Moxifloxacin Monotherapy in Left-Sided Staphylococcus aureus Endocarditis.
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ABSTRACT:
SUBMITTER: Colkesen Y
PROVIDER: S-EPMC8060113 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundStaphylococcus aureus is the most frequent and fatal cause of left-sided infective endocarditis (IE). New treatment strategies are needed to improve the outcome. S. aureus coagulase promotes clot and fibrin formation. We hypothesized that dabigatran, could reduce valve vegetations and inflammation in S. aureus IE.MethodsWe used a rat model of severe aortic valve S. aureus IE. All infected animals were randomized to receive adjunctive dabigatran (10 mg/kg b.i.d., n = 12) or saline (controls, n = 11) in combination with gentamicin. Valve vegetation size, bacterial load, cytokine, cell integrins expression and peripheral platelets and neutrophils were assessed 3 days post-infection.ResultsAdjunctive dabigatran treatment significantly reduced valve vegetation size compared to controls (p< 0.0001). A significant reduction of the bacterial load in aortic valves was seen in dabigatran group compared to controls (p = 0.02), as well as expression of key pro-inflammatory markers keratinocyte-derived chemokine, IL-6, ICAM-1, TIMP-1, L-selectin (p< 0.04). Moreover, the dabigatran group had a 2.5-fold increase of circulating platelets compared to controls and a higher expression of functional and activated platelets (CD62p+) unbound to neutrophils.ConclusionAdjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE.
| S-EPMC6474597 | biostudies-literature
Project description:Higher vancomycin MICs have been associated with more complicated courses and higher mortality rates in patients with Staphylococcus aureus bacteremia and infective endocarditis (IE). The aim of this study was to investigate whether the strains belonging to the cohort of 93 patients from a previously published study in which patients with strains with vancomycin MICs of ?1.5??g/ml presented higher mortality rates and systemic emboli than patients with strains with vancomycin MICs of <1.5??g/ml had specific patterns of virulence factors, clonal complex (CC) types, or the ability to form biofilms. Vancomycin MICs were determined by Etest, and the isolates underwent spa typing to infer the CC, biofilm studies, a thrombin-induced platelet microbicidal assay, and multiplex PCR for the presence of virulence genes. We found no differences in genes encoding adhesins, toxins, or other putative virulence genes according to the vancomycin MIC group. CC30, CC34, and CC45 represented nearly half of the isolates, and there was no association with the vancomycin MIC. agr subgroups I and III predominated, with no association with the vancomycin MIC. Isolates with higher vancomycin MICs exhibited a poorer ability to form biofilms with and without the presence of vancomycin (2.03 versus 2.48 [P?<?0.001], respectively, for isolates with higher vancomycin MICs and 2.60 versus 2.87 [P?=?0.022], respectively, for isolates with lower vancomycin MICs). In the multivariable analysis, efb and V8 were risk factors for major emboli (adjusted odds ratio [aOR] = 7.5 and 95% confidence interval [CI] = 1.2 to 46.6 for efb, and aOR = 3.9 and 95% CI = 1.1 to 14.1 for V8), whereas no genotypic predictors of in-hospital mortality were found. No clear associations between genes encoding virulence factors, agr type, clonal complexes, mortality, and major embolic events according to vancomycin MIC group were found.
| S-EPMC7038266 | biostudies-literature
Project description:We utilized the rabbit model of aortic valve infective endocarditis to examine the combined efficacy of the lysin LSVT-1701 plus daptomycin. The combination of LSVT-1701 plus daptomycin was highly effective at reducing methicillin-resistant Staphylococcus aureus (MRSA) counts in target tissue. When given for four daily doses, both lysin dose regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as an adjunctive therapy for the treatment of invasive MRSA infections.
| S-EPMC8284455 | biostudies-literature
Project description:Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown.Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52-5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35-6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21-3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26-3.78; P=0.004) were the only independent predictors of 1-year mortality.S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.
| S-EPMC4503384 | biostudies-literature
Project description:OBJECTIVES:Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ?1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (?1.5 mg/L) phenotype. METHODS:All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal ?-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (?1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. RESULTS:Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). CONCLUSIONS:In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal ?-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.
| S-EPMC5816984 | biostudies-literature
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:IntroductionAccurate prediction of embolic events in infective endocarditis could inform critical clinical decisions, such as the timing of cardiac surgical intervention. However, many embolic events occur before hospital admission and echocardiography and are thus non-modifiable. We aimed to identify time-sensitive variables that predict embolic events in infective endocarditis, focusing on those that occur after diagnosis.MethodsClinical, microbiological, and echocardiographic characteristics were collected from 116 patients with definite or probable left-sided infective endocarditis admitted to Sunnybrook Health Sciences Centre (Toronto, Canada) between October 2013 and July 2016; associations between these characteristics and embolic events were identified using simple logistic regression.ResultsThe mean (SD) age was 66 (17) years; 82 patients (71%) were men. The most frequent microorganisms were Staphylococcus aureus (23%) and viridans group streptococci (21%). Seventy-nine (68%) patients had left-sided vegetations, with involvement of the aortic valve in 34 (43%) patients, mitral valve in 37 (47%) patients, and both in 8 (10%) patients. The mean (SD) vegetation size was 10 (7) mm. Forty-three unique patients (37%) had 50 embolic events, with most (34/43; 79%) having a first embolic event (38/50; 76%) before or on the day of echocardiography. There were no significant predictors of the 11 patients with an embolic event after echocardiography; significant predictors of an embolic event at any time were single valve vegetation vs. no vegetation (OR, 4.75; 95% confidence interval [CI], 1.76-12.78) and, among patients with a vegetation, mitral vs. aortic valve location (OR, 4.43; 95%CI, 1.63-12.04).ConclusionsAssociations between patient and echocardiographic characteristics and embolism in patients with infective endocarditis may be time-sensitive, as few embolic events occurred after clinical and echocardiographic assessment.
| S-EPMC6483226 | biostudies-literature
Project description:To update the epidemiology of S. aureus bloodstream infection (SAB) in a high-income country and its link with infective endocarditis (IE).All consecutive adult patients with incident SAB (n = 2008) were prospectively enrolled between 2009 and 2011 in 8 university hospitals in France.SAB was nosocomial in 54%, non-nosocomial healthcare related in 18% and community-acquired in 26%. Methicillin resistance was present in 19% of isolates. SAB Incidence of nosocomial SAB was 0.159/1000 patients-days of hospitalization (95% confidence interval [CI] 0.111-0.219). A deep focus of infection was detected in 37%, the two most frequent were IE (11%) and pneumonia (8%). The higher rates of IE were observed in injecting drug users (IE: 38%) and patients with prosthetic (IE: 33%) or native valve disease (IE: 20%) but 40% of IE occurred in patients without heart disease nor injecting drug use. IE was more frequent in case of community-acquired (IE: 21%, adjusted odds-ratio (aOR) = 2.9, CI = 2.0-4.3) or non-nosocomial healthcare-related SAB (IE: 12%, aOR = 2.3, CI = 1.4-3.5). S. aureus meningitis (IE: 59%), persistent bacteremia at 48 hours (IE: 25%) and C-reactive protein > 190 mg/L (IE: 15%) were also independently associated with IE. Criteria for severe sepsis or septic shock were met in 30% of SAB without IE (overall in hospital mortality rate 24%) and in 51% of IE (overall in hospital mortality rate 35%).SAB is still a severe disease, mostly related to healthcare in a high-income country. IE is the most frequent complication and occurs frequently in patients without known predisposing conditions.
| S-EPMC4447452 | biostudies-other
Project description:PurposeTo prospectively evaluate the prevalence of the embolization of the spleen in patients with definite left-sided infective endocarditis (IE) using a contrast-enhanced ultrasound (CEUS).MethodsFrom March 2012 through September 2013, 18 consecutive patients (9 females and 9 males, aged 21-83 years) evaluated at our hospital and with definite left-sided IE according to the revised Duke criteria were enrolled. All of the patients gave informed written consent and the study was performed in conformity with the ethical guidelines of the Declaration of Helsinki. All of the patients were submitted to a CEUS of the spleen within 10 days after the definite diagnosis of IE. For the CEUS, a blood pool second-generation contrast agent and an ultrasound machine with a contrast harmonic imaging technology were used.ResultsThe splenic CEUS showed infarctions in 11 patients (61 %) and resulted positive in the 2 patients with negative echocardiography.ConclusionsIn this study, CEUS of the spleen, a repeatable and low-cost imaging technique, easily allowed the bedside detection of asymptomatic and even tiny infarctions and showed a high rate of embolization in patients with definite left-sided IE. Therefore, in the setting of IE (possible or definite), CEUS of the spleen has the potential to better define or accelerate the diagnosis itself.
| S-EPMC4529419 | biostudies-literature
Project description:Purpura fulminans (PF) is a haematologic emergency that can occur in the setting of severe septic shock. Its pathophysiology is not well-understood; however, some evidence suggests it may be mediated by excessive protein C consumption. In this case report, we describe a patient with PF secondary to methicillin-resistant Staphylococcus aureus endocarditis. She presented with severe septic shock and, despite haemodynamic improvement, developed a significant purpuric rash. Diagnostic work-up was notable for severely decreased serum levels of protein C. This patient was successfully treated with protein C concentrate and surgical valve replacement. While PF is rarely associated with S. aureus infection, this presentation may be more frequently encountered among clinicians in the current opioid epidemic. Quick recognition is crucial and a multidisciplinary approach, including intravenous infusion of protein C, may be considered.
| S-EPMC6601163 | biostudies-literature