Delayed formation and rupture of intracranial aneurysm following Abiotrophia defectiva endocarditis.

Abiotrophia defectiva is a type of Streptococci and is a rare cause of infectious endocarditis. The progression and outcomes of infectious intracranial aneurysms (IIAs) associated with this species are unknown due to a limited number of reported cases. A woman in her 20s with a sudden headache had a subarachnoid haemorrhage on a head CT scan. Cerebral angiography showed an aneurysm on the right middle cerebral artery. She was diagnosed with infectious endocarditis caused by A. defectiva and underwent parent artery occlusion. Despite initiating targeted antibiotic therapy, a new IIA developed and ruptured 14 days postadmission. A second parent artery occlusion was performed on the new IIA. Following 6 weeks of continued antibiotic therapy, she underwent mitral valve repair and was discharged with no neurological symptoms. Endocarditis caused by A. defectiva can lead to the delayed formation of an IIA. Endovascular treatment was effective for repeated ruptured IIAs.

Abiotrophia spp. and Granulicatella spp. Infective Endocarditis: A Contemporary Perspective.

BACKGROUND: Abiotrophia spp. and Granulicatella spp. are Gram-positive cocci, formerly known as nutritionally variant or deficient Streptococcus. Their role as causative agents of infective endocarditis (IE) is numerically uncertain, as well as diagnostic and clinical management of this infection. The aim of our study is to describe the clinical, microbiological, therapeutic, and prognosis of patients with IE caused by these microorganisms in a large microbiology department. METHODS: Retrospective analysis of all the patients with Abiotrophia spp. and Granulicatella spp. IE registered in our centre in the period 2004-2021. RESULTS: Of the 822 IE in the study period, 10 (1.2%) were caused by Abiotrophia spp. (7) or Granulicatella spp. (3). The species involved were A.defectiva (7), G.adiacens (2) and G.elegans (1). Eight patients were male, their mean age was 46 years and four were younger than 21 years. The most frequent comorbidities were congenital heart disease (4; 40%) and the presence of intracardiac prosthetic material (5; 50%). IE occurred on 5 native valves and 5 prosthetic valve or material. Blood cultures were positive in 8/10 patients, within a mean incubation period of 18.07 hours. In the other two patients, a positive 16SPCR from valve or prosthetic material provided the diagnosis. Surgery for IE was performed in seven patients (70%) and in all cases positive 16S rRNA PCR and sequencing from valve or prosthetic material was demonstrated. Valves and/or prosthetic removed material cultures were positive in four patients. Nine patients received ceftriaxone (4 in monotherapy and 5 in combination with other antibiotics). The mean length of treatment was 6 weeks and IE-associated mortality was 20% at one year follow-up. CONCLUSIONS: Abiotrophia spp. or Granulicatella spp. IE were infrequent but not exceptional in our environment and particularly affected patients with congenital heart disease or prosthetic material. Blood cultures and molecular methods allowed the diagnosis. Most of them required surgery and the associated mortality, in spite of a mean age of 46 years, was high.

[Surgery to Triple Valves for Active Infective Endocarditis Caused by Abiotrophia defectiva:Report of a Case].

We experienced a case of infective endocarditis caused by Abiotrophia defectiva in which aortic, mitral, and tricuspid valve surgery was performed. Even if blood cultures are negative, it is important to treat patients with endocarditis considering the possibility that some organisms are difficult to detect via conventional blood culture. Embolism is a complication that should not be overlooked in cases of infective endocarditis, particularly those caused by Abiotrophia defectiva, which tends to cause embolism. As the patient had splenic and cerebral infarction preoperatively, early surgical intervention was performed to prevent further embolisms, and the patient's postoperative course was excellent.

Clinical characteristics and outcome of infective endocarditis due to Abiotrophia and Granulicatella compared to Viridans group streptococci.

OBJECTIVE: To describe the clinical characteristics and outcome of Abiotrophia and Granulicatella infective endocarditis and compare them with Viridans group streptococci infective endocarditis. METHODS: All patients in the International Collaboration on Endocarditis (ICE) - prospective cohort study (PCS) and the ICE-PLUS cohort were included (n = 8112). Data from patients with definitive or possible IE due to Abiotrophia species, Granulicatella species and Viridans group streptococci was analyzed. A propensity score (PS) analysis comparing the ABI/GRA-IE and VGS-IE groups according to a 1:2 ratio was performed. RESULTS: Forty-eight (0.64%) cases of ABI/GRA-IE and 1,292 (17.2%) VGS-IE were included in the analysis. The median age of patients with ABI/GRA-IE was lower than VGS-IE (48.1 years vs. 57.9 years; p = 0.001). Clinical features and the rate of in-hospital surgery was similar between ABI/GRA-IE and VGS-IE (52.1% vs. 45.4%; p = 0.366). Unadjusted in-hospital death was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 8.8%; p = 0.003), and cumulative six-month mortality was lower in ABI/GRA-IE than VGS-IE (2.1% vs. 11.9%; p<0.001). After PS analysis, in-hospital mortality was similar in both groups, but six-month mortality was lower in the ABI/GRA IE group (2.1% vs. 10.4%; p = 0.029). CONCLUSIONS: Patients with ABI/GRA-IE were younger, had similar clinical features and rates of surgery and better prognosis than VGS-IE.

Right-sided Infective Endocarditis with Ventricular Free Wall Vegetation Caused by Abiotrophia defectiva in a Patient with Unrepaired Ventricular Septal Defect.

To our knowledge, there have been no reports of right-sided infective endocarditis (RSIE) with ventricular free wall vegetation caused by Abiotrophia defectiva. We herein report a case of RSIE caused by A. defectiva with ventricular free wall vegetation in a 27-year-old man with ventricular septal defect (VSD). Computed tomography showed multiple bilateral pulmonary nodular shadows. Transesophageal echocardiography (TEE) demonstrated right ventricular free wall vegetation at the jet stream. Blood culture revealed A. defectiva. These findings are consistent with a diagnosis of infective endocarditis and septic pulmonary embolism. Treatment with ceftriaxone and gentamicin and subsequent surgical VSD closure improved the patient's condition without recurrence.

Contemporary experience of Abiotrophia, Granulicatella and Gemella bacteremia.

BACKGROUND: Abiotrophia, Granulicatella, and Gemella are gastrointestinal microbiota, gram-positive cocci that behave like viridans group streptococci. Despite the low incidence of bacteremia from these organisms, they can lead to infective endocarditis (IE) and other clinical syndromes. Due to scant data, we aim to describe detailed clinical features, management, and outcomes of patients with bacteremia from these organisms. METHODS: We reviewed all adult patients who developed Abiotrophia, Granulicatella, or Gemella bacteremia from 2011 to 2020, at Mayo Clinic. RESULTS: We identified 238 patients with positive blood culture for these organisms. Of those, 161 (67.6%) patients were deemed to have bacteremia of clinical significance; 62 (38.5%) were neutropenic, - none of whom were diagnosed with IE. The primary source of bacteremia for the neutropenic group was the gastrointestinal tract. Among 161 patients, echocardiography was obtained in 88 (54.7%) patients, especially those with unknown sources of bacteremia. A total of 19 cases had IE: 5 (26.3%) Abiotrophia, 11 (57.9%) Granulicatella, and 3 (15.8%) Gemella. Based on known IE scoring systems, the negative predictive value at established cutoffs for these scores, performed with our cohort were 95.9%, 100% and 97.9% for NOVA, HANDOC and DENOVA scores, respectively. We also found that the penicillin-non-susceptible rate was high in Abiotrophia (66.7%) and Granulicatella (53.7%). CONCLUSIONS: We described unique characteristics of Abiotrophia, Granulicatella, and Gemella bacteremia at our institution. Clinical significance, clinical syndrome, their proclivity of endocarditis, and susceptibility pattern should be thoroughly reviewed when encountering these organisms.

CASE REPORT OF ABIOTROPHIA DEFECTIVA ENDOPHTHALMITIS AFTER REPEATED INJECTIONS OF DEXAMETHASONE INTRAVITREAL IMPLANT (OZURDEX).

PURPOSE: To present a case of endophthalmitis caused by Abiotrophia defectiva after repeated injections of dexamethasone intravitreal implant (Ozurdex), in a patient already on systemic immunosuppressive therapy, and discuss the management of this challenging situation. METHODS: Case report and review of literature. RESULTS: A 70-year-old female patient with history of idiopathic pulmonary fibrosis presented for urgent evaluation due to left eye vision loss and mild discomfort 12 days after receiving her seventh dexamethasone implant injection. Ocular history was pertinent for recurrent macular edema resulting from a remote branch vein occlusion. Twelve days after her last injection, visual acuity decreased from 20/30 to counting fingers at 5 feet. Slit-lamp examination showed anterior chamber cell without fibrinoid membranes or hypopyon. Within hours, the patient's clinical appearance progressed. A vitreous tap followed by intravitreal injection of vancomycin (1 mg/0.1 mL) and ceftazidime (2.25 mg/0.1 mL) was performed. The culture from the vitreous sample revealed heavy growth of A. defectiva. Owing to limited improvement, patient was taken to the operating room, and the presence of a full-thickness scleral defect at the site of most recent dexamethasone implant injection was confirmed. Vitrectomy with removal of implant, closure of all sclerotomies, including nonhealing full-thickness scleral defect, and repeated intravitreal antibiotic injection were performed. At the 3-month follow-up, no inflammation was observed, but visual acuity remained poor. CONCLUSION: Intravitreal dexamethasone implant-associated endophthalmitis in the setting of systemic immunosuppression is a rare and challenging situation. Both local and systemic immunosuppression may delay wound healing, predisposing to wound leakage and consequent endophthalmitis. Despite repeated intravitreal antimicrobial injection and vitrectomy with implant removal, A. defectiva endophthalmitis carried a poor visual outcome.

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.

An infrequent etiology of Infective Endocarditis.

Abiotrophia. defectiva is an infrequent but an important cause of infectious endocarditis (IE). IE caused by A. defectiva may actually be more common than what is reported in the literature because of its failure to grown on routine media like blood agar and MacConkey agar, besides difficulty in its identification by conventional methods. IE by A. defectiva generally have more fulminant course and is associated with higher mortality and morbidity due to frequent embolic episodes and valvular tissue destruction. Ceftriaxone or vancomycin in combination with gentamicin and surgical replacement of valve is the recommended management.

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.

Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis.

Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.

Trends in Endophthalmitis Associated With Intravitreal Injection of Anti-VEGF Agentsat a Tertiary Referral Center.

BACKGROUND AND OBJECTIVE: To report the incidence and clinical features of infectious endophthalmitis after intravitreal (IV) injection of anti-vascular endothelial growth factor inhibitors (VEGF) between 2018 and 2020 and to compare to prior rates. PATIENTS AND METHODS: Retrospective analysis of patients with endophthalmitis after anti-VEGF IV injections treated at Bascom Palmer Eye Institute between January 1, 2018, and December 31, 2020. RESULTS: Between 2018 and 2020, the rate of clinically diagnosed endophthalmitis was 0.014% (10/71,858) and of culture-positive was 0.008% (6/71,858). Clinically diagnosed endophthalmitis rates per injection were: aflibercept (0.022%); ranibizumab (0.019%); bevacizumab (0%); and brolucizumab (0%). Clinically diagnosed endophthalmitis rates were similar in the present study compared to those from 2005 to 2017 (P = .84). Fifteen eyes were diagnosed with endophthalmitis (10 in-house, five external referrals). Of culture-positive eyes, the organisms were coagulase-negative Staphylococcus (8/11), Streptococcus species (2/11), and Abiotrophia defectiva (1/11). A universal face-masking policy in 2020 did not lower infection rates (P = .73). CONCLUSION: Endophthalmitis rates after IV anti-VEGF remain low and are similar to prior reports. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:319-326.].

Infective endocarditis by a rare and fastidious agent: Abiotrophia defectiva.

Abiotrophia defectiva is a nutritional variant streptococcus, with affinity for endovascular structures that cannot be cultured on non-supplemented media, leading to a delay in diagnosis. This case describes a 36-year-old woman with a previously known bicuspid aortic valve that presented with asthenia, myalgias and anorexia with 2-month onset. On admission, we documented fever and a systolic murmur. Transthoracic echocardiography revealed an oscillating mass attached to the aortic valve. The patient was admitted with a possible diagnosis of infective endocarditis. Later, blood cultures were positive for A. defectiva Due to severe aortic regurgitation and congestive heart failure, she underwent surgical aortic valve replacement. After 6 weeks of antimicrobial therapy, the patient experienced full recovery. Despite of its rarity, A. defectiva endocarditis is associated with significant morbidity with mortality and physicians must have a high level of suspicion to ensure a prompt diagnosis and provide the appropriate treatment.

A recurrent lung abscess caused by delayed diagnosis of unique co-infection with Abiotrophia defectiva.

We report the case of a lung abscess due to Prevotella baroniae with a co-infection by Abiotrophia defective, which is a 'nutritionally variant streptococci' (NVS), in a 48-year-old patient. The delayed diagnosis of this co-infection led to multiple failures of medical treatment and need for surgery. Pathogenicity of these bacteria is well known, particularly in endocarditis, but not in lung infection. In pulmonary abscesses, co-infection with NVS is difficult to detect. It may explain some medical treatment failures. This case highlights the importance to systematically search for and consider NVS in such clinical contexts.

Simultaneous bilateral revision total knee arthroplasty following Abiotrophia defectiva infection.

A 65-year old man presented with 6-week history of bilateral knee pain and swelling, with difficulty mobilising. He had bilateral total knee arthroplasties in situ performed 5 years prior complicated by postoperative wound infection. Bilateral synovial fluid cultures were positive for Abiotrophia defectiva, and extensive investigations had not identified an extra-articular source of infection. Failing debridement antibiotic and implant retention procedure, the patient underwent a simultaneous bilateral 2-stage revision with articulated cement spacers impregnated with vancomycin and gentamycin. The patient received 6 weeks of intravenous antibiotics after each stage. A. defectiva is a nutritiously fastidious organism, posing a challenge for clinical laboratories to isolate and perform antimicrobial susceptibility testing, yet prosthetic joint infections caused by A. defectiva are scarce in literature and present atypically with subacute signs of chronic infection. This poses a diagnostic and therapeutic challenge, and two-stage revision is the only documented treatment that successfully eradicates the infection.

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.