Staphylococcus Aureus Infective Endocarditis: JACC Patient Pathways.
Ontology highlight
ABSTRACT:
SUBMITTER: Grapsa J
PROVIDER: S-EPMC8743816 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:S. aureus has a propensity to cause endocarditis; diabetes mellitus is a frequent underlying comorbitity in patents with S. aureus endocarditis. S. aureus Affymetrix GeneChips were used to compare S. aureus expression properties in cardiac vegatations isolated from diabetic and nondiabetic rats. S. aureus Affymetrix GeneChips were also used to compare the S. aureus expression properties of cardiac vegatations (both diabetic and nondiabetic) in comparsions to planktonic cells. Few differences were observed between the expression properties of S. aureus harvested from diabetic vs. nondiabetic cardiac vegatations. Significant differences were observed between the expression properties of S. aureus harvested from cardiac vegetations in comparison to exponential and/or stationary phase planktonically grown cells.
2014-11-01 | GSE62390 | GEO
Project description:S. aureus has a propensity to cause endocarditis; diabetes mellitus is a frequent underlying comorbitity in patents with S. aureus endocarditis. S. aureus Affymetrix GeneChips were used to compare S. aureus expression properties in cardiac vegatations isolated from diabetic and nondiabetic rats. S. aureus Affymetrix GeneChips were also used to compare the S. aureus expression properties of cardiac vegatations (both diabetic and nondiabetic) in comparsions to planktonic cells. Few differences were observed between the expression properties of S. aureus harvested from diabetic vs. nondiabetic cardiac vegatations. Significant differences were observed between the expression properties of S. aureus harvested from cardiac vegetations in comparison to exponential and/or stationary phase planktonically grown cells. S. aureus strain COL was used to establish cardiac vegetations in diabetic and nondiabetic rats or grown in laboratory medium to exponential or stationary phase, total bacterial RNA was isolated, labeled and applied to Affymetrix GeneChips. We sought to determine whether the transcriptional profiles of S. aureus differed in diabetic vs. nondiabetic rats and whether vegetations differed from that of planktonic S. aureus.
2014-11-01 | E-GEOD-62390 | biostudies-arrayexpress
Project description:BackgroundDiabetes mellitus is a frequent underlying comorbidity in patients with Staphylococcus aureus endocarditis, and it represents a risk factor for complications and a negative outcome. The pathogenesis of staphylococcal endocardial infections in diabetic hosts has been poorly characterized, and little is known about S. aureus gene expression in endocardial vegetations.MethodsWe utilized a rat model of experimental S. aureus endocarditis to compare the pathogenesis of staphylococcal infection in diabetic and nondiabetic hosts and to study the global S. aureus transcriptome in endocardial vegetations in vivo.ResultsDiabetic rats had higher levels of bacteremia and larger endocardial vegetations than nondiabetic control animals. Microarray analyses revealed that 61 S. aureus genes were upregulated in diabetic rats, and the majority of these bacterial genes were involved in amino acid and carbohydrate metabolism. When bacterial gene expression in vivo (diabetic or nondiabetic endocardial vegetations) was compared to in vitro growth conditions, higher in vivo expression of genes encoding toxins and proteases was observed. Additionally, genes involved in the production of adhesins, capsular polysaccharide, and siderophores, as well as in amino acid and carbohydrate transport and metabolism, were upregulated in endocardial vegetations. To test the contribution of selected upregulated genes to the pathogenesis of staphylococcal endocarditis, isogenic deletion mutants were utilized. A mutant defective in production of the siderophore staphyloferrin B was attenuated in the endocarditis model, whereas the virulence of a surface adhesin (ΔsdrCDE) mutant was similar to that of the parental S. aureus strain.ConclusionsOur results emphasize the relevance of diabetes mellitus as a risk factor for infectious endocarditis and provide a basis for understanding gene expression during staphylococcal infections in vivo.
| S-EPMC4228149 | biostudies-literature
Project description:Staphylococcus aureus is an important cause of community-associated bacteremia (SAB) and infective endocarditis (IE). No significant differences in distribution or frequency of genes encoding virulence factors, including genes encoding adhesins, were found between isolates from the IE and SAB groups (12 IE and 10 SAB patients).
| S-EPMC2812277 | biostudies-literature
Project description:Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that superantigens are critical in the causation of all three infections. We show that their association results from both superantigenicity and direct toxic effects on endothelial cells, the latter likely contributing to delayed endothelium healing. Our studies contribute significantly to understanding the development of these illnesses and are expected to lead to development of important therapies to treat such illnesses.
| S-EPMC3747586 | biostudies-literature
Project description:We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.
| S-EPMC5328541 | biostudies-literature
Project description:The microbiological characteristics of Staphylococcus aureus causing infective endocarditis (IE) have not been investigated thoroughly. We compared the characteristics of S. aureus isolates from patients with and without IE. Cases of S. aureus bacteremia (SAB) were collected from 10 hospitals over 7 years. Cases of native valve IE were matched with non-IE controls according to the following criteria: central-line-associated infection, community-acquired infection, methicillin susceptibility, and if possible, the primary site of infection. Genes coding virulence factors were analyzed using multiplex polymerase chain reactions. Fibrinogen and fibronectin-binding properties were assessed using in vitro binding assays. The fibronectin-binding protein A gene (fnbpA) was sequenced. Of 2,365 cases of SAB, 92 had IE. After matching, 37 pairs of S. aureus isolates from the IE cases and non-IE controls were compared; fnbpA was detected in 91.9% of the IE isolates and 100% of the non-IE isolates (p = 0.24). While the fibrinogen binding ratio was similar (1.07 ± 0.33 vs. 1.08 ± 0.26, p = 0.89), the fibronectin-binding ratio was significantly higher in the IE-group (1.31 ± 0.42 vs. 1.06 ± 0.31, p = 0.01). The proportions of major single-nucleotide polymorphisms in fnbpA were as follows: E652D (2.9% vs. 2.7%), H782Q (65.6% vs. 60.6%), and K786N (65.6% vs. 72.7%). The fibronectin-binding ratio was positively correlated with the number of SNPs present in IE cases (p < 0.001) but not in the non-IE controls (p = 0.124). Fibronectin-binding might play a key role in SAB IE. However, the degree of binding may be mediated by genetic variability between isolates.
| S-EPMC8647854 | biostudies-literature
Project description:Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05-0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53-192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej, and ser (sedjr; adjusted OR 0.07; 95% CI 0.004-0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.
| S-EPMC6003251 | biostudies-literature
Project description:Background The potential of phage therapy for the treatment of endovascular Staphylococcus aureus infections remains to be evaluated. Methods and Results The efficacy of a phage cocktail combining Herelleviridae phage vB_SauH_2002 and Podoviriae phage 66 was evaluated against a methicillin-sensitive S. aureus strain in vitro and in vivo in a rodent model of experimental endocarditis. Six hours after bacterial challenge, animals were treated with (1) the phage cocktail. (2) subtherapeutic flucloxacillin dosage, (3) combination of the phage cocktail and flucloxacillin, or (4) saline. Bacterial loads in cardiac vegetations at 30 hours were the primary outcome. Secondary outcomes were phage loads at 30 hours in cardiac vegetations, blood, spleen, liver, and kidneys. We evaluated phage resistance 30 hours post infection in vegetations of rats under combination treatment. In vitro, phages synergized against S. aureus planktonic cells and the cocktail synergized with flucloxacillin to eradicated biofilms. In infected animals, the phage cocktail achieved bacteriostatic effect. The addition of low-dose flucloxacillin elevated bacterial suppression (∆ of -5.25 log10 colony forming unit/g [CFU/g] versus treatment onset, P<0.0001) and synergism was confirmed (∆ of -2.15 log10 CFU/g versus low-dose flucloxacillin alone, P<0.01). Importantly, 9/12 rats given the combination treatment had sterile vegetations at 30 hours. In vivo phage replication was partially suppressed by the antibiotic and selection of resistance to the Podoviridae component of the phage cocktail occurred. Plasma-mediated inhibition of phage killing activity was observed in vitro. Conclusions Combining phages with a low-dose standard of care antibiotic represents a promising strategy for the treatment of S. aureus infective endocarditis.
| S-EPMC9238497 | biostudies-literature
Project description:Echocardiography is fundamental for diagnosing infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB), but whether all such patients require transesophageal echocardiography (TEE) is controversial.We identified SAB cases between February 2008 and April 2012. We compared sensitivity and specificity of transthoracic echocardiography (TTE) and TEE for evidence of IE, and we determined impacts of IE risk factors and TTE image quality on comparative sensitivities of TTE and TEE and their impact on clinical decision making.Of 215 evaluable SAB cases, 193 (90%) had TTE and 130 (60%) had TEE. In 119 cases with both tests, IE was diagnosed in 29 (24%), for whom endocardial involvement was evident in 25 (86%) by TEE, vs only 6 (21%) by TTE (P < .001). Transesophageal echocardiography was more sensitive than TTE regardless of risk factors. Even among the 66 cases with adequate or better quality TTE images, sensitivity was only 4 of 17 (24%) for TTE, vs 16 of 17 (94%) for TEE (P < .001). Among 130 patients with TEE, the TEE results, alone or with TTE results, influenced treatment duration in 56 (43%) cases and led to valve surgery in at least 4 (6%). It is notable that, despite vigorous efforts to obtain both tests routinely, TEE was not done in 86 cases (40%) for various reasons, including pathophysiological contraindications (14%), patient refusal or other patient-related factors (16%), and provider declination or system issues (10%).Patients with SAB should undergo TEE when possible to detect evidence for IE, especially if the results might affect management.
| S-EPMC5407216 | biostudies-literature