Atypical Streptococcus sinensis infective endocarditis complicated by bacterial meningitis: A case report and literature review

Abstract

Infective endocarditis caused by Streptococcus sinensis complicated by bacterial meningitis is exceedingly rare. We report a case of a middle-aged man who initially presented with ischemic symptoms in both lower limbs. Echocardiography revealed mitral valvular vegetations, and blood cultures confirmed S. sinensis. During antibiotic therapy, the patient developed somnolence, dysarthria, and left-sided weakness. Metagenomic next-generation sequencing of cerebrospinal fluid detected S. sinensis, thereby confirming infective endocarditis complicated by bacterial meningitis. Given the high surgical risk, combination antimicrobial therapy with vancomycin and ceftriaxone was administered. The patient’s consciousness recovered, and inflammatory and cerebrospinal fluid parameters gradually normalized. This case demonstrates that S. sinensis–associated infective endocarditis can occur in patients with immunocompetent status and often involves the mitral valve, with potential intracranial complications. Early identification by blood culture, metagenomic next-generation sequencing, and 16S rRNA sequencing enables precise pathogen diagnosis. Standardized antibiotic therapy and individualized surgical assessment are crucial to optimize outcomes. For patients with neurological complications, multidisciplinary management is essential to improve survival and long-term prognosis.

Introduction

Infective endocarditis (IE) is a potentially life-threatening condition that affects the endocardial surface of the heart and often involves multiple organ systems. ¹ Neurological complications occur in approximately 20%–40% of cases and include stroke, intracerebral hemorrhage, mycotic aneurysm, meningitis, and brain abscess. ² It is important to distinguish between these complications. The majority of these complications are noninfective, involving embolic stroke or intracerebral hemorrhage resulting from microemboli from valvular vegetations. In contrast, only approximately 1%–6% of patients with IE develop true central nervous system (CNS) infection, such as meningitis or brain abscess, which involves pathogen invasion. ³ Among the common causative pathogens, viridans group streptococci (VGS) are predominant. Streptococcus sinensis, a member of the “sinensis group” within the VGS, was first described in Hong Kong in 2002 in association with IE and has since been reported sporadically worldwide. The oral cavity serves as its natural reservoir. The bacterium can enter the bloodstream through mucosal breaches and subsequently adhere to damaged cardiac valves, resulting in IE. ⁴ Although some patients require surgical intervention, neurological complications remain critical determinants of prognosis. Herein, to the best of our knowledge, we report the first case of S. sinensis IE with secondary bacterial meningitis in mainland China. We also review the relevant literature to summarize its clinical characteristics and management strategies, with an aim to provide valuable insights for clinical practice.

Case report

History

The reporting of this study conforms to the Case Report (CARE) guidelines. ⁵ All patient details have been deidentified. Written informed consent for treatment and publication was obtained from the patient. A man in his mid-40s was admitted to the Affiliated Hospital of North Sichuan Medical College, Nanchong, China, in June 2024 with a 3-month history of recurrent bilateral lower limb pain and a 1-day history of sudden cold numbness in the right lower limb. Three months earlier, he had experienced intermittent, tolerable arthralgia involving both lower limbs without an identifiable cause and did not seek attention. One day prior to admission, the patient developed acute skin coolness below the right knee with numbness and pain that lasted approximately 2 h before relief. He reported no notable past medical history, including no history of rheumatic fever or prior valve surgery, and denied intravenous drug use or recent major dental procedures. On admission, his vital signs were as follows: blood pressure, 126/75 mmHg; temperature, 36.6°C; pulse, 95 beats/min; and respiratory rate, 20 breaths/min. He was alert, oriented, and communicative. Both lower limbs exhibited normal skin color and temperature without tenderness. Mild numbness was observed in the right foot. Motor and sensory function in both lower limbs were intact. Dorsalis pedis pulses were palpable bilaterally, whereas the right posterior tibial pulse was not palpable.

Laboratory findings

The laboratory findings were as follows: red blood cell (RBC) count, 4.02 × 10¹²/L; hemoglobin, 109 g/L (reference range: 130–175 g/L); white blood cell (WBC) count, 9.35 × 10⁹/L with 78.00% neutrophils; platelet (PLT) count, 349 × 10⁹/L; erythrocyte sedimentation rate, 60 mm/h (reference range: 0–21 mm/h); high-sensitivity C-reactive protein (whole blood), 48.37 mg/L (reference range: 0–5 mg/L); total protein, 73.6 g/L (reference range: 65–85 g/L); albumin, 44.8 g/L (reference range: 40–55 g/L); prealbumin, 144.3 mg/L (reference range: 150–400 mg/L). These findings indicated a systemic inflammatory response.

Clinical course

A grade 3/6 blowing systolic murmur was audible at the mitral area. Leukocytosis (Figure 1(a)) and elevated C-reactive protein (CRP) (Figure 1(b)) levels persisted after admission. Transthoracic echocardiography (TTE) showed thickened, rough mitral leaflets, particularly the anterior leaflet, with suspected infection. Prolapse of the A2/A3 scallops with moderate eccentric regurgitation was also noted (Figure 2). On 23 June 2024, blood cultures were positive for S. sinensis. The organism was timely and accurately identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). According to the modified Duke criteria, this case met two major criteria: positive blood cultures with a typical pathogen and echocardiographic evidence of endocardial involvement, thereby confirming the diagnosis of IE due to S. sinensis. Initial empirical antimicrobial treatment consisted of 4 g/day intravenous cefoperazone–sulbactam (q12h) along with 2 g/day vancomycin (q12h). On 29 June 2024, cefoperazone–sulbactam was discontinued following consultation with infectious disease specialists and based on susceptibility results.

Figure 1.

(a) White blood cell (WBC) count and differential cell ratios after admission; (b) dynamic changes in serum C-reactive protein (CRP) levels after admission.

Figure 2.

Transthoracic echocardiography findings showing vegetations on the mitral valve with associated regurgitant flow.

On 4 July 2024, he developed slurred speech and mild left upper-limb weakness. On examination, he was consciousness with dysarthria. The right upper-limb strength was Medical Research Council (MRC) grade 5. On 7 July 2024, his condition had worsened, with somnolence, dysarthria, nuchal rigidity (+), possible conjugate gaze to the right, left central facial and lingual paresis, left upper-limb strength MRC 0, left lower limb strength MRC 1, and positive pathologic reflexes on the left. Chest computed tomography with contrast revealed small inflammatory pulmonary nodules and bilateral pleural effusions with compressive atelectasis of the lower lobes. Bedside full abdominal ultrasonography showed no focal lesions in the liver, spleen, pancreas, or kidneys. Noncontrast head computed tomography showed no evidence of intracranial hemorrhage or hemorrhagic transformation. Conventional magnetic resonance imaging sequences did not demonstrate acute hemorrhage, and susceptibility-weighted imaging showed no findings suggestive of cerebral microbleeds. Head and neck computed tomography angiography demonstrated severe stenosis of the right internal carotid artery with segmental occlusion and nonvisualization of the right middle cerebral artery M1 segment, with attenuated distal branches. Brain magnetic resonance imaging revealed multiple acute ischemic lesions in the right centrum semiovale, periventricular region, basal ganglia, hippocampus, and insular cortex, characterized by diffusion restriction on diffusion-weighted imaging and corresponding signal changes on conventional sequences (Figure 3).

Figure 3.

Brain magnetic resonance imaging (MRI) findings (diffusion-weighted imaging, DWI sequence) demonstrating abnormal high-intensity signals in the right cerebral hemisphere. DWI: diffusion-weighted imaging.

The presence of overt meningeal irritation, persistent fever at the time of lumbar puncture, and rapidly progressive focal neurological deterioration strongly supported bacterial meningitis; therefore, lumbar puncture was performed. Cerebrospinal fluid (CSF) analysis demonstrated marked pleocytosis with a predominant neutrophilic response and significantly elevated protein concentration, findings consistent with bacterial meningitis rather than isolated embolic cerebral infarction. On 10 July 2024, metagenomic next-generation sequencing of CSF identified S. sinensis, concordant with the blood culture isolate, thereby providing direct microbiological evidence supporting the diagnosis of meningitis secondary to IE caused by the same pathogen. TTE demonstrated mitral valve vegetations with severe mitral regurgitation, adequately explaining the patient’s clinical manifestations. Transesophageal echocardiography was not performed because of unstable neurological status during the acute phase; therefore, clinical management decisions were based on TTE findings in conjunction with the overall clinical condition, and conservative medical management was selected.

On 11 July 2024, considering recurrent fever and the possibility of inadequate vancomycin CSF exposure with monotherapy, the regimen was adjusted to 2 g/day vancomycin (q12h) combined with 2 g/day ceftriaxone (q12h). On 17 July 2024, contrast-enhanced brain magnetic resonance imaging demonstrated partial enhancement within the acute ischemic lesions in the right centrum semiovale, periventricular region, basal ganglia, hippocampus, and insular cortex, consistent with blood–brain barrier disruption during the acute infarction stage. Magnetic resonance spectroscopy of the right basal ganglia lesion demonstrated a marked reduction in N-acetylaspartate, mildly increased choline, and an elevated choline-to-creatine ratio. The patient remained febrile, and repeat CSF testing continued to show markedly elevated cell counts and protein; therefore, the antimicrobial regimen was continued. Two weeks later, the fever resolved and inflammatory markers improved. On 31 July 2024, CSF leukocyte counts had decreased substantially, and antimicrobial therapy was discontinued.

After 6 weeks of antimicrobial therapy and supportive care, the patient improved significantly: he was alert and articulate, left-sided strength improved (left upper-limb MRC 1 and left lower limb MRC 3), temperature normalized, inflammatory indices decreased, and serial CSF parameters improved. On follow-up cardiology assessment, persistent anterior mitral leaflet prolapse with severe eccentric regurgitation was noted, with no new vegetations observed. Given his residual neurological deficits, cardiac surgery was deferred, and future intervention will be reconsidered based on close monitoring of cardiac function and reduction in perioperative neurologic risk. Following rehabilitation, he was able to ambulate short distances indoors. At the patient’s and family’s request, he was discharged on 20 August 2024.

Microbiological findings

Pre-antibiotic blood cultures grew S. sinensis, which was promptly identified by MALDI-TOF MS. CSF cytology showed a moderate number of neutrophils, with a few lymphocytes and mesothelial cells. Metagenomic next-generation sequencing (mNGS) of CSF detected S. sinensis in both DNA and RNA libraries. DNA sequencing identified 1378 genus-level reads of Streptococcus, including 764 species-specific reads of S. sinensis, accounting for 81.975% relative abundance among microbial reads. The detected reads covered 46,699 base pairs of the reference genome of S. sinensis, corresponding to 2.2721% coverage and an average sequencing depth of 1.035-fold. RNA sequencing identified 47 genus-level reads of Streptococcus, including 18 species-specific reads of S. sinensis, accounting for 0.747% relative abundance, with 998 base pairs covered and an average sequencing depth of 1.05-fold. Antimicrobial susceptibility testing indicated susceptibility to quinupristin/dalfopristin, linezolid, chloramphenicol, penicillin, cefotaxime, vancomycin, and levofloxacin. S. sinensis was isolated from blood in this middle-aged patient with IE and secondary bacterial meningitis; 16S rRNA sequencing was planned but could not be completed because of limited residual specimen.

Discussion

IE is a severe condition in which circulating pathogens adhere to and colonize the endocardium or cardiac valves, leading to local and systemic infection. It often presents insidiously, follows a protracted course, and is associated with diverse complications and considerable mortality. Despite advances in antimicrobial therapy and cardiac surgery, IE mortality remains 15%–30%, particularly among patients with heart failure or neurological complications. ⁶

Among common pathogens, VGS, owing to their ubiquity and moderate virulence, are the primary cause of subacute IE. With the broader use of molecular diagnostics, the previously underrecognized VGS member S. sinensis has been increasingly identified in IE across multiple countries and regions, suggesting that they may represent an underestimated emerging pathogen.

Streptococcus sinensis was first isolated by Woo et al. ⁷ in 2002 from the blood of a patient in Hong Kong with chronic rheumatic heart disease complicated by IE. The species epithet “sinensis” reflects its Chinese origin. Phylogenetically, it shares ancestry with members of the anginosus and mitis groups. ⁴ Using groEL gene analysis, Woo et al. ⁸ demonstrated a close relationship with S. gordonii. Similarly, 16S rRNA sequencing positioned S. sinensis near the anginosus and mitis/sanguinis clades. Subsequently, phylogenomic and MALDI-TOF studies defined a distinct “sinensis group” comprising S. sinensis, S. oligofermentans, and S. cristatus. ⁴ Though its DNA sequence identity with S. gordonii and S. intermedius approximates 96%–97%, S. sinensis remains genetically distinct at the 16S rRNA, groESL, and sodA loci.^9,10

S. sinensis is a Gram-positive, α-hemolytic coccus that forms pairs or chains and resides as a part of the oral flora, particularly within the gingival sulcus and dental calculus. Its pathogenicity involves adhesion to damaged endocardium, biofilm formation, and quorum-sensing regulation of virulence genes. Additionally, it produces hydrogen peroxide and hemolysin-like substances, which results in tissue inflammation. The organism tolerates bile and grows under low-oxygen conditions, reflecting strong environmental adaptability.

Notably, S. sinensis infections occur not only in immunocompromised hosts but also in otherwise healthy individuals. ¹¹ In the present case, an immunocompetent, middle-aged man without known valvular disease or prior surgery, developed IE and bacterial meningitis. Diagnostic challenges arise because S. sinensis grows slowly and may be misidentified as S. mitis or S. anginosus using conventional methods, thereby delaying diagnosis and treatment.

For etiological confirmation, diagnosis was based on blood culture and 16S rRNA sequencing. More recently, MALDI-TOF and mNGS have increased detection rates. Pan et al. ¹² reported that mNGS detected S. sinensis DNA from blood within 24 h and again from intraoperative valve tissue, underscoring the role of molecular diagnostics in culture-negative or complex infections. Wang et al. ¹³ further showed that mNGS positivity in IE can reach 90%, higher than that of blood culture (approximately 55%), and can reveal resistance genes to guide targeted therapy. In our case, the diagnosis was likewise confirmed by molecular methods. The detection of S. sinensis in CSF by mNGS was supported by high relative abundance in DNA sequencing and concordant detection in both DNA and RNA libraries. Although microbial nucleic acids detected in CSF may theoretically originate from circulating DNA or RNA crossing a disrupted blood–brain barrier after ischemic injury, the combined presence of species-specific reads in both libraries, inflammatory CSF profiles with neutrophilic pleocytosis and elevated protein concentration, persistent fever with meningeal irritation, and subsequent clinical improvement after antimicrobial intensification with agents achieving adequate CNS penetration supports active bacterial meningitis.

Using PubMed (MEDLINE), WanFang, and China National Knowledge Infrastructure (CNKI), with keywords including “endocarditis,” “Streptococcus sinensis,” and “bacterial meningitis,” we identified 15 reported cases of S. sinensis IE to date (including the present case). The age of the patients was 8–75 years, with approximately two-thirds being male. Most patients had congenital or acquired valvular disease; the aortic and mitral valves were most frequently involved. Both single- and dual-valve involvement were reported. With accumulating cases, combined aortic–mitral disease is relatively common, implying combined risks of embolization and hemodynamic disturbance. Vegetations were visible on echocardiography in most cases. Approximately half of the cases had an identifiable oral trigger, including dental procedures, chronic periodontitis, or poor oral hygiene, consistent with the organism’s pathogenesis. Most isolates demonstrated susceptibility to β-lactams. Intravenous treatment was typically administered for 4–6 weeks. Approximately two-thirds of patients underwent valve replacement/repair, and overall outcomes were favorable.

Neurological complications are a major driver of adverse outcomes. Neurological involvement in IE is most commonly associated with septic embolic events. In the present case, an initial septic embolic event with subsequent secondary bacterial meningitis cannot be excluded. However, the presence of persistent fever with meningeal irritation, inflammatory CSF findings with neutrophilic pleocytosis and elevated protein concentration, concordant detection of S. sinensis in blood and CSF, and clinical improvement after antimicrobial intensification supports active bacterial meningitis rather than isolated cardioembolic stroke due to noninfectious etiologies such as atrial fibrillation. Among the 15 clinical descriptions, 3 cases had neurological events. Two representative fatal scenarios have been documented: In one case, the patient developed a near-macular retinal artery embolism postoperatively and died of oral anticoagulation-associated intracranial hematoma 3 years later, with no residual infectious lesions at autopsy; ⁴ In another case, the patient declined surgery and ultimately developed acute right-hemispheric cerebral infarction with hemorrhagic transformation, leading to brain herniation. ¹⁴ In that case, left-hemispheric intracerebral hemorrhage could not exclude a mycotic aneurysm rather than hemorrhagic transformation of a new infarct; however, it remained the direct cause of death. ¹⁵ In contrast, our index patient had secondary bacterial meningitis and survived. However, given the very limited number of reported cases and the heterogeneity of neurological complications, no definitive conclusions regarding prognosis can be drawn. Clinical outcomes appear to vary widely depending on the pattern and severity of CNS involvement. Although rare, S. sinensis IE tends to affect young and middle-aged men with preexisting valvular disease, is characterized by a high rate of vegetation formation, and is frequently associated with oral infection as the precipitating factor. Most patients can be cured with active antimicrobial therapy and surgical intervention where indicated; however, neurological complications markedly increase mortality. Intracranial complications and the timing of surgery are pivotal determinants of outcome. Poor outcomes are chiefly linked to intracerebral hemorrhage, brain herniation, and anticoagulation-related intracranial hematoma. Accordingly, clinical management should emphasize serial neuroimaging, judicious anticoagulation, and case-by-case surgical decision making to improve long-term prognosis.

Conclusions

To the best of our knowledge, we report the first case in mainland China of IE caused by S. sinensis complicated by bacterial meningitis, highlighting the pathogen’s insidious presentation and clinical complexity. S. sinensis represents an emerging viridans streptococcal species with distinctive clinical features, including subtle onset, rapid vegetation formation, and potential intracranial involvement. The advent of molecular diagnostics has greatly improved detection and enabled earlier therapeutic intervention. Adherence to guideline-based antimicrobial therapy, optimal surgical timing, and multidisciplinary collaboration can substantially improve prognosis. Our experience further suggests that, in patients with culture-negative or atypical VGS infections, prompt molecular identification should be pursued, surgical candidacy should be individualized, vigilance for neurologic complications is essential, and long-term follow-up with oral hygiene management is recommended to reduce recurrence and disability.