Nocardia farcinica Brain Abscess in a Glucocorticoid-Treated Patient with Giant-Cell Arteritis: A Case Report

Introduction

Nocardia species are gram-positive actinomycetes commonly found in soil and water. Since their initial discovery, the number of identified Nocardia species has grown steadily, with over 100 species currently recognized [1]. Among these, 54 species are clinically significant [2]. Regarding species distribution from patient samples, there is a variability between countries. N. farcinica was the most observed species in China [3] and Japan [4]. N. nova complex and N. brasiliensis were mainly observed in the United States of America [5]. In recent years, molecular analysis, including PCR and 16S rRNA, has improved the identification of Nocardia species [6]. Infections caused by Nocardia in humans are relatively rare. The pathogen enters the body through inhalation or skin lesions. It primarily affects immunocompromised individuals, particularly those undergoing immunosuppressive therapy or those with underlying conditions such as acquired immunodeficiency syndrome. Approximately 10% of Nocardia infections are estimated to occur in patients with no identifiable underlying disease or immunosuppressive treatment.

Nocardia infections can present with variable clinical presentations such as pulmonary, cutaneous, or disseminated diseases. Central nervous system (CNS) nocardiosis typically results from hematogenous dissemination, especially in patients receiving glucocorticoids or following organ transplantation. CNS nocardiosis presentation is often nonspecific (deficits, seizures, motor weakness [7]), but the absence of symptoms cannot exclude the diagnosis [8]. Neuroimaging and cerebrospinal fluid analysis are often necessary for diagnosis. Nocardia can be identified through culture or molecular analysis [2], but the growth speed is slow, increasing the risk of overgrowth by other bacteria. Nocardiosis should be suspected based on the patient’s medical history (eg, glucocorticoid use, chronic lung disease) and environmental factors (eg, occupational exposure). Common sites of infection include the lungs, skin, and brain [1].

Giant-cell arteritis (GCA), formerly known as temporal arteritis, is the most common systemic vasculitis in individuals aged ≥50 years. It is defined as a granulomatous arteritis that affects large- and medium-sized arteries, with a predisposition to involve the cranial branches of the carotid artery but also capable of affecting extracranial large vessels [9]. GCA frequently occurs concomitantly with polymyalgia rheumatica (PMR), reported in approximately 16–21% of cases [10]. Clinical manifestations include headache, constitutional symptoms, jaw claudication, scalp tenderness, and visual disturbances, the latter being particularly critical due to the risk of irreversible vision loss. The standard method for diagnosing GCA is temporal artery biopsy [11]; however, due to its invasiveness and variable sensitivity, noninvasive imaging modalities such as ultrasound and positron emission tomography-computed tomography (PET-CT) are increasingly recommended [12]. High-dose glucocorticoids remain the mainstay of treatment, although tocilizumab (TCZ) has recently been recommended as an additional option [13].

To our knowledge, Nocardia infection in the setting of giant-cell arteritis (GCA) has only been reported in a few cases. Given that GCA primarily affects elderly individuals who often require high-dose glucocorticoids, this case report highlights the importance of considering opportunistic infections such as nocardiosis, even during the early phase of treatment and without additional immunosuppressive agents. In this paper, we report a case of brain abscess caused by N. farcinica in a patient receiving glucocorticoid therapy for GCA.

Case Report

A 73-year-old man initially presented with a low-grade fever and pain in the neck and in the upper and lower limbs. There was no jaw claudication, tenderness, or cord-like thickening of the temporal artery. PMR was initially suspected, and given the frequent association between PMR and GCA, PET-CT was performed. PET-CT revealed hyperfixation in both femoral and subclavian arteries, the left temporal artery, shoulder joints, sacroiliac joints, and interspinous ligament. The patient’s neck pain was attributed to vasculitis involving the subclavian artery. Based on these findings, and further supported by the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria [9], a diagnosis of GCA associated with PMR was established. Treatment was initiated with oral prednisolone (60 mg/day). As the patient responded well to glucocorticoid therapy, TCZ was not added as adjunctive treatment. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was initiated with sulfamethoxazole-trimethoprim (SMX-TMP). However, due to the development of mild thrombocytopenia, the agent was switched to atovaquone. The prednisolone dose was gradually tapered to 30 mg/day over 2 months, after which the patient was discharged. Over the next 6 weeks, the prednisolone dose was further tapered to 22.5 mg/day. Four months after the initial diagnosis, a follow-up PET-CT scan revealed resolution of the previously observed vascular hyperfixation but detected a new pulmonary nodule in the upper lobe of the left lung, suspicious for malignancy (Figure 1). The past medical history was notable for dyslipidemia and constipation. His regular medications included prednisolone (22.5 mg/day), atovaquone (1500 mg/day), esomeprazole (10 mg/day), and magnesium oxide (330 mg/day). Alfacalcidol (0.5 μg/day) and alendronate sodium (35 mg/week) were prescribed for the prevention of glucocorticoid-induced osteoporosis.

Two weeks after the PET-CT, before we had reviewed its findings, the patient lost consciousness for a few minutes and was admitted to our emergency department at night. Upon admission, the Glasgow Coma Scale was 15, with a heart rate of 101 beats per minute, blood pressure 155/96 mmHg, oxygen saturation 99% on room air, body temperature 36.8°C, respiratory rate 17 breaths per minute, and no symptoms on physical examination. Blood tests in the emergency department showed a white blood cell count of 11 800/μL (reference range: 3900–9700/μL), hemoglobin 13.0 g/dL (13.4–17.1 g/dL), platelet count 212 000/μL (153 000–346 000/μL), aspartate aminotransferase 72 IU/L (5–37 IU/L), alanine aminotransferase 135 IU/L (6–43 IU/L), creatine kinase 43 IU/L (57–240 IU/L), total protein 5.5 g/dL (6.5–8.5 g/dL), albumin 3.1 g/dL (4.0–5.2 g/dL), creatinine 0.59 mg/dL (0.60–1.0 mg/dL), C-reactive protein 0.57 mg/dL (0–0.29 mg/dL), and beta-D-glucan 4.4 pg/mL (0–20 pg/mL). Contrast-enhanced magnetic resonance imaging (MRI) of the head revealed lesions in the left cerebellar lobe (12×10 mm), left temporal lobe (15×11 mm), and left frontal lobe (31×22 mm) (Figure 2). Given the absence of fever, focal neurological deficits, or a marked inflammatory response, these findings were initially suspected to represent brain metastases from lung cancer.

The patient was admitted to the Pulmonology Department for further evaluation. Upon re-evaluation, the MRI findings were considered to be more consistent with brain abscesses. The differential diagnoses for the brain abscesses and a pulmonary nodule included metastatic bacterial infections (such as Staphylococcus aureus), fungal infections (notably Aspergillus or Cryptococcus spp.), tuberculosis, and malignancy. Empiric antibiotic therapy with meropenem (6 g/day) and vancomycin (2 g/day) was initiated on hospital day 2. As the pulmonary nodule and brain lesions were presumed to share a common etiology, bronchoscopy was deferred, and aspiration of the brain abscess was prioritized. On hospital day 4, neurosurgical aspiration of the left frontal lesion was performed (Figure 3). The Gram stain of the aspirated sample revealed gram-positive rods, which were subsequently cultured on AccuRate™ separated Sheep Blood Agar/Chocolate Agar EXII (Shimadzu Diagnostics Co., Japan) at 35°C for 72 hours. The isolate was identified as N. farcinica using matrix-assisted laser desorption ionization mass spectrometry with MBT Compass 4.1 by Microflex LT/SH (Bruker Daltonics, Germany). The minimum inhibitory concentrations (MICs) of the isolate were determined using the broth microdilution method, as described by the guidelines of the Clinical and Laboratory Standards Institute (CLSI) M24-A2 (CLSI, 2018) using the Dry Plate (Eiken Chemical Co., Ltd., Tokyo). The MICs of the isolate were >32 μg/mL for ceftriaxone, 32 μg/mL for cefotaxime, 2 μg/mL for minocycline, 4 μg/mL for levofloxacin, 2 μg/mL for moxifloxacin, ≤2 μg/mL for linezolid, ≤4 μg/mL for amikacin, ≤2 μg/mL for imipenem, 8 μg/mL for tobramycin, and ≤9.5/0.5 μg/mL for SMX-TMP (Table 1). The antibiotic susceptibility profile indicated resistance to cephalosporins and levofloxacin, intermediate susceptibility to minocycline and moxifloxacin, and susceptibility to imipenem, amikacin, and SMX-TMP. On day 9, according to the antibiotic sensitivity profile, meropenem (6 g/day) was continued, and vancomycin was replaced with amikacin (700 mg/day). The patient’s clinical condition improved, and a contrast-enhanced brain MRI on day 25 demonstrated a reduction in the size of the brain abscesses. On day 50, the regimen was switched to SMX-TMP (SMX 3,200 mg/TMP 640 mg/day), as the patient had previously experienced only mild thrombocytopenia as an adverse effect of this agent. However, renal dysfunction emerged 1 week later, necessitating discontinuation of SMX-TMP. Therapy was changed to minocycline (200 mg/day) plus moxifloxacin (400 mg/day) on day 58. During hospitalization, prednisolone was tapered biweekly. He was discharged on day 70 with prescriptions for minocycline (200 mg/day), moxifloxacin (400 mg/day), and prednisolone (8 mg/day). Five months later, subsequent chest imaging showed disappearance of the nodule in the left lung upper lobe (Figure 4). Nine months later, follow-up brain MRI revealed no recurrence (Figure 5). After 8 months of dual antibiotic therapy, the electrocardiogram revealed QT prolongation, attributed to moxifloxacin, which was therefore discontinued. Minocycline monotherapy was continued for an additional 4 months. At final follow-up after completion of minocycline therapy, the patient exhibited no neurological sequelae.

Discussion

Nocardia infections are uncommon, and their clinical manifestations are frequently nonspecific. In addition to standard microbiological investigations, specimens should be obtained from the most accessible site. Conventional staining techniques for cutaneous biopsy (hematoxylin-eosin) may fail to demonstrate the presence of the organism [14]. Nocardia spp. also require prolonged incubation for visible colony formation, typically 2–14 days, with at least 48–72 hours before colonies become evident. Their appearance may vary depending on the culture medium and incubation temperature. For example, N. farcinica can be distinguished by its ability to reach mature growth at 45°C within 72 hours, which is faster than N. asteroides [6]. Misinterpretation of clinical findings and delayed diagnosis significantly contribute to the high morbidity and mortality associated with nocardiosis [15–17]. These microbiological characteristics highlight the importance of close communication with the laboratory and the use of extended culture protocols whenever nocardiosis is suspected.

The management of Nocardia brain abscess requires both surgery and antibiotic therapy. Neurosurgical intervention is generally recommended for large abscesses (>2.5 cm) or those producing a mass effect [18]. Whether needle aspiration or excision is preferable remains debated, although some series suggest that excision may be associated with lower recurrence rates [19]. Because Nocardia spp. can disseminate to multiple organs, whole-body imaging should be performed before neurosurgical procedures to identify other possible sites of infection. Medical therapy typically includes 4–8 weeks of intravenous antibiotics, followed by at least 6 months of oral therapy. SMX-TMP is considered the first-line agent, while linezolid, ceftriaxone, cefotaxime, and minocycline are second-line options [20,21]. Minocycline monotherapy requires caution and should be guided by susceptibility testing. Brain abscesses in immunocompetent patients have also been successfully treated with moxifloxacin [22]. In the present case, SMX-TMP was not selected initially due to a previous adverse effect. The patient was treated with intravenous meropenem and amikacin, after which SMX-TMP was introduced with close monitoring. However, this was discontinued because of worsening renal function. Ultimately, the patient was successfully managed with a combination of oral minocycline and moxifloxacin, which was continued after discharge, despite intermediate susceptibility for both agents. This clinical course illustrates the challenges in balancing antimicrobial efficacy with drug tolerance in patients requiring long-term therapy.

We identified 7 previously published case reports of nocardial infections complicating GCA and summarized the site of infection, Nocardia species, the interval from GCA diagnosis to the onset of nocardiosis, and the immunosuppressive therapies administered at the time of infection (Table 2). Among these cases, 3 did not specify the Nocardia species, while 2 involved N. asteroides, 2 N. cyriacigeorgica, and 1 N. farcinica. Infection sites varied, and clinical presentations often mimicked other conditions [23], leading to delayed recognition. In most cases, nocardiosis developed within 4 months of GCA diagnosis, similar to the present case. Most reports also documented the glucocorticoid dose at the time of infection, with patients receiving moderate- to high-dose glucocorticoid monotherapy [24,25]. By contrast, our patient developed nocardiosis while on 22.5 mg/day of prednisolone, which was the lowest dose among the reported cases. Previous studies have identified glucocorticoid therapy as a major risk factor for nocardiosis. Pulmonary nocardiosis has been associated with long-term glucocorticoid use of at least 10 mg/day of prednisolone [26], while in organ transplant recipients, ≥20 mg/day of prednisolone has been reported as a significant risk factor [27]. These findings suggest that even moderate doses of glucocorticoids, particularly in the early phase of treatment, can predispose patients to nocardiosis.

In addition to vigilance for opportunistic infections such as nocardiosis, current recommendations emphasize the importance of prophylaxis against PJP in patients with autoimmune or inflammatory diseases who are receiving prolonged high-dose glucocorticoids, particularly at prednisolone-equivalent doses of ≥20 mg/day for ≥4 weeks, in those with marked lymphopenia, or in combination with other immunosuppressants [28]. SMX-TMP remains the first-line prophylactic agent, with atovaquone as an alternative in cases of intolerance. Furthermore, long-term glucocorticoid therapy warrants preventive measures against osteoporosis. Prophylaxis should be initiated in patients receiving glucocorticoids for ≥3 months at doses equivalent to ≥2.5 mg/day of prednisolone [29]. Preventive strategies include adequate calcium and vitamin D supplementation, with bisphosphonates recommended as the first-line pharmacologic therapy in high-risk patients.

Our case report adds to the limited literature on nocardiosis in patients with GCA and highlights 2 important points. First, nocardiosis can occur even at moderate doses of glucocorticoids, reinforcing the need for vigilance during immunosuppressive therapy. Second, alternative regimens, such as minocycline and moxifloxacin, may be viable options when SMX-TMP is not tolerated, although careful susceptibility testing and close monitoring remain essential.

Conclusions

This case report underscores the importance of early and proactive awareness of infectious in patients with GCA receiving moderate- to high-dose glucocorticoids. Nocardia infection, although rare, should be considered in the differential diagnosis of neurological or pulmonary lesions in the early phase after initiation of glucocorticoid therapy. Delays in diagnosis, often due to the nonspecific presentation and challenging identification in culture, can significantly increase morbidity and mortality. Prompt identification and tailored antimicrobial therapy are essential for improving outcomes in this vulnerable population.