The Role of Platelets in Infective Endocarditis.

Over the last decade, the incidence of infective endocarditis (IE) has increased, with a change in the frequency of causative bacteria. Early evidence has substantially demonstrated the crucial role of bacterial interaction with human platelets, with no clear mechanistic characterization in the pathogenesis of IE. The pathogenesis of endocarditis is so complex and atypical that it is still unclear how and why certain bacterial species will induce the formation of vegetation. In this review, we will analyze the key role of platelets in the physiopathology of endocarditis and in the formation of vegetation, depending on the bacterial species. We provide a comprehensive outline of the involvement of platelets in the host immune response, investigate the latest developments in platelet therapy, and discuss prospective research avenues for solving the mechanistic enigma of bacteria-platelet interaction for preventive and curative medicine.

Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Infective endocarditis: association between origin of causing bacteria and findings during oral infection screening.

BACKGROUND: Oral streptococci represent the causing microorganism for infective endocarditis (IE) in many patients. The impact of oral infections is questioned, and it has been suggested that bacteraemia due to daily routines may play a bigger part in the aetiology of IE. The aim of this study was to examine the association between oral health and infective endocarditis caused by oral bacteria in comparison with bacteria of other origin than the oral cavity. METHODS: A retrospective study was conducted at Haukeland University Hospital from 2006- 2015. All consecutive adult patients admitted to hospital for treatment of IE and subjected to an oral focus screening including orthopantomogram, were included. The clinical, radiological and laboratory characteristics of the patients, collected during oral infectious focus screening, were analysed. Patient survival was calculated using Kaplan-Meier and mortality rates were compared using Cox-regression. RESULTS: A total of 208 patients were included, 77% (n = 161) male patients and 23% (n = 47) female, mean age was 58 years. A total of 67 (32%) had IE caused by viridans streptococci. No statistically significant correlation could be found between signs of oral infection and IE caused by viridans streptococci. The overall mortality at 30 days was 4.3% (95% CI: 1.6-7.0). There was no statistical difference in mortality between IE caused by viridans streptococci or S. aureus (HRR = 1.16, 95% CI: 0.57-2.37, p = 0.680). CONCLUSION: The study indicates that the association between origin of the IE causing bacteria and findings during oral infection screening might be uncertain and may suggest that the benefit of screening and elimination of oral infections in patients admitted with IE might be overestimated. However, the results should be interpreted with caution and further studies are needed before any definite conclusions can be drawn.

Performance assessment of ASTA MicroIDSys, a new matrix assisted laser desorption ionization-time of flight mass spectrometry system, for identification of viridans group streptococci.

The performance of the ASTA MicroIDSys system (ASTA), a new matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, was evaluated for the identification of viridans group streptococci (VGS) and compared with the results obtained with the Bruker Biotyper system (Bruker Daltonics). A total of 106 Streptococcus reference strains belonging to 24 species from the bacterial strain bank was analyzed using the two MALDI-TOF MS systems. Of the 106 reference strains tested, ASTA MicroIDSys and Bruker Biotyper correctly identified 84.9% and 81.1% at the species level, 100% and 97.2% at the group level and 100% and 98.1% at the genus level, respectively. The difference between the two systems was not statistically significant (P = 0.289). Out of 24 species, 13 species were accurately identified to the species level with 100% accurate identification rates with both systems. The accurate identification rates at the species level of ASTA MicroIDSys and Bruker Biotyper were 100% and 87.5% for the S. anginosus group; 78.4% and 73.5% for the S. mitis group; 91.7% and 91.7% for the S. mutans group; and 100% and 100% for the S. salivarius group, respectively. The ASTA MicroIDSys showed an identification performance equivalent to that of the Bruker Biotyper for VGS. Therefore, it would be useful for the identification of VGS strains in clinical microbiology laboratories.

Streptococcus downii sp. nov., isolated from the oral cavity of a teenager with Down syndrome.

A new α-haemolytic streptococcal strain has been isolated from the dental plaque of a teenager with Down syndrome. Genetic and taxonomic analyses place this Streptococcus within the oralis group. It is a Gram-stain-positive, non-motile, non-spore-forming spherical alpha-haemolytic coccus arranged in chains, and it ferments a large number of monosaccharides and disaccharides, as well as polymeric carbohydrates. It differs biochemically from closely related species of Streptococcus due to its production of α-galactosidase, ß-galactosidase and N-acetyl-ß-d-glucosaminidase and by the absence of arginine dihydrolase deiminase and IgA1-protease. It grows in a temperature range of 25 to 40 °C (optimal growth temperature at 37 °C) and in a pH range of 4.5 to 8 (optimal pH at 7.0). A phylogenetic analysis based on its 16S and 23S rRNA gene sequences placed it close to Streptococcus dentisani CECT 7747T. The ANIb and ANIm values were 93.19 and 93.61 %, respectively, both below the accepted threshold to designate it as a new species of bacteria. A phylogenetic tree based on its core genome placed it close to Streptococcus oralis subsp. dentisani strain CECT 7747T with a distance in the expanded core phylogeny of 0.1298. The in silico DNA-DNA hybridization value was 52.2 % with respect to the closest species, S. oralis subsp. dentisani CECT 7747T. Based on these data, a new species of bacteria within the genus Streptococcus, family Streptococcaceae and order Lactobacillales is described, for which the name of Streptococcus downii sp. nov. is proposed (type strain CECT 9732T=CCUG 73139T).

Viridans streptococcus peritonitis in peritoneal dialysis: clinical characteristics and comparison with concurrent polymicrobial infection.

BACKGROUND: The clinical course of Viridans streptococci (VS) peritonitis in patients undergoing peritoneal dialysis (PD) is rarely reported. This study examined the association of clinical factors with VS peritonitis. METHODS: We retrospectively reviewed clinical data from patients with VS peritonitis from March 1990 to February 2016 in a PD center in Taiwan and evaluated clinical profiles and treatment outcomes. RESULTS: A total of 109 episodes of VS peritonitis in 71 patients identified. Among these patients, 57 had mono-VS peritonitis and 14 had concurrent polymicrobial infections. The median time interval from PD initiation to the first VS peritonitis episode was 18 months (range, 0.6-144 months). Among clinical outcomes, most VS peritonitis episodes were completely cured regardless of a history of peritonitis. All episodes with catheter removal occurred in those without a history of recent antibiotic use. CONCLUSION: VS peritonitis in patients undergoing PD typically has favorable treatment outcomes. Antibiotic therapy should be started promptly.

Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci.

The identification of commensal streptococci species is an everlasting problem due to their ability to genetically transform. A new challenge in this respect is the recent description of Streptococcus pseudopneumoniae as a new species, which was distinguished from closely related pathogenic S. pneumoniae and commensal S. mitis by a variety of physiological and molecular biological tests. Forty-one atypical S. pneumoniae isolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the species S. pseudopneumoniae A comparison with the pbp2x sequences from 120 commensal streptococci isolated from different continents revealed that pbp2x is distinct among penicillin-susceptible S. pseudopneumoniae isolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitive S. mitis account for most of the diverse sequence blocks in resistant S. pseudopneumoniae, S. pneumoniae, and S. mitis, and S. infantis and S. oralis sequences were found in S. pneumoniae from Japan. PBP2x genes of the family of mosaic genes related to pbp2x in the S. pneumoniae clone Spain23F-1 were observed in S. oralis and S. infantis as well, confirming its global distribution. Thirty-eight sites were altered within the PBP2x transpeptidase domains of penicillin-resistant strains, excluding another 37 sites present in the reference genes of sensitive strains. Specific mutational patterns were detected depending on the parental sequence blocks, in agreement with distinct mutational pathways during the development of beta-lactam resistance. The majority of the mutations clustered around the active site, whereas others are likely to affect stability or interactions with the C-terminal domain or partner proteins.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

Infective endocarditis in northeastern Thailand.

Despite rigorous diagnostic testing, the cause of infective endocarditis was identified for just 60 (45.5%) of 132 patients admitted to hospitals in Khon Kaen, Thailand, during January 2010-July 2012. Most pathogens identified were Viridans streptococci and zoonotic bacteria species, as found in other resource-limited countries where underlying rheumatic heart disease is common.

Bacteraemia with gram-positive bacteria-when and how do I need to look for endocarditis?

BACKGROUND: Patients with bacteraemia caused by gram-positive bacteria are at risk for infective endocarditis (IE). Because IE needs long antibiotic treatment and sometimes heart valve surgery, it is very important to identify patients with IE. OBJECTIVES: In this narrative review we present and discuss how to determine which investigations to detect IE that are needed in individual patients with gram-positive bacteraemia. SOURCES: Published original studies and previous reviews in English, within the relevant field are used. CONTENT: First, the different qualities of the bacteraemia in relation to IE risk are discussed. The risk for IE in bacteraemia is related to the species of the bacterium but also to monomicrobial bacteraemia and the number of positive cultures. Second, patient-related factors for IE risk in bacteraemia are presented. Next, the risk stratification systems to determine the risk for IE in gram-positive bacteraemia caused by Staphylococcus aureus, viridans streptococci, and Enterococcus faecalis are presented and their use is discussed. In the last part of the review, an account for the different modalities of IE-investigations is given. The main focus is on echocardiography, which is the cornerstone of IE-investigations. Furthermore, 18F-fluorodesoxyglucose positron emission tomography/computed tomography and cardiac computed tomography are presented and their use is also discussed. A brief account for investigations used to identify embolic phenomena in IE is also given. Finally, we present a flowchart suggesting which investigations to perform in relation to IE in patients with gram-positive bacteraemia. IMPLICATIONS: For the individual patient as well as the healthcare system, it is important both to diagnose IE and to decide when to stop looking for IE. This review might be helpful in finding that balance.

Insights into the enigma of oral streptococci in carcinogenesis.

SUMMARYThe genus Streptococcus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus Streptococcus, viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.

Streptococcus Viridans meningitis in an immunocompetent child: A case report.

In bacterial meningitis, the Viridans streptococci group is not considered a prevalent pathogen. In contrast, the S. viridans group may cause endocarditis and fatal infections in immunocompromised children and adults. We report a 5-year-old immunocompetent boy with signs of meningitis. The CSF tested positive for meningitis with streptococcus viridans.

A Rare Occurrence of Opportunistic Infection by Streptococcus mitis Due to Antibiotic-Induced Neutropenia in Prosthetic Joint Infection.

Prosthetic joint infection (PJI) is a devastating complication in arthroplasty surgery. Although the prevalence is less than 2%, its functional and financial implications are significant. Part of its treatment involves the usage of prolonged and high-dose systemic antibiotics. Ironically, this predisposes the patient to unwanted adverse effects caused by the drugs. We report a case of cefazolin-induced neutropenia that led to Streptococcus mitis (S. mitis) bacteraemia in a patient with Staphylococcus aureus PJI. There have been no previous reports on cefazolin-induced neutropenic bacteraemia complicating the treatment of PJI. This case report aims to create awareness among the attending physicians on the possibility of cefazolin-induced neutropenia, which led to bacteraemia from an opportunistic microorganism. The reversal was as simple as cessation of the antibiotic itself. However, if not recognized, it could be fatal.

Thrombus Aspirates From Patients With Acute Ischemic Stroke Are Infiltrated by Viridans Streptococci.

BACKGROUND: Acute ischemic stroke may be due to embolism from ruptured atherosclerotic carotid arteries. DNA of oral bacteria, mainly the viridans streptococci group, has been detected in thrombus aspirates of patients with ischemic stroke as well as in carotid endarterectomy samples. Because viridans streptococci are known to possess thrombogenic properties, we studied whether their presence in thrombus aspirates and in carotid artery specimens can be confirmed using bacterial immunohistochemistry. METHODS AND RESULTS: Thrombus aspirates from 61 patients with ischemic stroke (70.5% men; mean age, 66.8 years) treated with mechanical thrombectomy, as well as carotid endarterectomy samples from 20 symptomatic patients (65.0% men; mean age, 66.2 years) and 48 carotid artery samples from nonstroke autopsy cases (62.5% men; mean age, 66.4 years), were immunostained with an antibody cocktail against 3 species (Streptococcus sanguinis, Streptococcus mitis, and Streptococcus gordonii) of viridans streptococci. Of the thrombus aspirates, 84.8% were immunopositive for viridans streptococci group bacteria, as were 80.0% of the carotid endarterectomy samples, whereas immunopositivity was observed in 31.3% of the carotid artery samples from nonstroke autopsies. Most streptococci were detected inside neutrophil granulocytes, but there were also remnants of bacterial biofilm as well as free bacterial infiltrates in some samples. CONCLUSIONS: Oral streptococci were found in aspirated thrombi of patients with acute ischemic stroke as well as in carotid artery samples. Our results suggest that viridans streptococci group bacteria may play a role in the pathophysiology of ischemic stroke.

Microbial isolates and antibiotic sensitivity in patients hospitalized with odontogenic infections at a tertiary center over 10 years.

Objectives: This study investigated causative strains and their antibiotic sensitivity in patients who were hospitalized for maxillofacial odontogenic infections at a tertiary center in South Korea over the past 10 years with the aim of providing guidelines for the selection of appropriate empirical antibiotics. Materials and Methods: Patients with head and neck fascial space abscesses due to odontogenic infections who underwent incision and drainage surgery with pus culture tests between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery, Dankook University Hospital were included. The bacterial isolates and antibiotic sensitivity of each strain were analyzed for 2013-2022, 2013-2017, and 2018-2022. The affected fascial spaces were classified into primary, secondary, and deep neck spaces. Results: In the 192 patients included in this study, 302 strains were detected. Viridans streptococcus had the highest frequency (51.7%), followed by Prevotella spp. (16.9%), Staphylococcus spp. (5.6%), and Klebsiella pneumoniae (4.6%). The identification rate of viridans streptococcus significantly increased from 41.8% in 2013-2017 to 60.9% in 2018-2022. Viridans streptococcus showed an antibiotic sensitivity of 80.5% to ampicillin; the sensitivity to penicillin antibiotics decreased over the study period. Antibiotic susceptibility was approximately 94% for third-generation cephalosporins. K. pneumoniae, which was identified at a high percentage in patients with deep neck space infection, showed increasing antibiotic resistance to most antibiotics over the study period. Conclusion: Viridans streptococcus was identified in head and neck fascial space abscesses with the highest frequency. Empirical antibiotics should be effective against this strain; penicillin antibiotics are considered inappropriate. For effective treatment of deep neck space abscesses, bacterial culture and antibiotic sensitivity tests performed as soon as possible are essential.

Coronary artery mycotic aneurysm in a patient suffering from subacute endocarditis: a case report and literature review.

Although mycotic aneurysm is a known and important disease in the cerebrovascular system, especially the brain, there are scarce reports about coronary artery mycotic aneurysms (CAMA). CAMA can occur not only in the context of endocarditis but also as a rare adverse event of coronary artery stenting, which has been used more extensively in recent years. Accordingly, it is essential to pay greater attention to its associated presentations and clinical course. Considering the scant evidence available, reporting the disease course of each patient with CAMA can help increase the physician's knowledge about this condition, which is why we are reporting this case. A 42-year-old man with diabetes was referred to our center with embolic left cerebellar infarction 3 months earlier, as well as a 2-month history of feverishness before his referral. His blood culture was positive for Viridans Streptococci, and he had paraclinical signs of inflammation and two- and three-dimensional transthoracic and transesophageal echocardiography (2D & 3D TTE and TEE) signs of aortic and mitral valves' infective endocarditis with the destruction of the aortic valve, severe aortic and mitral regurgitation, severe pulmonary hypertension, and moderate biventricular systolic dysfunction. Regarding the obviously dilated left main coronary artery on TEE images, contrast-enhanced chest multidetector computed tomography was performed for better assessment of coronary arteries with suspicion of CAMA, which confirmed aneurysmal dilatation of the proximal left main coronary artery. The presence of bacteria was confirmed on staining the valvular tissue, resected during the surgical replacement of aortic and mitral valves. As the cardiac surgeon considered CAMA resection and coronary bypass grafting high risk for the patient, he received parenteral antibiotic therapy, for 6 weeks. At 1-year follow-up, he was doing well with no signs/symptoms of endocarditis and well-functioning mechanical prosthetic valves. This case shows the significance of considering CAMA in the setting of endocarditis, resistant to medical and/or surgical therapy or in patients with coronary aneurysm, simultaneous with active endocarditis. Therefore, more attention should be paid to this extravalvular complication of endocarditis, and its possibility should be considered and investigated in any patient presented with valvular endocarditis, especially involving the aortic valve.

A Rare Case of Viridans Group Streptococci Pyogenic Liver Abscess in a Young Male With No Prior Risk Factors.

Pyogenic liver abscesses (PLAs) secondary to bacterial etiologies are rare in North America and other developed countries. The predominant etiology of PLAs is an infection extending from the hepatobiliary or intestinal system. As such, the most common pathogens isolated from PLA in the United States are Escherichia coli and Klebsiella. Viridans group streptococci (VGS), on the other hand, are a large group of commensal bacteria in the oral flora and are a significantly less common cause of infection. Here, we report a rare case of a complicated isolated VGS PLA in a patient without known comorbidities. The patient was born and raised in the United States without recent travel history. Computed tomography (CT) with contrast showed multiple hypodense multiloculated lesions in the right lobe of the liver, measuring up to 13 cm, with mild wall thickening of the distal ileum and cecum. The abscesses were confirmed later as Streptococcus viridans PLA. The patient was treated with CT-guided drainage and IV antibiotics and, after that, made a quick recovery and was discharged. Our case underlines the significance of considering liver abscess as a differential even in previously healthy individuals with no known prior comorbid conditions, as prompt recognition is imperative in preventing morbidity and mortality.

Microbiological Epidemiology of Invasive Infections Due to Non-Beta-Hemolytic Streptococci, France, 2021.

Non-beta-hemolytic streptococci (NBHS), also referred to as viridans streptococci, represent an underestimated cause of human invasive diseases. Their resistance to antibiotics, including beta-lactam agents, often complicate their therapeutic management. A prospective multicenter study was conducted by the French National Reference Center for Streptococci between March and April 2021 to describe the clinical and microbiological epidemiology of invasive infections due to NBHS, excluding pneumococcus. A total of 522 NBHS invasive cases were collected. Distribution among streptococcal groups was: Streptococcus anginosus (33%), Streptococcus mitis (28%), Streptococcus sanguinis (16%), Streptococcus bovis/equinus (15%), Streptococcus salivarius (8%), and Streptococcus mutans (<1%). Median age of infection was 68 years old (range <1 day to 100 years). Cases were more frequent in male patients (gender ratio M/F 2.1:1) and manifested mainly as bacteremia without focus (46%), intra-abdominal infections (18%) and endocarditis (11%). All isolates were susceptible to glycopeptides and displayed low-level inherent gentamicin resistance. All isolates of the S. bovis/equinus, S. anginosus, and S. mutans groups were susceptible to beta-lactams. Conversely, nonsusceptibility to beta-lactams was found in 31%, 28%, and 52% of S. mitis, S. salivarius, and S. sanguinis isolates, respectively. The screening for beta-lactam resistance using the recommended one unit benzylpenicillin disk screening failed to detect 21% of resistant isolates (21/99). Last, overall resistance rates to the alternative anti-streptococcal molecules clindamycin and moxifloxacin were 29% (149/522) and 1.6% (8/505), respectively. IMPORTANCE NBHS are recognized as opportunistic pathogens particularly involved in infections of the elderly and immunocompromised patients. This study underlines their importance as common causes of severe and difficult-to-treat infections such as endocarditis. Although species of the S. anginosus and S. bovis/equinus groups remain constantly susceptible to beta-lams, resistance in oral streptococci exceeds 30% and screening techniques are not fully reliable. Therefore, accurate species identification and antimicrobial susceptibility testing by MICs determination appears essential for the treatment of NBHS invasive infections, together with continued epidemiological surveillance.