Cerebral Abscess Infected by Nocardia gipuzkoensis

Abstract

Purpose

Nocardia gipuzkoensis is a novel species that solely identified in patients with pulmonary infections by far. Growing evidence showed the excellent performance of metagenomics next-generation sequencing (mNGS) on pathogenic identification, especially for new species. Here, we described the first case of an elderly female patient suddenly suffering from neurological disorders owing to N. gipuzkoensis infection. And linezolid could effectively treat N. gipuzkoensis infection.

Patients and Methods

The results of imaging, laboratory cultures, and mNGS, as well as therapeutic process are shared.

Results

An elderly female patient suddenly suffered from neurological disorders with dysphasia and right limb trembles under no obvious causes. Subsequently, she was diagnosed as intracranial space-occupying lesions by magnetic resonance imaging (MRI). The isolate from brain secretion was further identified as N. gipuzkoensis through mNGS. The targeted therapy with linezolid according to the antimicrobial susceptibility was used to treat cerebral abscess induced by N. gipuzkoensis. During the follow-up, no relapse was observed for the patient after surgery for 104 days.

Conclusion

Cerebral abscess induced by N. gipuzkoensis is rare disorder with high mortality. mNGS has been identified as a promising tool in pathogen diagnosis for timely therapy. Linezolid as one of the antimicrobial drugs could effectively treat N. gipuzkoensis infection and prevent adverse outcomes.

Introduction

The genus of Nocardia is aerobic, Gram-positive, weakly acid-fast, and branching bacilli bacteria that widely distributed in soil, water, and degraded organic material.^1,2 Over recent years, an increasing number of species have been recognized as pathogens causing pulmonary and cutaneous infections through respiratory inhalation and wound, respectively.^3,4 In addition, cerebral abscess caused by Nocardia is infrequent with a worldwide estimated incidence ranging from 0.3 to 1.3 per 100,000 persons per year.⁵ While nocardial cerebral abscess represents more than three times mortality compared with other pathogens,^6,7 and a recent systematic review highlighted 22.8% mortality in all cases with CNS nocardiosis.² Significantly, it is a novel Nocardia species that was identified in a patient with cerebral abscess through metagenomics next-generation sequencing (mNGS). As we all know, the cases infected by N. gipuzkoensis has solely been reported in patients with bronchiectasis.^8,9 We now described a rare case of cerebral abscess infected by N. gipuzkoensis in an elderly female patient. And the process of treatment was also shared (Figure 1).

Figure 1.

Imaging changes documented the alleviation of brain lesions during the timeline of treatment (a) The initial image of brain MRI at external healthcare center, and the section that indicated by red arrow represented intracranial space-occupying lesions. (b) The image of brain MRI before surgery in our hospital, the region that indicated by red arrows suggested further exacerbation of brain lesion. (c) The image of brain MRI in early postoperative, the region that indicated by red arrow documented the removal of cerebral abscess and existence of perilesional edema. (d) The brain CT scan of day 25 after surgery, documented recovered well of brain lesions without a relapse.

Case Description

A 71-year-old female patient was admitted to our hospital. Twenty-five days before the admission, she suddenly presented with neurological symptoms such as dysphasia and right limb trembling with no obvious causes. She was diagnosed as intracranial space-occupying lesions at Pinghu hospital of traditional Chinese medicine through magnetic resonance imaging (MRI) scanning (Figure 1a). Then the patient was discharged and admitted into the first hospital of Jiaxing. The further extending of brain lesions was reflected by the images of brain MRI showing a space-occupying rounded lesion in left parietal and abnormal signal in the right frontal lobe (Figure 1b). Finally, the patient was admitted to our hospital for treatment owing to the unsolved cerebral lesions.

On admission, the patient had no obvious traumas or liquid secretions on brain, ear, or nose. Physical detection showed that normal consciousness state, sensitive to light reflex, soft neck, normal limb muscle strength, and negative for brain nerve system. Meanwhile, the inflammatory in the upper lobe of the left lung was observed. Except it, no obvious positive signs were observed in cardiopulmonary and abdominal examinations. There were no surgical contraindications that suggested by multiple preoperative detection. The leukocyte count was 6×10⁹/L (normal range is 3.5–9.5×10⁹/L), and ultra-sensitive C reaction protein was 9.07 mg/L (normal range is 0–8 mg/L), the percentage of neutropenia was 52.50 (normal range is 40–75%), the concentration of hemoglobin was 124 g/L (normal range is 130–175 g/L), and the packed cell volume was measured at 38.1% (normal range is 40–50%), respectively. A cerebral lesion resection with the excision and drainage of the abscess was carried out for the patient. Then surgical specimens were sent for histopathological examination along with pathology, culture, and mNGS. After that, the injections of vancomycin (1g, q12h) and meropenem (2g, q8h) were used as empirical treatment.

Postoperatively, the decreased hypointense image in left parietal lesion and surrounding loch were observed through MRI that indicating the removal of lesions and the existence of perilesional edema (Figure 1c). Three-days after surgery, the isolate from cerebral abscess exhibited characteristic of Nocardia genus with the appearance of white, rough, dry colonies on Columbia blood agar medium. mNGS further identified it as N. gipuzkoensis with the 99% similarity according to the Sequence Read Archive (SRA) database (Table 1). And the bacteria with branching rods showed weakly acid-fast (Figure 2). In addition, the isolate of Nocardia genus was not detected in the sputum sample from the patient. And the lesions in lung without obvious changes was observed through lung CT. These findings suggested that the cerebral abscess was affected by N. gipuzkoensis, which is independent of lung infection.

Table 1.

Identification of Nocardia Genus in Cerebral Abscess Using mNGS

Genus				Species
Gram’s Staining	Genus Name	Relative Abundance	Sequences	Species Name	Confidence Level	Sequences
G+	Nocardia	99.7%	160,817	Nocardia gipuzkoensis	99%	27,163

Figure 2.

Microbiology detection of N. gipuzkoensis. (a) The traditional culture of cerebral abscess with the pale yellow, rough, and dry colonies on Columbia Blood Agar medium. (b) The characteristic of weakly acid-fast was identified by acid-fast staining.

Antimicrobial drug susceptibility testing showed that the isolate was susceptible to several antibiotics, including amikacin, linezolid, sulfamethoxazole-trimethoprim (SMZ-TMP) and ceftriaxone (Table 2). According to above, the patient originally received meropenem (2.0g q8h) injection for one time, then orally received linezolid (0.6g, q12h) for continual 3 days. The patient decided to discharge home 12 days after surgery, because she recovered well from the treatment and was no longer suffered from neurological symptoms. Then brain computed tomography (CT) 25 days after surgery documented the complete removal of lesions (Figure 1d). Subsequently, linezolid and sodium valproate sustained-release tablets were continually used for 28 days. Neurological disorders and side effects were not observed in the course of her treatment.

Table 2.

Antimicrobial Drug Susceptibility Testing of Nocardia Gipuzkoensis

Num	Antibiotics	MIC for category (μg/mL)10			MIC for Nocardia	Interpretation
		Susceptible	Intermediate	Resistant
1	Meropenem	–	–	–	8	–
2	Amikacin	≤8	–	≥16	0.064	S
3	Linezolid	≤8	–	–	1	S
4	Vancomycin	–	–	–	16	R
5	Sulfamethoxazole-Trimethoprim	≤2/38		≥4/76	0.5/9.5	S
6	Imipenem	≤4	8	≥16	32	R
7	Ceftriaxone	≤8	16–32	≥64	1	S

Abbreviations: MIC, minimum inhibitory concentration; S, susceptible; R, resistance.

Discussion

Nocardia genus contains a great number of rare opportunistic bacteria that mainly causing pulmonary infections.^3,8,11,12 For extra-pulmonary infections, the central nervous system (CNS) is the most frequent site that exhibits headache, seizures, mental status change, aphasia, and hemiparesis in patients.¹³ Nocardial cerebral abscesses account for about 1–2% of all brain abscesses. Reports involved in N. gipuzkoensis infections were solely detected in patients with bronchiectasis, the brain abscesses were all caused by other than N. gipuzkoensis, including N. farcinica, N. asteroides, N. cyriacigeorgica, N. asiatica, and N. beijingensis (Table 3). Herein, as a novel strain, the first case of cerebral abscess infected by N. gipuzkoensis was described in an elderly female who suddenly suffered from neurological disorders without obvious causes.

Table 3.

Summarizes Some Data from the Case Literature of Cerebral Abscess Infected by Nocardia spp. in Patients

Nocardia spp.	Country	Gender	Age	Nocardia spp. Distribution	Other Comorbidities	Author, Year of Study
N. farcinica	USA	Male	55	Cerebral abscess	Pulmonary alveolar proteinosis	Grond, S. et al 202014
	Indian	Female	76	Cerebral abscess	DM (poor-controlled)	Boctor, N. et al 202315
	Northern Ireland	Male	53	Cerebral abscess	COPD, hypertension, chronic hyponatraemia	Holmes, D. et al 201816
	France	Male	68	Cerebral abscess	Multinodular goiter with Graves orbitopathy, steroids treatment	Zayet, S. et al 202017
	China	Male	55	Pulmonary and cerebral abscess	None	Bai, Y. H. et al 202118
N. asteroides	Iran	Male	71	Cerebral abscess	T2DM, 2-month history of subcutaneous abscess of the right shoulder	Rahdar, H. A. et al 202219
	Maroc	Female	60	Cerebral abscess	DM	Bopaka, R. G. et al 201420
N. cyriacigeorgica	Israel	Male	75	Cerebral abscess	Ischemic heart disease, hypertension, chronic kidney disease, dyslipidemia, well-controlled mild asthma, hypothyroidism, locally invasive prostate carcinoma with good systemic control and complete remission under hormonal therapy.	Gabay, S. et al 202221
	Iran	Female	73	Cerebral abscess	DM, chronic foot ulcer	Khorshidi, M. et al 201822
	France	Male	66	Cerebral abscess	None	Courbin, V. et al 202223
N. asiatica	Brazil	Female	40	Cerebral and mediastinal abscesses	HIV infection	de Azevedo, F. K. S. F. et al 201924
	Korea	Male	51	Cerebral abscess	SLE	Jeong, J. H. et al 201725
N. beijingensis	USA	Male	50	Cerebral abscess	HIV/AIDS	Keenan, J. G. et al 201726
	USA	Male	58	Pulmonary and cerebral abscess	None	Alessandra Diioia et al 202127
	Colombia	Male	58	Cerebral abscess	None	Solano-Varela, D. M. et al 201928
N. cerradoensis	France	Female	59	Brain abscess	A renal transplant	Piau, C.et al 201515
N. lillensis	France	Female	37	Brain abscess	A heart transplant	Flateau, C. et al 201329
N. araoensis	Japan	Male	73	Meningitis, ventriculitis and brain abscess	None	Yamamoto, F. et al 201730
N. paucivorans	Japan	Female	52	Cerebellar abscess	DM (well-controlled)	Shimizu, Y. et al 201931
N. mexicana	USA	/	/	Cerebral abscess	Allo-HCT	Majeed, A. et al 201732

Abbreviations: DM, diabetes mellitus; T2DM, type 2 diabetes mellitus; SLE, systemic lupus erythematosus; COPD, chronic obstructive pulmonary disease; Allo-HCT, Allogenic hematopoietic stem cell transplant.

Nocardial cerebral abscess is generally related to immunodeficiency. While infectious cases of Nocardia spp. in immunocompetent individuals have also been observed. A higher risk of nocardial cerebral abscess challenged individuals with immunosuppression owing to diabetes mellitus, malignancy, solid organ transformation, corticosteroid treatment, HIV/AIDS, and autoimmune disease.^{5,14–16,20–22,24–26,28–34} No obvious immunosuppression was seen in the patient we described, the chronic inflammatory owing to aging within patient might partly explain the occurrence of nocardiosis, leading to the immunocompromised status.⁶

In general, the clinical diagnosis of nocardiosis is extremely challenged due to nonspecific and insidious characteristics compared with other bacterial infections. Up to now, culture is still the gold standard for aetiology, it usually takes about 2 to 7 days for the cultures of Nocardia species to be positive. Compared with traditional culture, mNGS was more sensitive and efficient in detecting Nocardia species, showing tremendous application in rapid diagnosis.³⁵ In our case, mNGS identified the pathogen of brain secretion as N. gipuzkoensis to assist targeted treatment in clinical. We believe that mNGS would be a promising tool in clinical practice.

Vancomycin, as the first-line antibiotic, has been suggested as a good therapeutic option for infections.^36,37 Here, the empirical treatment postoperatively with the combination of vancomycin and meropenem was inaccurate according to the antibiotic susceptibility of the strain. In our study, N.gipuzkonesis was susceptible to sulfamethoxazole-trimethoprim (SMX-TMP) and linezolid. Reviewing the literature, more than 98% of Nocardia genus was sensitive to SMX-TMP treatment, then SMX-TMP has become the primary agent for primary skin nocardiosis and nonsevere lung infection.³⁸ Compared with SMX-TMP, a wider antimicrobial spectrum of linezolid was observed in many studies.³⁸ Linezolid showed bacteriostatic activity against almost all G-positive bacteria, especially for Nocardia spp (100%). Besides, the concentrations of cerebrospinal fluid (CSF) in neurosurgical patients who were treated with recommended dose of linezolid were largely exceeded the minimum inhibitory concentration of the isolates, indicating the excellent penetration of linezolid in the CSF.^39,40 It is to keep linezolid for severe cases or brain infection due to its large CNS penetration, it would be an alternative therapy with rare and mild side effects. In our case, we switched to orally linezolid without relapse of neurological symptoms during 104-day follow-up, indicating linezolid could be potential used for empiric treatment of nocardiosis in China.

Limitation

We have reported a case of an elderly female suffering from intracranial lesions that infected by N. gipuzkoensis. However, the mechanisms and contributes of the strain on brain lesions were needed to be further explored in animal studies.

Conclusion

In conclusion, this report described a CNS infection by a new Nocardia species (N. gipuzkoensis) identified by mNGS. Owing to the limited treatment of vancomycin, linezolid could be promising therapy for the treat of N. gipuzkoensis infection.

Data Sharing Statement

The original data of Nocardia gipuzkoensis sequencing has been submitted in GenBank. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJNA981362.

Ethics and Consent

Written informed consent was provided by the patient to have the case details and any accompanying images published. Our report was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Jiaxing University in accordance with the principles stated in the Declaration of Helsinki to publish the case details (Approval NO., 2023-CA-22).

Disclosure

The author declare that the study was conducted in the absence of any commercial or financial relationships that could be considered as potential conflict of interest.