Multiple Intracranial Nocardia brevicatena Abscesses in a Patient with a Previous History of Tuberculosis: A Case Report

Introduction

Nocardia is a gram-positive opportunistic actinomycete. Nocardial infections of the central nervous system are clinically rare, and the multifocal intracranial subtype is even less frequently encountered, with cases predominantly reported in immunocompromised individuals.¹ Insidious onset and atypical clinical manifestations are observed in this disease, and imaging findings are easily misdiagnosed as tuberculosis, fungal abscesses or intracranial tumors, leading to a low early diagnostic rate.² Rapid disease progression, high mortality, prolonged treatment duration and frequent recurrence are documented, which bring considerable challenges to clinical diagnosis and management. In the present case report, one patient with multifocal intracranial nocardiosis is described. The clinical features, diagnostic procedures and therapeutic regimens are analyzed, so as to provide a reference for the clinical management of similar cases.

Case Presentation

A 55-year-old male patient with a history of pulmonary tuberculosis (TB) presented with persistent dizziness, paroxysmal severe throbbing headaches primarily localized to the vertex, and an unsteady gait. On admission, the patient’s axillary body temperature was 36.5 °C, and the temperature remained below 37 °C throughout the entire initial hospital stay. A chest computed tomography (CT) scan revealed interstitial changes in both lungs, as well as multiple infections and partial consolidation of lung tissue. Pathological examination confirmed laryngeal TB. An enhanced magnetic resonance imaging (MRI) scan of the head showed multiple nodules in the bilateral parieto-occipital lobes, basal ganglia, left temporal lobe, and pons (Figure 1). These nodules were accompanied by significant cerebral edema. Small, spherical, peripheral, enhancing nodules were observed with extensive perilesional edema (Figure 1A–C). No thin meningeal enhancement was detected. No Cryptococcus was detected in the cerebrospinal fluid (CSF) using three staining methods. Aerobic bacterial culture of CSF performed for 10 consecutive days yielded negative results, with no bacterial or fungal growth observed.

Figure 1 T1 FLAIR sequence shows a large edematous lesion (A). Images (B and C) (both T1 FLAIR) show multiple abscess lesions. Imaging findings of recurrence after the patient discontinued medication on his own (Images (D–F)). Following the reinstitution of anti-Nocardia therapy, the patient’s symptoms improved significantly, (G–I). On T2 FLAIR sequence (J), the edema is significantly reduced compared to the previous image (A–I). On T1 FLAIR sequences (K and L), the multiple intracranial abscess lesions have disappeared.

Initially, the presence of positive laryngeal TB pathology suggested the possibility of multiple intracranial TB infections. However, TB treatment was ineffective. Subsequent tests were conducted for parasites and fungi. Next-generation sequencing (NGS) of blood and cerebrospinal fluid samples identified Nocardia brevicatena (N. brevicatena) (Figure 2A and B), and the TB Xpert results were negative. This confirmed the presence of multiple intracranial N. brevicatena infections. Meanwhile, we implemented a multidisciplinary team (MDT) consultation approach involving departments including Neurology, Respiratory Medicine, and Clinical Pharmacy. Through this MDT collaboration, we administered symptomatic and supportive treatments to the patient, encompassing dehydration therapy for intracranial hypertension reduction, neuroprotective therapy, nutritional support, targeted analgesia, and maintenance of electrolyte balance. Concurrently, the triple antimicrobial therapy regimen was ultimately determined, consisting of compound sulfamethoxazole tablets (0.96 g, orally twice daily), amikacin sulfate injection (0.6 g, once daily), and imipenem-cilastatin sodium (0.5 g, every 6 hours). Following one week of treatment, the patient’s condition was significantly improved. Upon discharge, the patient independently discontinued the prescribed medication and opted to resume anti-TB treatment. Two months later, the patient’s condition critically deteriorated, characterized by drowsiness, necessitating readmission. On readmission, the patient’s body temperature was 37.2 °C. During the second hospital stay, body temperature exhibited a slightly elevated trend compared with the first admission, with a peak temperature of 38.9 °C documented on the night of September 3, 2024. Concurrently, the patient’s mean heart rate was significantly higher than that recorded at the initial admission, manifesting as a clinical pattern of overall elevated heart rate with relatively low body temperature—defined as temperature–heart rate dissociation, which suggests the possibility of occult shock. An enhanced MRI of the brain revealed multiple nodules located in the bilateral parieto-occipital lobes, basal ganglia, left temporal lobe, and brainstem, accompanied by significant cerebral edema. Compared to the previous imaging, the walls of certain ring-enhanced lesions were thicker, and some lesions had grown larger with an expanded area of surrounding edema (Figure 1D–F). After re-initiating anti-Nocardia therapy——, these symptoms began to subside approximately one week later (Figure 1G–I), and after 45 days of treatment, the patient had achieved sufficient clinical recovery to meet the discharge criteria. Over the subsequent seven-month follow-up, the patient’s clinical symptoms resolved completely, and MRI scans of the brain returned to normal (Figure 1J–L).

Figure 2 Sequence alignment and identity profile of Nocardia brevicatena detected by NGS. Multiple Mapping: reads aligning to ≥2 microbial species, representing conserved genomic regions (not counted as species-specific sequences); Unique Mapping: reads uniquely aligned to N. brevicatena, the core indicator of pathogen presence; Identity: percentage of base-pair matches to the reference genome, approaching 100% in mapped regions, confirming alignment accuracy. (A) Cerebrospinal fluid (CSF) sample. (B) Peripheral blood sample. The markedly higher number of species-specific sequences in CSF suggests a greater likelihood of primary intracranial nocardiosis.

Discussion and Conclusions

Nocardia spp. are opportunistic pathogens mainly causing lung infections,³ but they can also affect the skin, soft tissues, and CNS, with CNS nocardiosis having a 22.8% mortality rate.^4–6 Nocardia farcinica is the most common species, while Nocardia brevicatena is rare,^3,5,7 with few cases reported.⁸ Nocardia brevicatena, part of the N. brevicatena/N. paucivorans complex (including type II drug susceptibility pattern), as one of the six major pathogenic complexes within the genus Nocardia, cannot break down casein, xanthine, tyrosine, or hypoxanthine and only uses trehalose as a carbon source. It is distinguished from N. paucivorans by its ability to utilize isoamyl alcohol and 1,2-propanediol, as confirmed by DNA–DNA hybridization.^9–12 The susceptibility pattern R(resistance)S(susceptibility)SR to gentamicin, tobramycin, amikacin, and erythromycin further differentiates N. brevicatena from other Nocardia species.¹¹

This document presents the first case of multiple intracranial N. brevicatena infection alongside Mycobacterium tuberculosis coinfection, offering potential insights for improving diagnosis and treatment of N. brevicatena infections.

A definitive diagnosis was crucial for this case. Considering the patient’s history of laryngeal and pulmonary tuberculosis, cerebral tuberculoma was a key differential diagnosis. Active tuberculosis was ruled out due to negative acid-fast bacilli results in CSF and sputum cultures. Brain abscess was excluded through bacterial cultures of CSF and blood. Cranial MRI and parasitic antibody tests helped rule out parasitic intracranial infections. Intracranial tumors were preliminarily excluded using tumor marker detection.

The presence of interstitial pneumonia and pulmonary infection, shown as patchy and honeycomb-like opacities in both lungs, required linking to the patient’s long-term dust exposure and pulmonary alveolar proteinosis. Given the patient’s history of tuberculosis, a multifactorial cause is possible. No immunodeficiency disorders or immunosuppressive treatments were found, suggesting that impaired immunity from previous lung injury might be a mechanism for the co-infection.

As an emerging sequencing modality, NGS presents irreplaceable value in the diagnosis of infectious diseases, particularly for the identification of rare, novel, or non-culturable pathogens, thereby providing a more comprehensive and innovative perspective on microbial communities than conventional culture methods.¹³ Compared with conventional culture approaches, NGS exhibits distinct advantages for the diagnosis of nocardiosis in terms of turnaround time, diagnostic accuracy, and the detection of mixed infections.^14–18 Despite its rapid, broad, efficient, and robust detection capabilities,^19–23 the limitations of NGS warrant considerable attention. These limitations include, but are not limited to, potential nucleic acid contamination, sophisticated data interpretation workflows, and challenges in the identification of antimicrobial resistance genes; furthermore, the longstanding conundrum of distinguishing colonizing agents from pathogenic pathogens remains unresolved.^13,24,25

N. brevicatena is an uncommon pathogen that causes brain infections. Early diagnosis is challenging in patients with a history of TB and N. brevicatena brain infection because detecting the pathogen in brain infections is difficult. This can potentially lead to a misdiagnosis of brain TB. NGS of blood and cerebrospinal fluid testing can identify the pathogen, and TB Xpert can help rule out TB infection, aiding in the diagnosis and treatment of N. brevicatena infections.²⁶