement. Disseminated nocardiosis has a high mortality rate, making prompt detection and treatment paramount for these patients. Our case highlights the importance of considering central nervous system involvement in the evaluation of a patient with nocardiosis.

Nocardiosis is an infection caused by an aerobic gram-positive rod-shaped bacterium that is partially acid fast and characterized by branching filaments on cytology. The genus Nocardia comprises ubiquitous bacteria that can be found in standing water and soil.¹ The bacteria are opportunistic pathogens that primarily cause disease of the lungs but may sometimes affect the skin or central nervous system (CNS). Disseminated nocardiosis is an uncommon but dangerous cause of CNS infection in patients with immunocompromising conditions.² We report a case of disseminated nocardiosis with CNS involvement in a patient with recent chemotherapy use.

CASE DESCRIPTION

A 67-year-old Hispanic man with stage IV adenocarcinoma of the lung involving the pleura and pericardium presented to our hospital following 4 days of dyspnea and productive cough with yellow-colored phlegm. Three months prior, he had been found to have pleural and pericardial effusions. Pericardial fluid was positive for blood and reactive mesothelial cells with atypical hyperplasia; pleural fluid analysis was suggestive of metastatic adenocarcinoma with an immunophenotype suggesting primary lung malignancy. He began chemotherapy with pembrolizumab, carboplatin, and pemetrexed, with his most recent dose 6 days prior to the current admission.

On admission, chest computed tomography (CT) demonstrated multiple new pulmonary lesions with cavitary features and air-fluid levels, most notably within the right lower lobe. There was an additional large area of consolidative change within the left upper lobe measuring around 4.5 cm, which was also appreciated on chest radiograph (Figure 1a, 1b). Pleural fluid cultures from thoracentesis were positive for malignant cells but negative for bacteria. Tuberculosis testing was negative. He completed a 14-day course of piperacillin-tazobactam for possible necrotizing pneumonia. After completion, he developed worsening leukocytosis, and antibiotics were restarted. Original sputum cultures taken on the day of admission returned positive for Nocardia cyriacigeorgica, prompting an evaluation for CNS involvement.

Figure 1.

(a) CT demonstrating pulmonary lesions with cavitary features and air-fluid levels. (b) Chest radiograph with consolidative change within the left upper lobe and multifocal air cavities. (c) CT of the head with rim-enhancing masses with surrounding vasogenic edema.

Head CT revealed 15 to 20 rim-enhancing masses ranging from 6 to 17 mm in diameter with surrounding vasogenic edema concerning for infectious or metastatic disease (Figure 1c). The patient was initiated on intravenous imipenem, ceftriaxone, and sulfamethoxazole/trimethoprim. Treatment options, including a lumbar puncture to establish a definitive diagnosis and guide further therapy, were discussed. However, the patient ultimately decided to transition to hospice care. Corticosteroids were initiated for improvement in comfort. The patient chose to continue antibiotic therapy with sulfamethoxazole/trimethoprim. Repeat CT after discharge revealed improving brain lesions while on antibiotic therapy and without any further chemotherapy, which further supported the diagnosis of disseminated nocardiosis.

DISCUSSION

Nocardia are a cause of pulmonary, skin, and rare CNS infections. Owing to the difficulty culturing this pathogen and the expensive lab techniques required for its growth, timely diagnosis is often difficult to achieve. Our case recapitulates the challenge of making a timely diagnosis of nocardiosis, as N. cyriacigeorgica was isolated on sputum culture 3 weeks into hospitalization. Advances in laboratory analysis and greater awareness of the pathogen have led to earlier detection of the disease and improvement of clinical outcomes. The first case to identify N. cyriacigeorgica within the lungs utilized 16S rRNA gene sequence analysis and was published in 2001.³ The index case of N. cyriacigeorgica sequenced in the blood was in 2006, and the organism was identified in the US 2 years later.^4,5 The recent adoption of matrix-assisted laser desorption/ionization time-of-flight-mass spectroscopy has made some improvements to this process.⁶

Nocardiosis is well described as a pulmonary infection, but its prevalence in the CNS is much more rare. This organism has been described to seed distant sites via hematogenous spread. Nocardia has been found to affect a wide variety of locations in immunocompromised patients including the orbit, spinal/paraspinal structures, heart valves, mediastinum, and joints.^7–13 Our case reflects the severe morbidity and mortality associated with a delay in diagnosis of disseminated nocardiosis. Although the patient chose to pursue hospice care, our case serves as a reminder of the importance of early intervention and appropriate treatment of N. cyriacigeorgica infection with CNS involvement, which includes appropriate antibiotic treatment and neurosurgical evaluation.