A rare case of multiple brain abscesses caused by Nocardia abscessus co-infection with tuberculous meningitis in an immunocompetent patient

Abstract

Background

Nocardial brain abscesses are extremely rare and predominantly affect immunocompromised patients, exhibiting a high overall mortality rate. Tuberculosis infections, although they can occur in immunocompetent individuals, are more prevalent in those with compromised immune systems. Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, is associated with a high fatality rate. Co-infection with both pathogens is unusual. To our knowledge, this is the first reported case of multiple brain abscesses caused by Nocardia abscessus (N. abscessus) in a young immunocompetent patient, complicated by tuberculous meningitis.

Case presentation

A 34-year-old male patient initially presented with a week-long history of headaches, predominantly localized in the bilateral frontal region. Additionally, the patient experienced fever, and due to the recurrence of these symptoms, he was admitted to the hospital. Chest computed tomography (CT) scans revealed bilateral pneumonia, and brain magnetic resonance imaging (MRI) strongly suggested the presence of multiple brain abscesses accompanied by meningitis. On the fourth day of hospitalization, the patient’s condition deteriorated, becoming lethargic with severe headaches. His body temperature spiked to 39.5 °C, and signs of elevated intracranial pressure emerged. Subsequently, he underwent neuro-navigation-assisted resection of deep lesions, ventriculostomy for external drainage, and drainage of abscesses. The next day, cerebrospinal fluid (CSF) Xpert MTB/RIF testing yielded positive results for multiple probes and the Mycobacterium tuberculosis (MTB) complex. Pus cultures and sequencing further confirmed an N. abscessus infection. Consequently, the patient was diagnosed with multiple brain abscesses caused by N. abscessus, complicated by tuberculous meningitis. We administered TMP-SMX, imipenem-cilastatin, and intravenous linezolid for the management of nocardial brain abscesses infections, while continuing decompressive ventricular drainage. For empiric treatment of tuberculous meningitis, the patient was started on isoniazid 600 mg/day via intravenous injection, rifampicin 600 mg/day orally, pyrazinamide 1500 mg/day (divided into three oral doses), ethambutol 750 mg/day orally, and dexamethasone at an initial dose of 0.4 mg/kg/day, with a planned gradual reduction starting one week later. Despite 10 days of treatment, the patient showed no significant clinical improvement in the infection, and hydrocephalus worsened. On the 16th day of admission, emergency external ventricular drain placement was performed, and intrathecal amikacin was administered to combat the nocardial brain abscesses. Unfortunately, by the 39th day of admission, the patient’s infection continued to progress, eventually succumbing to septic shock and resulting in death.

Conclusions

Nocardial brain abscesses are associated with a high mortality rate, especially among immunocompromised patients and those with multiple abscesses. Prompt diagnosis, aggressive surgical intervention, and sensitive antibiotic treatment offer the best prospects for curing nocardiosis. Tuberculous meningitis, the most lethal manifestation of Mycobacterium tuberculosis infection, often leads to severe outcomes primarily due to delayed diagnosis and treatment. The GeneXpert/RIF assay, an emerging diagnostic tool, provides a more sensitive and rapid means of detecting TBM. For patients with a high clinical suspicion of TBM, empirical anti-tuberculosis treatment should be initiated immediately. Timely and accurate management, coupled with continuous monitoring of the patient’s condition, is crucial for achieving a favorable prognosis.

Clinical trial number

Not applicable.

Background

Nocardia species are aerobic, Gram - positive bacteria that exhibit modified acid-fast staining positivity and are commonly isolated from soil. Literature reports suggest that these bacteria can cause primary skin diseases in immunocompetent individuals, primary sternal osteomyelitis, and brain abscesses in immunocompromised patients [1]. Nocardial brain abscesses are extremely rare, constituting merely 2% of all intracranial abscesses [2], yet the overall mortality rate can surpass 20% [1]. Infections generally occur via inhalation, and central nervous system (CNS) involvement may result from haematogenous dissemination or directly from adjacent infected cranial sites following head trauma [3, 4].

Tuberculous infections can affect immunocompetent individuals, but they are more prevalent in those with compromised immune systems. TBM, the most severe form of tuberculosis, is characterized by a high mortality rate [5]. Owing to the limitations of various available diagnostic platforms, the global burden of TBM is substantially underestimated [5]. Co-infections with both Nocardia and Mycobacterium tuberculosis are rare. The infrequency of such co-infections may lead to a decreased suspicion of the presence of other pathogens when one pathogen is identified [6]. Notably, the risk of co-infection with Nocardia and Mycobacterium tuberculosis is relatively higher and deserves significant attention. Currently, only a few rare cases of pulmonary co-infection with Nocardia and Mycobacterium tuberculosis have been reported [6, 7]. To the best of our knowledge, this is the first reported case of multiple brain abscesses caused by N. abscessus in a young immunocompetent patient, with the complication of tuberculous meningitis.

Case presentation

A 34-year-old male patient presented with headaches that had begun over a week prior, without any obvious precipitating factors. The pain, predominantly located in the bilateral frontal region, was described as a needle-like sensation, persisting for several hours before spontaneously resolving, and was accompanied by fever and drowsiness. Upon admission to the People’s Hospital of Guangxi Zhuang Autonomous Region, the patient exhibited fever, headache, somnolence, malaise, and speech delay, symptoms that had recurred over the previous week. The patient was unemployed and resided in a county-level municipality. There was no past medical history of hypertension, heart disease, diabetes, or infectious diseases such as hepatitis or tuberculosis. He also denied a history of alcohol or drug abuse.

During the physical examination, the patient was cooperative. Both pupils were equal and round, with a diameter of 3.5 mm, and the light response was sluggish. The body temperature measured 38.3 °C, and blood pressure was 146/92 mmHg. Initial laboratory tests upon admission revealed a white blood cell count (WBC) of 21.83 × 10^9/L (normal range: 3.5–9.5 × 10^9/L), a neutrophil ratio of 94.0%, a C-reactive protein (CRP) level of 86.43 mg/L (normal range: 0–5 mg/L), and a procalcitonin (PCT) level of 0.86 ng/ml (normal range: 0–0.05 ng/mL). Given the patient’s fever and elevated inflammatory markers (WBC, CRP, PCT) at presentation, empirical antibiotic therapy with cefoperazone-sulbactam was initiated.

On the third day of admission, chest CT scans revealed multiple areas of patchy infiltrates, consistent with bilateral pneumonia (Fig. 1). Brain MRI showed multiple cystic lesions in the left thalamus, left parietal lobe, and corpus callosum, with additional similar lesions involving the cortex and subcortical regions of the right temporal lobe. The largest lesion, located in the left parietal lobe, measured 23 × 33 × 15 mm. MRI with and without contrast demonstrated heterogeneous signal characteristics: the cyst wall demonstrates slightly hyperintense signal on T1-weighted imaging (T1WI) and hypointense signal on T2-weighted imaging (T2WI); the cystic fluid exhibits hypointense signal on T1WI and hyperintense signal on T2WI and fluid-attenuated inversion recovery (FLAIR) sequences. Diffusion weighted imaging (DWI) reveals marked hyperintensity within the cystic fluid, corresponding to markedly hypointense signal on apparent diffusion coefficient (ADC) maps. Extensive perilesional edema is noted. Contrast-enhanced imaging demonstrates ring-like enhancement of the lesions, with interconnected cyst cavities. Some cyst walls show uniform thickness with smooth inner and outer margins (Fig. 2.1). On the MRI of the base of the skull, there is obvious linear enhancement on the surface of the brainstem at the base of the skull, involving the bilateral vestibulocochlear nerve bundles, suggesting basal skull meningitis (Fig. 2.2). These findings are strongly suggestive of an infectious etiology, most likely multiple cerebral abscesses with meningitis. Treatment commenced with vancomycin and meropenem for bacterial infection, alongside measures to maintain fluid and electrolyte balance, using mannitol and hypertonic saline to reduce intracranial pressure, as well as analgesics and sedatives.

On the fourth day after admission, the patient continued to experience fever, with a maximum temperature of 39.5 °C, accompanied by severe headache, vomiting, optic disc edema, and lethargy. A neurosurgical procedure was performed to excise the deep-seated supratentorial lesions, conduct ventricular puncture for external drainage, and aspirate the abscesses. Samples of pus and CSF were collected for bacterial and fungal smears, bacterial and fungal cultures, Xpert MTB/RIF testing, and pus sample sequencing.

On the fifth day, the Xpert MTB/RIF test of the ventricular CSF was positive for multiple probes (A, B, C, D, and E), indicating the presence of the Mycobacterium tuberculosis complex. The cerebrospinal fluid adenosine deaminase (ADA) level was elevated to 14.0 U/L (normal range: 0–8 U/L), lactate dehydrogenase (LDH) was elevated to 509 U/L (normal range: 0–40 U/L), total protein was significantly elevated to 9040.5 mg/L (normal range: 150–450 mg/L), and glucose was reduced to 2.28 mmol/L (normal range: 2.5–4.4 mmol/L). The serum glucose level was 5.6 mmol/L (normal range: 3.9–6.1 mmol/L). Gram staining of the pus revealed slender, branching Gram-positive rods arranged in bead-like filamentous structures (Fig. 3A), consistent with Nocardia. Modified acid-fast staining showed acid-fast, thin, branching bacteria, further increasing the suspicion of a Nocardia infection (Fig. 3B). After 48 h of culture, small, dry, wrinkled white colonies appeared on blood agar (Fig. 3C), which were further identified as N. abscessus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Next-generation sequencing of the purulent fluid also confirmed an N. abscessus infection. The patient was diagnosed with multiple brain abscesses caused by N. abscessus, complicated by tuberculous meningitis. We administered TMP-SMX, imipenem-cilastatin, and intravenous linezolid for the management of nocardial brain abscesses infections, while continuing decompressive ventricular drainage. For empiric treatment of tuberculous meningitis, the patient was started on isoniazid 600 mg/day, administered intravenously; rifampicin 600 mg/day, orally; pyrazinamide 1500 mg/day (divided into three oral doses); ethambutol 750 mg/day, orally; and dexamethasone with an initial dose of 0.4 mg/kg/day, with the dose gradually reduced starting one week later. However, after 10 days of this treatment regimen, there was no significant clinical improvement in the infection, and hydrocephalus worsened. On the 16th day after admission, the patient underwent emergency external ventricular drain placement and received intrathecal amikacin for the treatment of nocardial brain abscesses.

On the 30th day of admission, the patient showed decreased blood pressure and oxygen saturation, suspected to be due to respiratory failure and hemodynamic instability. Immediate interventions included assisted ventilation with a ventilator, intravenous volume resuscitation with hydroxyethyl starch, and the administration of epinephrine, lidocaine, and noradrenaline injection to control blood pressure. Subsequently, the patient was transferred to the intensive care unit for continued management. By the 39th day after admission, the patient’s infection had deteriorated, ultimately resulting in death from septic shock.

Fig. 1

Chest CT scans revealed multiple areas of patchy infiltrates, consistent with bilateral pneumonia (arrow)

Fig. 2.1

Brain MRI demonstrates multiple cystic lesions in the left thalamus, left parietal lobe, and corpus callosum. The largest lesion measures 23 × 33 × 15 mm in the left parietal lobe. MRI with and without contrast demonstrated heterogeneous signal characteristics: A: T1WI reveals slightly hyperintense cyst wall and hypointense cystic fluid; B: T2WI shows hypointense cyst wall and hyperintense cystic fluid; C: FLAIR sequence exhibits hyperintense signal within the cystic fluid; D: DWI demonstrates marked hyperintensity within the cystic fluid; E: ADC map shows markedly hypointense signal within the cystic fluid; F: Contrast-enhanced imaging displays ring-like enhancement of the lesions with interconnected cyst cavities

Fig. 2.2

Basal skull meningitis. A and C are T2-FLAIR plain scan sequences, and B and D are T2-FLAIR enhanced scan sequences. There is obvious linear enhancement on the surface of the brainstem at the base of the skull (red arrow), involving the bilateral vestibulocochlear nerve bundles (yellow arrow)

Fig. 3

A: Gram staining of the pus revealed slender branching Gram-positive rods arranged in bead-like filamentous structures; B: Modified acid-fast staining demonstrated acid-fast thin branching bacterium, heightening suspicion for a Nocardia infection; C: After 48 h of culture, small, dry, wrinkled white colonies appeared on blood agar

Discussion and conclusions

Nocardia infection of the CNS has long been considered a condition predominantly affecting immunocompromised individuals, with corticosteroid use and organ transplantation being the most prevalent risk factors [8, 9]. However, emerging evidence indicates that approximately one-third of cases occur in immunocompetent patients [8, 9]. Focal neurological deficits, headache, fever, and altered mental status are the common clinical manifestations, among which seizures, motor weakness, and cranial nerve involvement frequently present as focal deficits [8]. This underscores the necessity of maintaining a high index of suspicion for Nocardia infection even in immunocompetent patients with focal neurological symptoms.

The clinical manifestations of CNS nocardiosis are contingent upon the infection site, its extent, and the patient’s immune status. Immunocompetent patients often exhibit indolent, isolated brain abscesses as less virulent forms. Typically, the symptoms arise from the local effects of brain granulomas or abscesses, while spinal cord or meningeal involvement is relatively rare [4, 10]. On CT scans or MRIs, nocardial brain abscesses are characterized as encapsulated, ring - enhancing lesions [11], but they must be differentiated from tumors, cystic lesions, or areas of necrosis [12]. Given the nonspecific nature of brain abscess symptoms, such as headache and vomiting due to increased intracranial pressure, and the reported occurrence of seizures in up to 50% of cases [11], a microbiological diagnosis is essential for timely and appropriate antibiotic therapy. In addition to routine aerobic and anaerobic cultures, microbiological examination of abscess pus for fungi and acid - fast bacilli is crucial.

The diagnosis of Nocardia mainly relies on direct microscopic examination and pathogen culture. Gram staining, which typically reveals long, branching Gram - positive bacilli with a beaded filamentous structure, and modified acid - fast staining, which yields positive results, help raise early suspicion of Nocardiosis. However, Nocardia cultures grow slowly, and mixed bacterial infections can lead to false - negative identification. If microscopic examination strongly suggests Nocardia, extending the culture time and using agar medium (where Nocardia can produce abundant aerial mycelium) are recommended [13]. MALDI - TOF MS can accurately identify Nocardia genus and species, while PCR and mNGS offer promising approaches for species - level identification. Although PCR may assist in diagnosing Nocardiosis in immunocompromised patients, interpreting results from respiratory samples is challenging due to the possibility of detecting colonization [14]. Nocardia infections are usually inhalational, primarily causing pulmonary infections, with CNS involvement potentially resulting from haematogenous dissemination or direct extension after head trauma. For suspected nocardial pneumonia, sputum or bronchoalveolar lavage fluid (BALF) should be collected, and brain CT or MRI should be performed if intracranial involvement is suspected.

Drug susceptibility patterns vary significantly among Nocardia species [15, 16]. Thus, species - level identification and susceptibility testing are vital for appropriate treatment. In the absence of species identification or when there are delays, empirical treatment is necessary. TMP-SMX remains highly effective against Nocardia in vivo and is the first-line treatment in China [16], and amikacin is effective against most Nocardia isolates except the N. transvalensis complex, which is not prevalent in China [16,17,18,19,20,21,22]. Therefore, linezolid and amikacin can be used for empirical treatment in China. Treatment of nocardiosis generally requires combination antibiotic therapy, such as imipenem, amikacin, and TMP-SMX for invasive infections [23]. Studies suggest that imipenem shows good activity against Nocardia, supporting its inclusion in empirical treatment regimens [15]. In China, amoxicillin/clavulanate, minocycline, or doxycycline can also be considered in combination therapies due to their low resistance rates against common Nocardia species [15]. As the efficacy of other antimicrobial drugs against Nocardia is generally low and resistance varies by species, their use should be avoided without species identification or susceptibility testing [15]. TMP-SMX, being lipophilic, can penetrate the cerebrospinal fluid, but it should be combined with another drug with good CNS penetration and high bioavailability for treating Nocardia brain abscesses [24]. The treatment duration also impacts outcomes, with at least 6 months for non-CNS disease and 12 months for CNS involvement recommended to prevent relapse [25].

Patients in numerous studies have received a combination of drug therapy and neurosurgery [2, 4, 9, 26, 27]. Clinical evidence demonstrates that this integrated approach leads to improved outcomes and higher survival rates. Specifically, patients undergoing combined therapy exhibit a survival rate of 93%, significantly surpassing the 78% survival rate of those treated with antibiotic drugs alone. Notably, the highest mortality rate, reaching 36%, was observed in patients who underwent neurosurgery but lacked targeted antimicrobial treatment [9]. For immunocompromised patients or those with multiple abscesses, more aggressive surgical interventions, such as craniotomy and abscess resection, are often necessary to enhance therapeutic efficacy [2]. Nocardial brain abscesses typically present as multiple lesions, and patients with multiple abscesses face a mortality rate twice as high as those with solitary abscesses (66% vs. 33%) [2]. In contrast, for non-immunocompromised patients with isolated lesions, stereotactic aspiration combined with antibiotic therapy may be sufficient [2]. Irrespective of the patient’s immune status, aspiration is recommended for all abscesses larger than 2.5 cm [2]. Research further indicates that the mortality rate for patients undergoing craniotomy is less than half that of patients who only receive aspiration or drainage and is also lower than that of patients receiving non-surgical treatment [2]. This highlights the critical role of appropriate surgical strategies in the management of nocardial brain abscesses, underscoring the importance of a tailored treatment approach based on patient - specific factors.

For tuberculous meningitis, the deadliest form of Mycobacterium tuberculosis infection [28], diagnosis remains a challenge, mainly due to the failure of early detection and treatment. Traditional diagnostic methods, such as acid - fast staining and pathogen culture, are neither sensitive nor rapid, often resulting in diagnosis and treatment delays. The low pathogen abundance in CSF and the requirement for high - standard laboratory equipment contribute to false - negative culture results [28]. Newer methods like Gene Xpert/RIF and mNGS are more sensitive and faster, yet negative results do not rule out TBM [29, 30]. Clinicians often use scoring systems based on clinical manifestations, CSF characteristics, and imaging to distinguish TBM from other CNS infections. TBM typically presents with recurrent fever, and CSF examination shows lymphocytic pleocytosis, elevated protein, and low glucose levels. Imaging may reveal brain parenchymal nodules, which could be infectious lesions or inflammatory granulomas [31]. For patients with a high suspicion of TBM, empirical anti - tuberculous treatment should be initiated promptly, and timely treatment with continuous monitoring is crucial for a good prognosis.

In this case, a 34-year-old immunocompetent male presented with insidious - onset headaches, fever, and drowsiness. Elevated inflammatory markers and characteristic ring - enhancing lesions on cranial MRI initially suggested a CNS infection. Subsequent microbiological tests, including Xpert MTB/RIF and pathogen sequencing, confirmed a diagnosis of N. abscessus brain abscess complicated by TBM. This case highlights that in patients with normal immune function, the combination of headache, fever, and drowsiness should prompt suspicion of Nocardia and Mycobacterium tuberculosis CNS infections. The superiority of the Xpert MTB/RIF test over traditional smear cultures in detecting Mycobacterium tuberculosis emphasizes the importance of molecular biology testing in TBM diagnosis.​.

For nocardial brain abscesses, a multi-modal approach involving prompt diagnosis, aggressive surgical intervention, and targeted antibiotic therapy is essential. In cases where species identification and susceptibility testing are unavailable, empirical treatment based on current guidelines can be life - saving. For TBM, early initiation of empirical anti - tuberculous treatment and continuous monitoring are critical. This case serves as a reminder of the need for heightened awareness and comprehensive diagnostic strategies when dealing with CNS infections, especially in cases with complex co-infections.