Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice.

Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Severely complicated ear infection in a patient treated with ixekizumab: a case report.

We report a case of a severe ear infection in a 35-year-old man treated with ixekizumab for psoriasis. Ixekizumab is a humanized monoclonal antibody that selectively prevents the interaction between interleukin 17 A and its receptor. Biologicals like ixekizumab are used to achieve symptom relief in autoimmune diseases including psoriasis. Unlike the mild upper respiratory tract infections usually described as side-effects of this treatment, we report a case of a patient who presented with a severe otitis media, complicated with a facial paresis and nasopharyngeal abscess. To the best of our knowledge, this is the first case presenting a severe, complicated ear infection as a possible side effect of ixekizumab. We conclude that when using ixekizumab, vigilance for upper airway infections is needed and if necessary, interruption of therapy should be considered. However, further research is needed to confirm this hypothesis.

Studies of Streptococcus anginosus Virulence in Dictyostelium discoideum and Galleria mellonella Models.

For many years, Streptococcus anginosus has been considered a commensal colonizing the oral cavity, as well as the gastrointestinal and genitourinary tracts. However, recent epidemiological and clinical data designate this bacterium as an emerging opportunistic pathogen. Despite the reported pathogenicity of S. anginosus, the molecular mechanism underpinning its virulence is poorly described. Therefore, our goal was to develop and optimize efficient and simple infection models that can be applied to examine the virulence of S. anginosus and to study host-pathogen interactions. Using 23 S. anginosus isolates collected from different infections, including severe and superficial infections, as well as an attenuated strain devoid of CppA, we demonstrate for the first time that Dictyostelium discoideum is a suitable model for initial, fast, and large-scale screening of virulence. Furthermore, we found that another nonvertebrate animal model, Galleria mellonella, can be used to study the pathogenesis of S. anginosus infection, with an emphasis on the interactions between the pathogen and host innate immunity. Examining the profile of immune defense genes, including antimicrobial peptides, opsonins, regulators of nodulation, and inhibitors of proteases, by quantitative PCR (qPCR) we identified different immune response profiles depending on the S. anginosus strain. Using these models, we show that S. anginosus is resistant to the bactericidal activity of phagocytes, a phenomenon confirmed using human neutrophils. Notably, since we found that the data from these models corresponded to the clinical severity of infection, we propose their further application to studies of the virulence of S. anginosus.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Intramedullary spinal cord abscess with brain abscess due to subacute infective endocarditis.

BACKGROUND: Intramedullary spinal cord abscesses (ISCA) are rare, even more so in association with brain abscesses. Infective endocarditis is an uncommon cause of ISCA. In this case study, we report a patient with intramedullary abscesses and multiple brain abscesses due to subacute infective endocarditis. CASE PRESENTATION: A 54-year-old man presented with a 7-day history of head and neck pain and numbness in both lower limbs. Intramedullary abscess combined with multiple brain abscesses was diagnosed based on blood culture, head and spinal magnetic resonance imaging (MRI), contrast-enhanced MRI, and magnetic resonance spectroscopy. Echocardiography revealed vegetations on the mitral valve and severe mitral regurgitation, which the authors believe was caused by subacute infective endocarditis. With ceftriaxone combined with linezolid anti-infective therapy, the patient's symptoms and imaging was improved during follow-up. CONCLUSIONS: This case hopes to raise the vigilance of clinicians for ISCA. When considering a patient with an ISCA, it is necessary to complete blood culture, MRI of the brain and spinal cord, and echocardiography to further identify whether the patient also has a brain abscess and whether the cause is infective endocarditis.

Human serum albumin stabilizes streptolysin S activity secreted in the extracellular milieu by streptolysin S-producing streptococci.

Anginosus group streptococci (AGS) are opportunistic pathogens of the human oral cavity; however, their pathogenicity has not been discussed in detail. Oral streptococci live in the gingival sulcus, from where they can easily translocate into the bloodstream due to periodontal diseases and dental treatment and cause hazardous effects on the host through their virulence factors. Streptolysin S (SLS), a pathogenic factor produced by ß-hemolytic species/strains belonging to AGS, plays an important role in damaging host cells. Therefore, we investigated the SLS-dependent cytotoxicity of ß-hemolytic Streptococcus anginosus subsp. anginosus (SAA), focusing on different growth conditions such as in the bloodstream. Consequently, SLS-dependent hemolytic activity/cytotoxicity in the culture supernatant of ß-hemolytic SAA was stabilized by blood components, particularly human serum albumin (HSA). The present study suggests that the secreted SLS, not only from ß-hemolytic SAA, but also from other SLS-producing streptococci, is stabilized by HSA. As HSA is the most abundant protein in human plasma, the results of this study provide new insights into the risk of SLS-producing streptococci which can translocate into the bloodstream.

Elderly onset atypical Lemierre's syndrome concurrent with a rheumatoid vasculitis sacral ulcer infection: a case report.

BACKGROUND: Typical Lemierre's syndrome is usually secondary to an oropharyngeal infection. Recently, several cases following a primary infection site other than the oropharynx have been reported as atypical Lemierre's syndrome; although, these primary lesions are limited to the head and neck. This is the first case potentially sequential to infectious foci outside the head and neck. CASE PRESENTATION: We describe an atypical Lemierre's syndrome in a 72-year-old woman with rheumatoid arthritis, which occurred during the treatment of Streptococcus anginosus bacteremia acquired from a sacral ulcer infection related to rheumatoid vasculitis. At first, the symptoms resolved after the initial administration of vancomycin for the bacteremia caused by methicillin-resistant Staphylococcus aureus and Streptococcus anginosus that entered via a sacral ulcer. On the 8th day, the patient developed a fever of 40 °C and unexpectedly required 10 L of oxygen due to rapid deterioration of oxygenation temporarily. Immediately contrast-enhanced computed tomography was performed to investigate systemic thrombosis including pulmonary embolism. Afterward, the newly formed thrombi at the right external jugular vein, bilateral internal jugular veins, and the right small saphenous vein were detected, and apixaban was started. On the 9th day, the patient again had an intermittent fever of 39.7 °C, and continuous Streptococcus anginosus bacteremia was revealed; subsequently, clindamycin was administered. On the 10th day, she developed a left hemothorax; consequently, apixaban was discontinued, and a thoracic drain was inserted. She repeatedly had an intermittent fever of 40.3 °C, and contrast-enhanced computed tomography detected an abscess formation at the left parotid gland, pterygoid muscle group, and masseter muscle. After Lemierre's syndrome was diagnosed in combination with the abovementioned jugular vein thrombus, clindamycin was replaced with meropenem, and vancomycin was increased. Swelling of the lower part of the left ear became prominent with delay and peaked at approximately the 16th day. The subsequent treatment course was favorable, and she was discharged on the 41st day. CONCLUSION: Clinicians should consider Lemierre's syndrome as the differential diagnosis of internal jugular vein thrombosis occurring during sepsis, even though an antibiotic is administered or a primary infection site is anything besides the oropharynx.

Lemierre's syndrome complicating deep neck abscess: a case report.

BACKGROUND: Lemierre's Syndrome is a severe medical condition that can result from oropharyngeal infection, typically caused by Fusobacterium necrophorum, leading to sepsis, internal jugular vein thrombosis, and metastatic septic emboli. However, there is limited literature on this syndrome caused by Streptococcus anginosus, and few previous cases have been reported to have deep neck space infection. We present the first case of Lemierre's Syndrome caused by Streptococcus anginosus with deep neck abscess. CASE PRESENTATION: A 53-year-old male patient with no significant medical history presented with right neck pain after accidentally swallowing a fish bone one month ago. Laryngoscopy did not reveal any abnormalities. Five days prior to admission, the patient developed high fever. Imaging studies showed internal jugular vein thrombosis and a neck abscess surrounding the carotid artery sheath. Blood culture results were positive for Streptococcus anginosus infection, and the patient was diagnosed with Lemierre's syndrome. The patient underwent surgical drainage and received antibiotics and anticoagulant therapy, and had satisfactory clinical progress. He was discharged after a 16-day hospitalization. CONCLUSIONS: Although Lemierre's syndrome is rare, it needs attention because it can lead to serious complications and requires timely treatment. Deep neck space infections can be life-threatening and doctors must be aware of its potential severity.

A mixed infection involving Bacteroides denticanum, Lactobacillus salivarius, and Streptococcus anginosus as causative agents of abscess around a pharyngo-esophageal anastomosis and acute vertebral osteomyelitis: Identification by ribosomal RNA sequencing of bacterial isolates.

"Bacteroides denticanum" is an anaerobic, non-spore-forming, gram-negative bacterium with a rod morphology typical of canine, ovine, and macropod oral flora. There is only one report of bloodstream infection caused by "B. denticanum" from a dog bite in human. Here, we report a case with no history of animal contact who developed an abscess caused by "B. denticanum" around a pharyngo-esophageal anastomosis after undergoing balloon dilatation procedure for stenosis following laryngectomy. The patient was a 73-year-old man with laryngeal cancer, esophageal cancer, hyperuricemia, dyslipidemia, and hypertension with a 4-week history of cervical pain, sore throat, and fever. Computed tomography showed fluid collection on the posterior pharyngeal wall. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) identified Bacteroides pyogenes, Lactobacillus salivarius, and Streptococcus anginosus from abscess aspiration. 16S ribosomal RNA sequencing re-identified the Bacteroides species as "B. denticanum". T2-weighted magnetic resonance images showed a high signal intensity adjacent to the anterior vertebral body of C3-C7. The diagnosis was peripharyngeal esophageal anastomotic abscess and acute vertebral osteomyelitis caused by "B. denticanum", L. salivarius, and S. anginosus. The patient was treated with sulbactam ampicillin intravenously for 14 days and then switched to oral amoxicillin with clavulanic acid for 6 weeks. To our knowledge, this is the first report of a human infection caused by "B. denticanum" without a history of animal contact. Despite remarkable advancements facilitated by MALDI-TOF MS in microbiological diagnosis, the accurate identification of novel, emerging, or uncommon microorganisms and comprehending their pathogenicity, suitable therapy, and follow up necessitate sophisticated molecular approaches.

A rare paediatric case of possible infective endocarditis caused by Streptococcus anginosus.

Infective endocarditis in children is a rare but serious condition that requires prompt management. We present a case of an 11-year-old boy with subacute bacterial endocarditis caused by Streptococcus anginosus, an unusual causative microorganism for infective endocarditis. The patient presented with a history of malaise, fatigue, and one subjective tactile fever. To the best of our knowledge, this is the first paediatric case of possible infective endocarditis caused by Streptococcus anginosus.

Polymicrobial Bacterial Meningitis in a Patient with Chronic Suppurative Otitis Media: Case Report and Literature Review.

Polymicrobial meningitis is a rare entity in the adult population, especially in the antibiotic era. However, disorders such as chronic suppurative otitis media (CSOM) or even poor oral hygiene are considered risk factors for the development of such cerebral infection. We report a case of polymicrobial meningitis associated with oto-mastoiditis in a 64-year-old female patient known to have CSOM. The patient presented atypical symptoms for community-acquired meningitis, showing subacute evolution of headache, without fever or neck stiffness. The aerobe microorganisms Streptococcus anginosus and Corynebacterium spp., sensitive to beta-lactamines, and the anaerobe Prevotella spp., resistant to penicillin and metronidazole, were isolated from CSF specimens, while Proteus mirabilis and Enterococcus faecalis were identified from the ear drainage. The diversity of pathogens identified in our case led us to the hypothesis of two different sources of meningitis: otogenic and/or odontogenic. Favorable evolution was obtained after a multi-disciplinary approach, combining surgery and broad-spectrum antibiotics. In addition, we performed a literature review that highlights the low incidence of polymicrobial mixed aerobe-anaerobe meningitis.

Spontaneous intramedullary abscesses caused by Streptococcus anginosus: two case reports and review of the literature.

BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.

Case of infant invasive Streptococcus intermedius infection suggesting the need for anaerobic cultures.

We report the case of an immunocompetent 6-month-old boy with a lung abscess and empyema caused by Streptococcus intermedius detected only from anaerobic cultures. Invasive S. intermedius infection in infants is rare. S. intermedius has been infrequently reported as a causative microorganism of lung abscess and empyema as most of the S. intermedius infections in children have been head and neck infections. While anaerobic cultures are often not performed for infant patients, we suggest the need for these cultures, including blood cultures, especially in cases of pediatric empyema, brain abscess, and liver abscess, which can be caused by S. intermedius.

Predicting bacteremia caused by Streptococcus anginosus group: A new scoring method.

BACKGROUND: Viridans group streptococci (VGS) are the most common causative organisms of infective endocarditis. Among VGS, the Streptococcus anginosus group (SAG) is often associated with abscess formation, and delayed diagnosis leads to increased morbidity and mortality. This study aims to examine the factors associated with SAG bacteremia and develop a predictive scoring method. METHODS: This single-center retrospective case-control study of patients with VGS bacteremia compared the background and clinical characteristics between the SAG and non-SAG groups. The univariate analysis used the χ2 test and t-test. The multivariate analysis was conducted using logistic regression. RESULTS: Out of 161 patients, 95 had SAG and 66 had non-SAG bacteremia. Age >63 years: 2 points (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.64-7.54); solid tumor: 2 points (OR = 4.44, 95% CI: 1.42-6.77); C-reactive protein >7.61 mg/dL: 3 points (OR = 5.40, 95% CI: 2.49-11.72), and white blood cell count >8550/µL: 2 points (OR = 2.76, 95% CI: 1.29-2.91) were found to be independently associated with SAG bacteremia. After totaling the above variables and adding 1 point for diabetes mellitus, the area under the receiver operating curve was 0.81 (95% CI: 0.74-0.88). The sensitivity and specificity were 51% and 88%, respectively, at a cut-off of 6 points. CONCLUSIONS: In patients with VGS bacteremia, a score of 6 points or higher using this method predicts SAG with high specificity.

Disseminated Streptococcus anginosus invasive infection with intracranial subdural abscess formation.

We report the case of a 67-year-old woman with disseminated Streptococcus anginosus invasive infection. Even under a maximal dose of susceptible antibiotics, her condition was complicated by pulmonary septic emboli and intracranial subdural abscess. Effective antibiotics and emergent surgical drainage were performed, but the sequelae of aphasia and hemiplegia remained. Underlying immunocompromised conditions of diabetes mellitus and monoclonal gammopathy of unknown significance might partially affect the clinical course of invasive S. anginosus infection. Once the infection becomes invasive, it can be refractory and difficult to treat. Clinicians should acknowledge the characteristics of invasive S. anginosus infection.

Streptococcus anginosus group infections in hospitalised children and young people.

AIM: The Streptococcus anginosus group (SAG) comprises three bacterial species colonising the mouth and gastrointestinal and genitourinary tracts and capable of serious pyogenic infections. Although well-described in adults, studies in children are limited. Here, we characterise paediatric SAG infections from a single Australian centre. METHODS: Hospitalised patients aged ≤18 years with positive SAG cultures from January 2009 to December 2019 were identified from Pathology Queensland's Gold Coast Laboratory database and their medical records were reviewed. RESULTS: Two-hundred children (62% male), median age 12 years (interquartile range 6-16), with positive SAG cultures were identified. Overall, 90% received intravenous antibiotics, 89% underwent surgical drainage, 23% were readmitted and 15% required additional surgery. The most common sites were the abdomen (39%), soft tissues (36%) and head and neck regions (21%). Since 2011, Pathology Queensland reported SAG at the species level (n = 133). Of these, S. anginosus was the most prevalent (39%), then S. constellatus (34%) and S. intermedius (27%). Compared with the other two species, S. intermedius was most commonly associated with head and neck infections (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.4-3.5), while S. constellatus (RR = 1.7, 95% CI 1.2-2.4) and S. anginosus (RR = 1.5, 95% CI 1.0-2.0) were each associated with a higher risk of intra-abdominal infection than S. intermedius. Since February 2015, the number of children admitted with SAG-associated intra-abdominal infection per 1000 hospitalisations increased by 29% annually compared with an annual decline of 8% in previous years. CONCLUSIONS: SAG infections occur at various anatomical sites. Despite antibiotics and surgical management, almost one-quarter are re-hospitalised for further treatment.

Microbiology of orbital cellulitis with subperiosteal abscess in children: Prevalence and characteristics of Streptococcus anginosus group infection.

PURPOSE: To evaluate the predominant pathogens and clinical course in pediatric patients with orbital cellulitis (OC) complicated by subperiosteal abscess (SPA). METHODS: This is a single-center retrospective chart review evaluating pediatric patients with OC complicated by SPA treated at a tertiary care center in the Pacific Northwest. Data were analyzed for characteristics, rates of infection, and antibiotic resistance of the predominant pathogens in pediatric patients. RESULTS: Twenty-seven children were identified with OC complicated by SPA and bacterial cultures drawn. The average age (SD) of the patients was 9.2 years (4.8), median 9.6; 15 range 5 months to 17.2 years. Seventeen (63.0%) were male. Sinusitis was present in all patients. Streptococcus species were the most common pathogen accounting for 52% (17/33) of isolates. Streptococcus anginosus group (SAG) was the predominant species and were isolated in 10 out of 27 (37%) children in the study. Twenty-one (78%) patients required surgery for the treatment of SPA. Among surgically treated patients, females tended to be younger than males (p = .068). Pediatric patients with SAG infections required more surgery than children without this isolate, 100% and 65%, respectively (p = .030). Female patients tended to have SAG infections more often than males (p = .063). CONCLUSIONS: Orbital infections caused by SAG require surgical management more often than those caused by other pathogens. Our results suggest a difference in pathogenic organisms in male and female patients with SPA. SAG is one of the most common pathogens isolated in orbital cellulitis complicated by SPA in children.

Pangenome analysis and virulence profiling of Streptococcus intermedius.

BACKGROUND: Streptococcus intermedius, a member of the S. anginosus group, is a commensal bacterium present in the normal microbiota of human mucosal surfaces of the oral, gastrointestinal, and urogenital tracts. However, it has been associated with various infections such as liver and brain abscesses, bacteremia, osteo-articular infections, and endocarditis. Since 2005, high throughput genome sequencing methods enabled understanding the genetic landscape and diversity of bacteria as well as their pathogenic role. Here, in order to determine whether specific virulence genes could be related to specific clinical manifestations, we compared the genomes from 27 S. intermedius strains isolated from patients with various types of infections, including 13 that were sequenced in our institute and 14 available in GenBank. RESULTS: We estimated the theoretical pangenome size to be of 4,020 genes, including 1,355 core genes, 1,054 strain-specific genes and 1,611 accessory genes shared by 2 or more strains. The pangenome analysis demonstrated that the genomic diversity of S. intermedius represents an "open" pangenome model. We identified a core virulome of 70 genes and 78 unique virulence markers. The phylogenetic clusters based upon core-genome sequences and SNPs were independent from disease types and sample sources. However, using Principal Component analysis based on presence/ absence of virulence genes, we identified the sda histidine kinase, adhesion protein LAP and capsular polysaccharide biosynthesis protein cps4E as being associated to brain abscess or broncho-pulmonary infection. In contrast, liver and abdominal abscess were associated to presence of the fibronectin binding protein fbp54 and capsular polysaccharide biosynthesis protein cap8D and cpsB. CONCLUSIONS: Based on the virulence gene content of 27 S. intermedius strains causing various diseases, we identified putative disease-specific genetic profiles discriminating those causing brain abscess or broncho-pulmonary infection from those causing liver and abdominal abscess. These results provide an insight into S. intermedius pathogenesis and highlights putative targets in a diagnostic perspective.

Epidemiology and risk factors for pyogenic liver abscess in the Calgary Health Zone revisited: a population-based study.

BACKGROUND: Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone. METHODS: All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999-2003 data, also collected in the CHZ. RESULTS: There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999-2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin. CONCLUSIONS: Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study.