Nocardiosis is a rare opportunistic infection caused by aerobic, gram-positive bacteria with a filamentous and branched appearance, partially acid-alcohol resistant, belonging to the genus Nocardia [¹]. It affects approximately 500–1000 individuals annually in the United States, according to the Centers for Disease Control and Prevention [²]. Nocardiosis manifests in localized or disseminated forms, with pulmonary nocardiosis being the most common presentation. This typically includes pneumonia, lung abscesses, endobronchial masses, or cavitary lesions [³]. Disseminated nocardiosis, particularly central nervous system (CNS) involvement, represents a life-threatening associated with high mortality and relapse rates, especially among immuno-compromised individuals [⁴]. Although Nocardia can infect both immunocompetent and immunocompromised individuals, the disseminated disease is more common in immunocompromised individuals, particularly in sarcoidosis patients on long-term corticosteroid therapy. While corticosteroids are effective in managing sarcoidosis symptoms, their prolonged use leads to side effects such as weight gain, insulin resistance, and increased susceptibility to infections. This report highlights a unique case of pulmonary nocardiosis in a sarcoidosis patient, with no prior cases documented simultaneous lung, brain, and spinal cord involvement in such patients. The report aims to concisely review this rare and challenging condition’s clinical, pathogenetic, and diagnostic features.

A 46-year-old Caucasian male with a significant past medical history of chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease (GERD), hypothyroidism, and sarcoidosis presented to the emergency department with a three-day history of cough and fever. His current medications included Advair, Proventil, prednisone (50 mg daily for two months), Synthroid, Nasacort, and Prilosec.

Nocardia spp are gram-positive bacilli that form branching hyphae, non-spore-forming, and weakly acid-fast bacteria. Nocardia is a rare opportunistic infection that occurs mainly in patients with low immunity, such as chronic corticosteroid users, organ transplant recipients, and HIV/AIDS patients; however, it may also occur in immunocompetent patients. Infection with Nocardia can occur due to inhalation, which is the most common route, presenting with pneumonia, lung abscess, and cavitary lesions) or through direct inoculation of the skin, which causes cutaneous nocardiosis-cellulitis and ulcers, alongside the infection may then spread to the bones, joints, heart, kidneys, brain, and eyes [³]. Disseminated Nocardia is a life-threatening condition that mainly occurs in severely immunocompromised patients with a mortality rate of up to 85%. It begins as pulmonary Nocardiosis, then involves other organs, which, like our patient, starts as left pneumonia and then disseminates to the brain as multiple abscesses and the spinal cord as an epidural abscess at T4-T5 [⁵]. A few case reports describe sarcoidosis with disseminated nocardiosis on long-term corticosteroids [⁶,⁷,⁸,⁹,¹⁰,¹¹,¹²]. Our patient is unique as no cases have documented simultaneous involvement of the lungs, brain, and spinal cord in such patients. Patients who have underlying structural lung illness are more likely to develop pulmonary nocardiosis [¹³]. Our patient, reported in this case, has a history of sarcoidosis, which probably contributed to him being more vulnerable to primary pulmonary nocardiosis. He was also immunocompromised on chronic prednisone therapy, which rendered him more susceptible to the illness spreading to his brain and spinal cord through the bloodstream. Our patient presented nonspecific symptoms such as cough and fever, which occur with other respiratory organisms. This led to the initial diagnosis of community-acquired pneumonia without suspicion of pulmonary nocardiosis. The clinical manifestations of a Nocardia spp. Pulmonary infections are similar to those of pulmonary tuberculosis (fever, cough, chest pain, night sweats, weight loss, and pneumonia); therefore, the nonspecific feature of the clinical symptoms, as well as the challenge of isolating the organisms in the laboratory, lead to delayed of diagnosis of nocardiosis [³]. Early diagnosis and treatment are essential in patients with nocardiosis. Diagnosis typically requires the organisms to be detectable in smears or sections examined under a microscope, and their isolation and identification are done through microbiologic culture. Sputum smear results are frequently negative. Nocardia species are identified using a modified acid-fast stain containing 1% sulfuric acid, where the bacilli appear as pink filament branching hyphae [³,⁵]. Mass spectrometry and other modern molecular biology technologies, especially PCR and 16S rDNA sequencing, could accurately and rapidly identify Nocardia species [³]. In our case, the blood, sputum, and urine cultures were negative when present on admission. On the 6 days of discharge, the patient’s symptoms increased and presented with worsening cough, sputum production, shortness of breath, and left-sided chest pain, which led us to do an excisional biopsy to confirm the diagnosis and proper management of the patient. On the 13 days of discharge, the patient presented with severe back pain, paraparesis, and urinary retention, which demonstrated the significance of doing a brain MRI on every patient diagnosed with nocardiosis as most of the patients with CNS nocardiosis had no neurological symptoms [¹¹]. The severity of this case highlights that they need prophylaxis against nocardiosis. Some studies suggest prescribing Trimethoprim-sulfamethoxazole as prophylaxis in patients with immunocompromised [¹⁴]. The patient, in this case, was receiving prednisone (50 mg daily for two months, which made him need prophylaxis. For the treatment of nocardiosis, trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice [¹⁵]. However, the Treatment of Nocardia should be guided by Nocardia speciation and susceptibility testing. Non-severe pulmonary nocardiosis and cutaneous infections can be treated with TMP/SMX monotherapy. In the case of sulfa allergy or resistance, another drug like amikacin, imipenem, meropenem, ceftriaxone, cefotaxime, minocycline, moxifloxacin, levofloxacin, linezolid, tigecycline, and amoxicillin-clavulanic acid can be used. The choice of alternative antibiotics should be guided by in vitro susceptibility data in case of immunocompromised patients or those with disseminated disease or CNS involvement; it is recommended that TMP/SMX be administered together with meropenem, imipenem or amikacin. Initial combination therapy is better than TMP/SMX alone as it showed that antibiotic susceptibility patterns of Nocardia spp isolated from the United States of America revealed that more than 50% of isolates were resistant to TMP/SMX. Duration of therapy depends on the patient’s immune state and the lesion’s location; it is recommended for at least 4 to 6 months in pulmonary nocardiosis, 3M in a skin lesion, and 12m in CNS involvement [³,¹⁵,¹⁶]. Our case was first treated with ceftriaxone and azithromycin when cough and fever were present. After confirmation of diagnosis with Nocardia, the treatment was changed to TMP/SMX. However, the Nocardia disseminates to the brain and spinal cord; the treatment changed to IV antibiotic therapy. This case underscores the importance of considering Nocardia infection in immunocompromised patients and those with pre-existing structural lung disease. Brain imaging should be performed in suspected or confirmed nocardiosis cases, as many patients with CNS involvement lack neurological symptoms. Prompt diagnosis and treatment are crucial to avoid severe complications.

This is the first reported case of Nocardia affecting the lungs, brain, and spinal cord simultaneously. Clinicians should maintain a broad differential diagnosis when assessing new pulmonary infiltrates in sarcoidosis patients. Additionally, early CNS imaging is advisable in severe pulmonary nocardiosis to prevent devastating outcomes.