Infective Endocarditis Caused by Streptococcus Sinensis in a Patient with Bioprosthetic Aortic Valve: A Case Report and Literature Review

Introduction

Infective endocarditis (IE) is a rare disease that could be encountered during clinical practice, with viridans group Streptococci comprising 17% of causative organisms.¹ Streptococcus sinensis, a species of viridans streptococcus, was reported pathogenic for IE in 2002 for the first time.² Until now, few cases of Streptococcus sinensis IE have been reported in Asia and Europe, with the majority of patients having congenital heart diseases or chronic rheumatic heart diseases.^3,4 To our knowledge, all the reported cases were native valve endocarditis. Here, we reported the first case of prosthetic valve endocarditis caused by Streptococcus sinensis worldwide.

Case Presentation

A 40-year-old Chinese female came to our tertiary hospital with a chief complaint of intermittent fever for 45 days, with detailed timelines before admission shown in Figure 1. Initially, her body temperature ranged from 37 to 38.5 °C during daytime, and she received intravenous cephalosporin. Her temperature returned to normal but went up when she stopped the antibiotics. Chest computed tomography (CT) scans demonstrated inflammation in the right lower lobe. She was diagnosed with a pulmonary infection and received cephalosporins and azithromycin for 2 weeks. Ten days after discontinuing antibiotic therapies, her temperature went up to 38.5 °C. Complete blood counts and repeated chest CT scans revealed no abnormalities. Two sets of blood cultures were both positive for Gram-positive bacteria without further identification. Transthoracic echocardiography (TTE) demonstrated increased transprosthetic valvular peak velocity. She was treated with oral cephalosporin. Four days before admission, she stopped antibiotics and had a high-grade fever of 39.8 °C. Meanwhile, an 8-millimeter erythematous tender lesion appeared on the left ring finger and automatically resolved 3 days later. The patient had no signs or symptoms of weakness or numbness, abdominal pain, or hematuria. Past medical history included bioprosthetic aortic valve replacement due to bicuspid aortic valve 11 years ago, and previous echocardiography showed bioprosthetic valve dysfunction. She underwent a dental filling procedure without prophylactic antibiotics 1 week before the onset of her symptoms. Physical examination showed a temperature of 38.8 °C and a grade 4 holosystolic murmur over the third intercostal space at the left sternal border.

Figure 1 Timelines of body temperature and antibiotic therapies before admission.

On admission, the patient had a leukocyte count of 6.80*10⁹/L with 80.6% neutrophils. Erythrocyte sedimentation rate (ESR) was 27 mm/h, high-sensitivity C-reactive protein (hsCRP) was 38.37 mg/L, and procalcitonin was 0.18 ng/mL. Electrocardiogram and creatine kinase-MB were normal, while high-sensitivity troponin I (hsTnI) was elevated to 13.1 ng/L. Blood metagenomic next-generation sequencing (mNGS) and 2 sets of blood cultures were drawn. High-throughput sequencing was performed using the NextSeq CN500 platform, and details of mNGS are illustrated in Supplementary Methods. Within 24 hours, mNGS reported Streptococcus sinensis with a sequence number of 19 and a relative abundance of 21.84%. Empiric antimicrobial therapy with vancomycin was used. However, the patient had red rashes after intravenous vancomycin, and antibiotics were switched to penicillin G of 12 million units per day in 6 divided doses. Five days later, both sets of blood cultures were positive for gram-positive cocci, and Streptococcus sinensis was identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MALDI Biotyper Microflex LT, Bruker, Germany). Antibiotic sensitivity tests are shown in Table 1. The pathogen was susceptible to penicillin G, and antibiotic therapies were not adjusted. Transthoracic echocardiography showed significant prosthetic aortic valve stenosis with mild regurgitation. Transesophageal echocardiography (TEE) indicated a 3-millimeter vegetation attached to the prosthetic valve, as shown in Figure 2.

Table 1 Antibiotic Sensitivity Tests of Streptococcus Sinensis from Blood Culture

Figure 2 Transthoracic and transesophageal echocardiography of the patient. Notes: Transthoracic parasternal long axis (A) and short axis (B) view of the prosthetic aortic valve. Transesophageal echocardiography on admission (C) and after 6 weeks (D) of antibiotic therapies, with white arrows pointed to the vegetation.

Meeting 2 major (microbiology and imaging) and 3 minor (predisposition, fever, and immunologic phenomenon) 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) Criteria,⁵ the diagnosis of IE was confirmed. Complications were further evaluated. No embolisms were found through brain magnetic resonance imaging (MRI) and abdominal CT scans. As for immunologic phenomena, the patient had susceptible Osler’s node before admission. Urinalysis and rheumatic factor test yielded negative results.

After confirming the diagnosis, an immediate cardiothoracic consultation was acquired. The patient was suggested to undergo surgical valve replacement as soon as possible. However, due to the small size of the vegetation, the patient declined immediate surgery and preferred a “wait-and-see” strategy with antibiotics.

After antibiotic therapies, the patient’s temperature went back to normal (Figure 3). The patient had negative blood cultures after 2 weeks of penicillin G and switched to ceftriaxone 2 g per day for convenience to reduce the number of intravenous infusions. During the third week of hospitalization, the patient had a low-grade fever of 37.5 °C, and multiple tender red papules appeared on the finger, forearm and lower extremity (Figure 4). All the lesions resolved within 3 days, and they were regarded as Osler’s nodes due to tender features despite uncommon locations. Antibiotics were switched to ceftriaxone 2 g per day and amikacin 0.6 g per day for another 2 weeks. After 6 weeks of antibiotic therapies, repeated TEE showed the vegetation was smaller in a narrow base with a length of 5 mm (Figure 2). Due to fluctuations in body temperature and inflammatory markers (Figure 3), antibiotics were switched to teicoplanin 800 mg per day and levofloxacin 750 mg per day for 2 weeks, and meropenem 1 g q6h for another 2 weeks. At last, the patient finally agreed to undergo surgical interventions and underwent an elective mechanical aortic valve replacement 10 weeks after diagnosis. Leaflet perforation was found during the surgical process, and mNGS of valvular tissue reported both Streptococcus sinensis and Streptococcus sanguinis. The surgery was successful, and no complications were reported during follow-ups.

Figure 3 Timelines of daily body temperature, inflammatory markers, and antibiotic therapies after admission.

Figure 4 Tender red papules found during hospitalization. Notes: Tender red papules on the finger (A), forearm (B), and lower extremity (C) are shown with black arrows.

Discussion

In this case, we presented a patient with refractory fever. Intermittent fever responding to antibiotic therapies made infectious diseases top of differential diagnoses, while the previous history of aortic valve replacement and recent dental procedure without prophylactic antibiotics led to the suspicious diagnosis of IE. The use of mNGS facilitated the identification of pathogenic bacteria Streptococcus sinensis, which had seldom been reported as the cause of IE. Timely empiric antibiotics were given, and TEE was performed, demonstrating aortic valve vegetation and confirming the diagnosis of IE. Results from blood cultures with mass spectrometry further confirmed the pathogen and provided antibiotic sensitivity tests that guided the choice of antibiotics. Prompt diagnosis resulted in a good prognosis for this patient. However, the reluctance to undergo early surgery postponed the whole treatment timeline.

Streptococcus sinensis was first reported in 2002 in Hong Kong, isolating from blood cultures of an IE patient and identifying molecular features by 16S ribosomal RNA (rRNA) gene sequencing.² This species belongs to viridans streptococci, speculated to be the ancestor of anginosus and mitis groups of streptococci.⁶ Despite the name, the species has been reported in Hong Kong, mainland China, Thailand, Switzerland, France, the Netherlands, and Britain,^2,3,7–13 demonstrating its global prevalence. Cases have been reported in both Asians and Caucasians, with some having a travel history to Asia.¹² To our knowledge, the pathogen only infected endocardiums without documented infections elsewhere. Similar to other species of the viridans group, a previous study found a prevalence rate of 22% in saliva specimens from healthy volunteers,¹⁴ indicating that the oral cavity served as the natural reservoir for Streptococcus sinensis. Indeed, at least 4 cases, including ours, reported previous dental manipulation before IE,^4,8,12 implying the importance of antibiotic prophylaxis in high-risk patients and procedures.¹⁵

A literature review of IE caused by Streptococcus sinensis is shown in Table 2. A total of 11 cases have been reported, with patient ages ranging from 19 to 63. Most patients had rheumatic heart diseases and congenital heart diseases, including mitral valve prolapse, patent ductus arteriosus, and bicuspid aortic valve. The majority of patients responded to β-lactams and aminoglycosides, and 63.6% underwent surgical interventions. One patient died due to severe comorbidities and refusal of surgery.¹³ All the other patients had favorable outcomes.

Table 2 Literature Review of Reported Infective Endocarditis Cases Caused by Streptococcus Sinensis

For identification of the pathogen, unique phenotypic findings from Agar cultures and biochemical tests first revealed this novel species.² 16S rRNA gene sequencing further proved the species from a molecular level and demonstrated the phylogenetic relationship between Streptococcus sinensis and related species. The following cases confirmed the species by phylogenetic analysis of 16S rRNA and sodA gene.^9,11 In recent years, MALDI-TOF mass spectrometry has facilitated the rapid and cost-saving identification of pathogens with high sensitivity and specificity.^16,17 In our case, apart from mass spectrometry, we used mNGS for pathogen detection, greatly enhancing the diagnostic efficiency.

Specifically, this is the first case of prosthetic valve endocarditis caused by Streptococcus sinensis. For prophylaxis, antibiotics are recommended for prosthetic valve patients undergoing high-risk procedures, especially dental procedures.¹⁸ For diagnosis, TTE might be suboptimal for prosthetic valves, and timely TEE is needed for clear visualization if clinical suspicion of IE is high.¹⁸ At first, the patient chose a conservative treatment strategy, and antibiotic therapy duration was prolonged compared to those with native valve endocarditis who received 4 to 6 weeks of antibiotics. The latest guidelines have recommended oral antibiotic treatments in clinically stable patients.¹⁸ However, this patient had fluctuations in temperature and inflammatory markers, indicating the need for long-term intravenous antibiotics. Surgery indications are different between native and prosthetic valve endocarditis. Surgery is considered the best treatment option for prosthetic valve endocarditis, while its exact timing is full of debate.¹⁹ The patient had uncomplicated late prosthetic valve endocarditis caused by Streptococcus and declined early surgical intervention. However, close follow-ups showed fluctuations in temperature and inflammatory markers, which all pointed to the difficulty of conservative treatments with prosthetic valve endocarditis. Finally, the patient decided to undergo surgery, and an elective surgical replacement led to a good prognosis. Interestingly, mNGS of valvular tissue found both Streptococcus sinensis and Streptococcus sanguinis. It is possible that this patient had a coinfection of these bacteria, and antibiotic therapies might have led to changes in bacteria proportion.

Conclusion

In Conclusion, Streptococcus sinensis is pathogenic for IE, including prosthetic valve endocarditis. Most cases had Asian origins, but several reported European cases raised global concerns. Most patients had rheumatic heart diseases or congenital heart diseases. Antibiotic prophylaxis is important for high-risk procedures. Timely identification of the bacterium, including blood cultures with mass spectrometry and sensitivity tests, 16S rRNA gene sequencing, and mNGS, is crucial for subsequent diagnosis and treatment.