Classified based on the location and extent of the lesions, there are four main types of nocardiosis: cutaneous, pulmonary, neurologic, and disseminated. The risk of death from non-disseminated disease is low, and most patients with primary cutaneous nocardiosis can fully recover. The incidence of pulmonary infections can be as high as 80%, while the incidence of patients with disseminated infections ranges from 44% to 85% [2]. Nocardia has a specific affinity for nervous tissue. Central nervous system (CNS) involvement typically occurs as a result of hematogenous dissemination, direct spread from a nearby site of infection, or head trauma. In this case, the patient's infection might be related to an accidental skin injury during farm work. The delayed diagnosis resulted in the bacteria spreading to the mediastinum and CNS while the patient's immune system was still functioning normally.
There are few reports on mediastinal nocardiosis. In cases of pulmonary infection, the clinical presentation lacks specificity, with fever, cough, and sputum being common symptoms. Common signs of CT imaging include lobar consolidations, isolated or multiple nodules, peribronchiolar consolidations or central lobular nodules, and patchy shadows of varying shapes [5]. A retrospective study reviewed 75 cases of pulmonary nocardiosis and found that the most prevalent CT manifestations were solitary or multiple nodules and/or masses (36.0%) in the lungs, consolidation (28.0%), and nodular bronchiectasis (26.7%) [6]. Only 13 patients (17.3%) exhibited mediastinal lymphadenopathy without the formation of large masses and necrosis. In this case, the patient had a predominantly large necrotic mediastinal mass with a few small pulmonary nodules, leading us to suspect a tumor more likely.
The diagnosis of nocardiosis usually depends on a bacterial culture of the infected tissue. The positive rate of sputum culture is about 39.4%, whereas tissue culture has a positivity rate of about 85% to 95%. Therefore, it is recommended to culture multiple clinical samples multiple times [7,8]. Fortunately, the nocardial infection in this case was confirmed by the first tissue culture obtained through an EBUS-TBNA. Despite the pathogenetic evidence, there was still suspicion of a mediastinal tumor combined with nocardial infection, prompting consideration of either recurrent EBUS-TBNA or surgical exploration. Ultimately, a consensus was reached within the MDT, and single-drug antibiotic therapy was initiated.
There are regional differences in the distribution of Nocardia. Nocardia asteroides is predominantly found in Gansu Province in northwestern China[9], Nocardia brasiliensis is predominantly found in Hunan Province in central China[10], and Nocardia neoformans is predominantly found in Hebei Province in northern China[11]. Furthermore, different species of Nocardia may vary in their susceptibility to antibiotics[12]. This emphasizes the importance of species identification for empirically selecting antibiotics. The preferred method for identifying Nocardia species is through sequence analysis of the 16S ribosomal ribonucleic acid (rRNA) gene. However, due to technical limitations at our hospital, we were unable to conduct species identification and drug susceptibility testing for Nocardia in this patient.
The symptoms of nocardial brain abscess are varied and nonspecific. Patients may present with headaches, nausea, vomiting, meningeal irritation, or focal neurologic deficits. Most patients (93%) with cerebral Nocardia infection present with annular enhanced lesions indicative of brain abscesses [13]. However, in some patients, brain abscesses may be misdiagnosed as primary or metastatic tumors prior to biopsy. In this case, the patient refused to rundergo a biopsy or surgery for disseminated disease. Therefore, the MDT team recommended a CSF examination with bacterial culture and mNGS for its safety and fast diagnostic capabilities for intracranial infections[14].
However, the bacterial culture of the patient's CSF was negative, and mNGS showed Epstein-Barr virus (EBV) infection. The absence of Nocardia may be attributed to the low detection rate in the CSF and the fact that the abscess has not ruptured into the ventricle [15]. The EBV infection was considered to be latent or non-pathogenic [16]. Patients with viral encephalitis frequently exhibit multiple or solitary lesions of low or isointense signal in T1WI phase and high signal on the T2WI phases, with inconspicuous enhancement in the early stage, and diffuse, patchy, or gyrus-like enhancement in the later stage, without a mass effect [17]. All of these signs are markedly different from the intracranial imaging in this case. Therefore, the second multidisciplinary discussion concluded that the patient's multiple intracranial lesions were still considered to be disseminated nocardial abscesses despite the absence of intracranial pathogenetic evidence. They recommended a triple antibiotic regimen in accordance with the guidelines [18, 19].
Sulfonamides have remained a cornerstone of first-line treatment for nocardial infections, with a resistance frequency of ≤9% [20]. However, the mortality rate of nocardial brain abscesses is about 50%, significantly higher than the less than 10% of other bacterial brain abscesses [21]. Therefore, combination therapy is recommended for most patients with disseminated infections, while sulfonamides should be administrated for ≥12 months in immunocompromised or intracranially infected patients [22]. In this case, the triple-drug antibiotic therapy resulted in significant relief of CNS symptoms and a sharp decrease in lesions. Therefore, the regimen may be sufficient to treat disseminated nocardial brain abscesses with less toxicity, helping to avoid invasive surgical debridement or drainage.
In conclusion, mediastinal nocardial infections complicating disseminated brain abscesses are rare and present challenges in differentiating them from brain metastases caused by lung cancer. Accurate identification of the pathogen and differentiation by imaging is key to timely diagnosis, while early initiation of multidrug antibiotic therapy is critical.