Epidemiology, clinical characteristics, and outcome of infective endocarditis due to Abiotrophia and Granulicatella in a Tertiary Hospital in China, 2015-2023: a retrospective study.

BACKGROUND: Abiotrophia (ABI) and Granulicatella (GRA) are rare causative pathogens in infective endocarditis (IE). This study aims to describe the epidemiology, clinical characteristics, and outcome of ABI/GRA-IE. The main features of ABI/GRA-IE were compared with Viridans group streptococci (VGS) IE. METHODS: From January 2015 to December 2023, a total of 1531 definite IE in Zhongshan Hospital, Fudan University, Shanghai, China were retrospectively enrolled in this study. Clinical and laboratory data were collected. RESULTS: Forty-five ABI/GRA-IE cases were identified, representing 2.9% of all IE cases in Zhongshan Hospital between 2015 and 2023, compared to 20.1% of VGS-IE. ABI and GRA IE shared similar clinical characteristics. Congenital valvulopathy was reported in 21 (46.7%) ABI/GRA-IE and 85 (28.8%) VGS-IE (P = 0.025). Pulmonary valve was more frequently affected in ABI/GRA-IE (6 [13.3%]) than VGS-IE (7 [2.4%]) (P = 0.002). Congestive heart failure was observed in 30 (66.7%) ABI/GRA-IE and 103 (34.9%) VGS-IE (P < 0.001). Systemic embolization excluding central nervous system (CNS) occurred in 13 (28.9%) ABI/GRA-IE and 39 (13.2%) VGS-IE (P = 0.012). In-hospital mortality was reported as 4.4% in ABI/GRA-IE and 3.7% in VGS-IE (P = 0.854). CONCLUSION: GRA/ABI-IE was approximately one-seventh as prevalent as VGS-IE. Congestive heart failure and systemic embolization (excluding CNS) were more frequent in GRA/ABI-IE compared to VGS-IE. Mortality of ABI/GRA-IE in this study was comparable to that of VGS-IE and lower than previously reported results.

Abiotrophia defectiva DnaK Promotes Fibronectin-Mediated Adherence to HUVECs and Induces a Proinflammatory Response.

Abiotrophia defectiva is a nutritionally variant streptococci that is found in the oral cavity, and it is an etiologic agent of infective endocarditis. We have previously reported the binding activity of A. defectiva to fibronectin and to human umbilical vein endothelial cells (HUVECs). However, the contribution of some adhesion factors on the binding properties has not been well delineated. In this study, we identified DnaK, a chaperon protein, as being one of the binding molecules of A. defectiva to fibronectin. Recombinant DnaK (rDnaK) bound immobilized fibronectin in a concentration-dependent manner, and anti-DnaK antiserum reduced the binding activity of A. defectiva with both fibronectin and HUVECs. Furthermore, DnaK were observed on the cell surfaces via immune-electroscopic analysis with anti-DnaK antiserum. Expression of IL-8, CCL2, ICAM-1, and VCAM-1 was upregulated with the A. defectiva rDnaK treatment in HUVECs. Furthermore, TNF-α secretion of THP-1 macrophages was also upregulated with the rDnaK. We observed these upregulations in rDnaK treated with polymyxin B, but not in the heat-treated rDnaK. The findings show that A. defectiva DnaK functions not only as an adhesin to HUVECs via the binding to fibronectin but also as a proinflammatory agent in the pathogenicity to cause infective endocarditis.

Abiotrophia defectiva as a cause of infective endocarditis with embolic complications in children.

Abiotrophia defectiva is a rare pathogen of infective endocarditis (IE) but is frequently involved in embolic complication and valvular dysfunction. IE caused by A. defectiva in children is poorly studied. This study reports four cases of A. defectiva IE in children and reviews previously reported five pediatric cases of A. defectiva IE. Most of the patients presented with a subacute course, with prolonged fever or atypical symptoms. Eight patients had embolic complications at presentation. All nine children were treated with combination antimicrobial therapy and six of them received surgical intervention. All patients recovered well without relapse. A. defectiva should be considered in children with infective endocarditis, especially in those with atypical presentations. As complications are frequent and more than half of the patients need surgical treatment, prompt diagnosis along with appropriate treatment is necessary.

Abiotrophia defectiva liver abscess in a teenage boy after a supposedly mild blunt abdominal trauma: a case report.

BACKGROUND: A pyogenic liver abscess (PLA) represents a pus-filled cavity within the liver parenchyma caused by the invasion and multiplication of bacteria. The most common offender isolated from the PLA in children is Staphylococcus aureus. Abiotrophia defectiva is a Gram-positive pleomorphic bacterium, commonly found in the oral cavity, intestinal, and genitourinary mucosa as part of the normal microbiota. It has been proven to be an etiological factor in various infections, but rarely in cases of PLA. The case presented here is, to the best of our knowledge, the first pediatric case of PLA caused by A. defectiva. CASE PRESENTATION: A 13-year-old Caucasian boy presented with a two-day history of abdominal pain, fever up to 40 °C, and polyuria. Contrast-enhanced computed tomography (CT) scan revealed a single, multiloculated liver lesion, suggestive of a liver abscess. The boy had sustained a bicycle handlebar injury to his upper abdomen 3 weeks before the symptoms appeared and had been completely asymptomatic until 2 days before admission. He was successfully treated with antibiotic therapy and open surgical drainage. A. defectiva was isolated from the abscess material. Histopathology report described the lesion as a chronic PLA. CONCLUSIONS: A. defectiva is a highly uncommon cause of liver abscess in children. In such cases, various predisposing factors should be considered, including antecedent blunt abdominal trauma.

Abiotrophia defectiva adhere to saliva-coated hydroxyapatite beads via interactions between salivary proline-rich-proteins and bacterial glyceraldehyde-3-phosphate dehydrogenase.

Abiotrophia defectiva is a species of nutritionally variant streptococci that is found in human saliva and dental plaques and that has been associated with infective endocarditis. In our previous study, it was found that A. defectiva could bind specifically to saliva-coated hydroxyapatite beads (SHA). This study identified a cell surface component of A. defectiva that promotes adherence to SHA beads. The binding of A. defectiva to SHA was reduced in the presence of antibodies against human proline-rich protein (PRP); these results suggested that PRP may be a critical component mediating interactions between A. defectiva and the salivary pellicle. Two-dimensional gel electrophoresis of whole A. defectiva cells followed by Far-Western blotting was conducted by probing with synthetic peptides analogous to the binding region of PRP known as PRP-C. The results indicate that an A. defectiva protein of 37 kDa interacts with PRP-C. The results of amino-terminal sequencing of the adhesive A. defectiva protein revealed significant similarity to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Recombinant GAPDH bound to immobilized PRP-C in a dose-dependent manner and binding of A. defectiva to SHA or to PRP was reduced in the presence of anti-GAPDH antiserum. Western blotting or electron immunomicroscopic observations with anti-GAPDH antiserum revealed that this protein was expressed in both cytosolic and cell wall fractions. These results suggest that A. defectiva could specifically bind to PRP via interactions with cell surface GAPDH; the findings suggest a mechanism underlying A. defectiva-mediated adherence to saliva-coated tooth surfaces.

Epidemiology, Clinical Features, and Outcome of Infective Endocarditis due to Abiotrophia Species and Granulicatella Species: Report of 76 Cases, 2000-2015.

Background: Infective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE. Methods: We performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases). Results: ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)-related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23). Conclusions: GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure.

Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis.

Pathogen identification is important for proper diagnosis and optimal treatment of infective endocarditis (IE). Blood and valve cultures are the gold standard for detecting pathogens responsible for IE. However, these tests only detect culturable pathogens, and have low sensitivity, especially in patients previously treated with antibiotics. Culture-negative IE is still a major clinical problem and a diagnostic challenge. Recently, metagenomic analysis using next generation sequencing has been used to detect pathogens directly from clinical samples. However, there are very few reports of the use of metagenomic analysis for pathogen identification in culture-negative IE cases and the usefulness of this new method is unknown. Here, we report a case of successful pathogen detection with metagenomic analysis in a patient of culture-negative IE. The patient underwent valve replacement surgery and received antibiotics for 5 weeks and survived. Using metagenomic analysis of resected vegetation, we detected Abiotrophia defectiva, which is often associated with culture-negative IE due to its fastidious growth. This method may be useful for pathogen identification in future cases of culture-negative IE.

Abiotrophia defectiva Endocarditis Complicated by Stroke and Spinal Osteomyelitis.

A 67-year-old male with coronary artery disease and aortic stenosis after coronary artery bypass graft (CABG) and aortic valve replacement (AVR) presented after a two-day history of dizziness and frequent falls. Initially, he was found to have a subacute infarct of the left temporal lobe, osteomyelitis of the lumbar spine, and an aortic valve vegetation. Further investigations demonstrated gram-positive bacteremia, and, eventually, the causative organism was identified as Abiotrophia defectiva. He was treated with penicillin and gentamicin in the inpatient setting and then discharged with outpatient intravenous (IV) ceftriaxone for the remainder of the four-week antibiotic course. He did not suffer complications after initiating therapy and recovered. We wish to raise awareness of the existence and complications that can result from A. defectiva endocarditis and encourage further research into effective antibiotic treatment. A. defectiva endocarditis may lead to neurological and orthopedic infective sequelae; understanding and awareness of Abiotrophia spp. infections are important to ensure effective treatment of endocarditis.

Secretome analysis and virulence assessment in Abiotrophia defectiva.

Background: Abiotrophia defectiva, although infrequently occurring, is a notable cause of culture-negative infective endocarditis with limited research on its virulence. Associated with oral infections such as dental caries, exploring its secretome may provide insights into virulence mechanisms. Our study aimed to analyze and characterize the secretome of A. defectiva strain CCUG 27639. Methods: Secretome of A. defectiva was prepared from broth cultures and subjected to mass spectrometry and proteomics for protein identification. Inflammatory potential of the secretome was assessed by ELISA. Results: Eighty-four proteins were identified, with diverse subcellular localizations predicted by PSORTb. Notably, 20 were cytoplasmic, 12 cytoplasmic membrane, 5 extracellular, and 9 cell wall-anchored proteins. Bioinformatics tools revealed 54 proteins secreted via the 'Sec' pathway and 8 via a non-classical pathway. Moonlighting functions were found in 23 proteins, with over 20 exhibiting potential virulence properties, including peroxiredoxin and oligopeptide ABC transporter substrate-binding protein. Gene Ontology and KEGG analyses categorized protein sequences in various pathways. STRING analysis revealed functional protein association networks. Cytokine profiling demonstrated significant proinflammatory cytokine release (IL-8, IL-1ß, and CCL5) from human PBMCs. Conclusions: Our study provides a comprehensive understanding of A. defectiva's secretome, laying the foundation for insights into its pathogenicity.

Abiotrophia defectiva Endocarditis: A Case Diagnosed Incidentally Due to Multi-organ Embolism.

Abiotrophia defectiva, often referred to as nutritionally variant streptococci, is generally a benign part of human microflora, primarily found in the oral cavity, digestive tract, and genitourinary system. However, it can have a significant role in infectious endocarditis (IE). We discuss a case involving a 53-year-old male who displayed serious signs indicative of IE. The individual, who had a history of IgA nephropathy, underwent successful surgical and antibiotic intervention. Given the challenge in treating A. defectiva due to its high antibiotic resistance and the tendency for embolic events and treatment failure, a multidimensional approach involving surgical intervention and specific antibiotic therapy resulted in a successful outcome. This case underlines the need for early identification, immediate treatment, and additional research to understand better and manage A. defectiva endocarditis.

Huge, invasive, and destructive Abiotrophia defectiva endocarditis of the aortic valve and the aortic wall: a case report of an emergency but successful Ross-Konno operation in a child.

Background: Abiotrophia defectiva forms Gram-positive cocci, is part of normal oropharyngeal and gastrointestinal flora, and is rarely involved in endocarditis in children population. Its special nutritional requirements and subacute clinical course may delay diagnosis and proper treatment, leading to life-threatening consequences. Case summary: We report a rare case of huge and destructive A. defectiva infective endocarditis (IE) of the aortic valve and the aortic wall in a 3-year-old child, in follow-up after surgical valvuloplasty for congenital aortic stenosis. The child presented at our department with signs of left side hemiplegia. Transthoracic echocardiography showed severe aortic regurgitation due to large vegetation extending to the aortic wall up to the aortic arch. Blood cultures resulted positive for A. defectiva. He was initially treated conservatively with antibiotic therapy. Ten days after admission, because of clinical deterioration, he required intubation and an emergency Ross-Konno operation. Despite the critical conditions and highly risky surgery, the child recovered well and was discharged home 5 weeks after the operation. Discussion: Abiotrophia defectiva IE is rare in children. Since 1995, only 16 cases of A. defectiva IE have been reported in children, including our case. This pathogen has a higher rate of complications when affecting children rather than adult population. Our case demonstrates that conservative strategy with antibiotics is rarely resolutive in the case of IE caused by A. defectiva. Whenever one or more indications for surgery are present, surgical intervention should always be taken into consideration, even if clinical conditions are prohibitive and surgery is at very high risk.

Abiotrophia defectiva endocarditis - Diagnostic and therapeutic challenge: Case report.

Belonging to the normal oral, gastrointestinal, and urogenital flora, Abiotrophia defectiva is responsible for 1-2 % of all infective endocarditis (IE) cases. The manifestation of A.defectiva endocarditis may by atypical, without fever. Difficult to isolate pathogen requires special culture media. A 45-year-old female was admitted due to anemia and progressive weight loss (8 kg in 6 months). She had a history of benign mitral valve (MV) prolapse and non-stenotic bicuspid aortic valve (BAV). In echocardiography, large vegetations on MV and small vegetation on BAV were found. An enriched medium for fastidious pathogens was used. A. defectiva was identified using biochemical analysis with VITEK-2 Compact. In the fourth week of antibiotic therapy, she required urgent MV replacement due to MV regurgitation progression while vegetation on BAV disappeared. Although patient's frailty and underweight caused prolonged postoperative wound healing, she was transferred to rehabilitation in good conditions. No relapse of IE was observed during five-month follow-up.

Association of infective endocarditis caused by Abiotrophia defectiva with mycotic aneurysm formation: A case report and the review of the literature.

A 74-year-old woman with a history of mitral valve prolapse with mitral regurgitation was transferred to our hospital due to infective endocarditis. Blood culture revealed Abiotrophia defectiva which is known as a nutritional variant streptococcus. Transesophageal echocardiography revealed posterior leaflet (P2) prolapse due to rupture of tendon chordae with severe mitral regurgitation and vegetation on posterior leaflet. Magnetic resonance imaging (MRI) revealed multiple infarction lesions in left temporal lobe and parietal lobe and mycotic aneurysm formation of right middle cerebral artery. Because A. defectiva cannot be cultured on non-supplemented media, their prevalence may be underreported. Learning objective: A number of causative microorganisms of infective endocarditis have been identified. Streptococci and staphylococci account for 80 % of cases of infective endocarditis. Abiotrophia defectiva does not grow in ordinary growth media and its prevalence may be underreported. It is important to know A. defectiva causes infective endocarditis with mycotic aneurysm formation.

Abiotrophia defectiva Endocarditis: A Rare Cause with Aggressive Systemic Embolisation and Need of Valve Replacement.

Infective endocarditis (IE) is a well-described infectious disease, one with increased morbidity and mortality being the third or fourth most common life-threatening infection syndrome. Abiotrophia defectiva is a non-motile, catalase negative, gram-positive coccus in a chain, which can be isolated from the oral cavity, intestinal, and genitourinary tracts. IE due to this agent is rare and associated with heart valve destruction, congestive heart failure, and high embolisation rates, these being the major mortality causes. We present a case of IE due to this agent, complicated with a stroke, and splenic and renal infarction, with the need for aortic valve replacement. This article highlights the gaps of knowledge left by the rarity of this disease, which range from its diagnosis to its treatment, and what we need to mitigate such gaps, supported with a case description of a successful treatment of this infection. LEARNING POINTS: Infective endocarditis due to Abiotrophia defectiva has usually an indolent course, but the embolisation potential is very high.The major causes of mortality with this species are congestive heart failure due to valve destruction and the presence of multiple emboli.Surgical intervention rates are high with Abiotrophia defectiva, reaching 50% of cases.

Catheter related atrial thrombus caused by Abiotrophia defectiva: A case series and review of literature.

Catheter related atrial thrombus (CRAT) is a devastating complication associated with tunneled hemodialysis catheter. Abiotrophia defectiva is a rare fastidious pathogen implicated predominantly in culture negative infective endocarditis. Here we report three cases of CRAT in maintenance hemodialysis patients with variable clinical presentation caused by Abiotrophia defectiva. Video assisted thoracoscopic retrieval of atrial thrombus is a novel technique which is scarcely reported in medical literature for surgical management of large atrial thrombus. Our cases were managed by timely administration of antibiotics and anticoagulants followed by surgical retrieval of atrial thrombus with removal of tunneled dialysis catheter. This case series illustrates the importance of prompt diagnosis, appropriate anticoagulation with antibiotics, and mini-invasive surgical removal of atrial thrombus for the management of CRAT.

Abiotrophia defectiva meningitis following ventriculoperitoneal shunt repair: Case report and literature review.

Introduction: Abiotrophia defectiva is an uncommon and potentially severe cause of bacterial meningitis that can be seen in the setting of neurosurgical procedures. We describe here a case of A. defectiva meningitis in a patient with VP shunt revision. Case report: The patient is a 59-year-old female with VP shunt placed several years prior in the setting of normal pressure hydrocephalus. She underwent successful shunt repair following worsening gait abnormalities. On post-operative day 8 she was brought to the emergency room with fevers, photophobia and altered mentation. CSF cultures returned positive for A. defectiva and she was treated with intravenous vancomycin. Due to the presence of retained hardware she was discharged on chronic suppressive therapy with oral amoxicillin. Conclusion: This case illustrates A. defectiva as a cause of bacterial meningitis following neurosurgical intervention. It is important to consider this fastidious organism and tailor antimicrobial therapy appropriately to prevent significant morbidity and mortality. As was the case with our patient, suppressive therapy may be warranted in setting of retained hardware.

Abiotrophia defectiva causing infective endocarditis with brain infarction and subarachnoid hemorrhage: a case report.

Introduction: A rare pathogen of Infective Endocarditis (IE), the Abiotrophia defectiva, has been known to trigger life-threatening complications. The case discussed here is of a teenager with brain infarction and subarachnoid hemorrhage caused by IE due to A. defectiva. Case report: A 15-year-old girl with movement disorders involving the left limbs and intermittent fevers was admitted to the hospital. A head CT scan revealed cerebral infarction in the right basal ganglia and subarachnoid hemorrhage. Moreover, vegetation on the mitral valve were confirmed by echocardiography. The blood cultures were found to be positive for Gram-positive streptococcus and identified by Vitek mass spectrometry as A. defectiva. She was prescribed vancomycin antibacterial therapy and underwent a surgical mitral valve replacement. Conclusion: This case is suggestive of the fact that A. defectiva is a rare but crucial pathogen of IE-associated stroke. Obtaining early blood cultures and using microbial mass spectrometry could help achieve an accurate diagnosis. Moreover, reasonable anti-infective medications and surgical interventions need to be combined to avoid and/or manage severe complications.

Endophthalmitis Caused by Abiotrophia Defectiva after Anterior Vitrectomy in a Child.

Endophthalmitis caused by Abiotrophia defectiva has never before been reported in a child. We report a case of a 12-year-old female with a history of penetrating keratoplasty, followed years later by open globe injury and repair, and subsequent anterior vitrectomy, which resulted in endophthalmitis caused by Abiotrophia defectiva. We review previous cases of endophthalmitis by this organism and argue that its detection will become more common with the use of 16S rDNA PCR and MALDI-TOF mass spectrometry.