Nocardia cyriacigeorgica: An unusual etiological agent of brain abscess in a patient with myeloma

INTRODUCTION

Nocardiosis is an opportunistic infection caused by weakly Gram-positive, partially acid-fast, filamentous, branching, aerobic bacteria of the genus Nocardia, which belongs to aerobic actinomycetes. Over 100 species under the genus Nocardia are ubiquitously available in water and soil; more than 40 are clinically relevant, causing human infections via inhalation or direct inoculation into the skin.^[1-3]

Extrapulmonary nocardiosis can affect skin, subcutaneous tissue, and the central nervous system (CNS); in fact, it can occur anywhere in the body as a result of dissemination from primary pulmonary disease, which is the most common clinical presentation.^[4] In CNS nocardiosis, the disease can be clinically silent and may be misdiagnosed as primary tumors or other space-occupying lesions or metastatic lesions on imaging rather than infection.^[2] Here, we present a case of a nocardial brain abscess secondary to pulmonary nocardiosis in a patient with multiple myeloma.

CASE REPORT

A 70-year-old male was diagnosed with lambda myeloma in October 2023 and was given four cycles of a triplet chemotherapy regimen consisting of bortezomib, lenalidomide, and dexamethasone, after which he achieved complete remission. The patient presented with a productive cough and cold on the current admission on 11^th January 2024. On examination, the patient was found to have slurring of speech with facial swelling. All test reports were found within normal limits except C-reactive protein, 20.9 mg/dL, and X-ray chest showing mild haziness in the right paracardiac location [Figure 1] and high-resolution computed tomography of the chest, which showed nodular lesions suggestive of infective etiology [Figure 2a and b]. The patient was prescribed intravenous piperacillin-tazobactam, oral clarithromycin, and oral posaconazole as part of the treatment regimen. The patient showed improvement and hence discharged on oral antibiotics and antifungals on 16^th of January.

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Figure 1:

Chest X-ray - Mild haziness in the right paracardiac location likely represents consolidation.

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Figure 2:

High-resolution computed tomography chest (a) bronchial wall thickening with hypodense contents in the right middle lobe bronchus - infective etiology, (b) Patchy subpleural collapse - consolidation in the right middle lobe.

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On 23^rd January, the patient was re-admitted for routine chemotherapy. There was no history of fever, convulsions, or altered sensorium. On examination, there was deviation of the tongue to the left side with right limb weakness with power grade 2/5; lung sounds were found to be clear. His routine laboratory investigations and cerebrospinal fluid obtained by lumbar puncture were unremarkable. Chest X-ray revealed fibrotic opacities in the lower right zone of the lung. Bronchoalveolar lavage (BAL) was processed for Gram stain, fungal stain, aerobic culture, and cartridge-based nucleic acid amplification test; no specific pathogen was identified. The BAL sample was also processed on Sabouraud’s dextrose agar (SDA) slants. Magnetic resonance imaging (MRI) brain revealed heterogeneous lesions in the frontal lobes with perilesional edema [Figure 3].

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Figure 3:

Magnetic resonance imaging Brain: Axial T2-weighted image demonstrates two heterogeneously hyperintense, conglomerated ring-enhancing cystic lesions in the left frontal lobe (13 mm × 16 mm and 5.1 mm × 6.4 mm), associated with significant perilesional edema. The larger lesion shows peripheral blooming on susceptibility-weighted imaging, suggestive of hemorrhagic components.

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A brain biopsy was performed from one of the intracranial lesions, which revealed purulent material. Gram stain of the aspirated pus revealed Gram-positive, unevenly stained, thin, filamentous, branching bacteria in the background of many polymorphonuclear leukocytes [Figure 4a]. Modified Ziehl-Neelsen staining of the pus showed thin, filamentous, branched, partially acid-fast bacteria suggestive of Nocardia species [Figure 4b]. Growth was obtained on blood agar and Lowenstein-Jensen media after 72 hours of incubation at 37°C [Figure 4c and d]. Smears from culture also revealed Gram-positive, partially acid-fast filaments. The growth was confirmed by matrix-assisted laser desorption ionization time of flight (MALDI-TOF MS) Mass Spectrometry (BioMérieux France) as Nocardia cyriacigeorgica. Subsequently, the BAL sample, sent for fungal culture, showed the presence of a similar organism after 2 weeks of incubation.

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Figure 4:

(a) Gram stain showing Gram-positive filamentous branching bacilli (marked with arrow), (b) Modified acid-fast stain showing acid-fast filamentous branching bacilli (marked with arrow), (c) Dry, wrinkled, chalky-white colonies seen on blood agar, and (d) colony on Lowenstein-Jensen media.

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The patient was administered intravenous imipenem and trimethoprim-sulfamethoxazole (TMP-SMX), resulting in significant clinical improvement with enhanced muscle power and reduced slurring. After a 3-week inpatient treatment regimen, the patient was discharged on oral minocycline and TMP-SMX. Thorough maintenance, interspersed with consolidated therapy with imipenem for 10 days every month, was continued for 9 months. He also received 18 cycles of the triplet chemotherapy regimen and continued to be in complete remission after that. Sequential MRI showed progressive reduction of the lesion with complete resolution after the end of 9 months of treatment [Figure 5].

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Figure 5:

Magnetic resonance imaging brain: Follow-up T2-weighted image reveals a markedly reduced, hypointense lesion in the left frontal region (6 mm × 3 mm × 7 mm) with no significant enhancement, minimal surrounding edema, and absence of diffusion restriction.

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DISCUSSION

Laboratory isolation of Nocardia is often challenging due to its slow growth and the presence of numerous commensals in respiratory samples.^[5,6] In the present case, initial diagnosis of pulmonary nocardiosis was not considered due to the absence of detectable Nocardia organisms on both staining and aerobic culture. However, upon extending the incubation period to 2 weeks on SDA, Nocardia was successfully isolated.

Pulmonary nocardiosis and disseminated forms of the infection are opportunistic diseases occurring mainly in immunocompromised patients, including those with solid organ transplant and hematopoietic stem cell transplant recipients, HIV infected patients, or patients with ongoing malignant processes. The dissemination can affect various extrapulmonary sites, with the CNS being most commonly affected, presenting with acute or subacute neurological symptoms.^[3,6-8] Hence, CNS nocardiosis should be considered in the differential diagnosis of CNS lesions, primarily in immunocompromised patients.^[5] Approximately 25-40% of patients with systemic nocardiosis develop CNS infections; abscesses due to CNS nocardiosis result in mortality rates of 20% in immunocompetent patients and approximately 85% in immunocompromised patients, respectively.^[6] These abscesses are often misdiagnosed as primary tumors or other space-occupying lesions or metastatic lesions on imaging.^[6-10] In the present case, the initial differential diagnosis was that of a metastatic brain lesion. Stereotactic brain biopsy and aspiration revealed Gram positive, acid-fast filamentous branching organism, which provided a presumptive diagnosis of Nocardia. Colony morphology on SDA was suggestive of the same organism; this was subsequently confirmed by MALDI-TOF as N. cyriacigeorgica, which belongs to the Nocardia asteroides complex (NAC), drug resistance pattern type VI. A case report by Arjun et al. also states that the most common cause of Nocardiosis worldwide is the members of the NAC.^[9]

There is currently no standard treatment protocol for disseminated nocardiosis because of its infrequent and varied clinical presentation. As resistance is noted with a variety of Nocardia isolates, the treatment plan of disseminated Nocardiosis involves combinations of two to three anti-Nocardia agents.^[10] Sulfonamides remain the drug of choice for all forms of Nocardia. The antibiotics most frequently used in the literature are cotrimoxazole, amikacin, and imipenem. In view of that, initially, the patient was administered cotrimoxazole along with imipenem for 3 weeks. The patient showed clinical improvement regarding CNS symptoms, similar to the study by Duggal and Chugh.^[8] Infections caused by Nocardia species tend to relapse due to their slow replication; hence, prolonged therapy for several months, along with close monitoring of the patient’s clinical response and potential drug toxicity, is required.

CONCLUSIONS

A high index of clinical suspicion of CNS Nocardiosis in immunocompromised patients with CNS symptoms can help in early diagnosis and prompt treatment. The approach to treatment of CNS nocardiosis prioritizes the use of anti-nocardia agents with good penetration of the blood-brain barrier, while certain other agents might be helpful for pulmonary nocardiosis. Prolonged antimicrobial therapy, along with close monitoring, is required to prevent relapses in immunocompromised patients.