Quercetin protects rats from catheter-related Staphylococcus aureus infections by inhibiting coagulase activity.
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ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC6584481 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Project description:AbstractUncomplicated bacteremia and catheter-related bloodstream infection (CRBSI) are frequently suggested as factors associated with low risk of infective endocarditis in Staphylococcus aureus bacteremia (SAB). Nevertheless, guidelines recommend that echocardiography in all patients with SAB. We evaluated the effects of echocardiography on patient outcomes. Patients with uncomplicated S. aureus CRBSI were retrospectively identified between January 2013 and June 2018 at a 1950-bed, tertiary-care university hospital. Treatment failure was defined as any case of relapse or all-cause death within 90 days. Of 890 SAB patients, 95 with uncomplicated S. aureus CRBSI were included. Thirty-two patients underwent echocardiography within 30 days of their first positive blood culture. Two patients who underwent echocardiography revealed right-sided infective endocarditis. One patient who did not undergo echocardiography experienced recurrent SAB (peripheral CRBSI) 85 days after his first positive blood culture. There were no SAB-related deaths. The Kaplan-Meier curves of treatment failure showed no significant differences between patients who did and did not undergo echocardiography (P = .77). In multivariable analysis, risk factors for treatment failure were liver cirrhosis (hazard ratio: 9.60; 95% confidence interval: 2.13-43.33; P = .003) and other prostheses (hazard ratio: 63.79; 95% confidence interval: 5.05-805.40; P = .001). This study did not verify the putative association between treatment failure and implementation of echocardiography in patients with uncomplicated S. aureus CRBSI. Given the low observed rates of adverse outcomes, routine echocardiography might not be obligatory and could be performed on an individual basis.
| S-EPMC8104220 | biostudies-literature
Project description:Staphylococci are a leading cause of catheter-related infections (CRIs) due to biofilm formation. CRIs are typically managed by either device removal or systemic antibiotics, often in combination with catheter lock solutions (CLSs). CLSs provide high concentrations of the antimicrobial agent at the site of infection. However, the most effective CLSs against staphylococcal biofilm-associated infections have yet to be determined. The purpose of this study was to evaluate the efficacy and suitability of two newly described antimicrobial agents, ML:8 and Citrox, as CLSs against Staphylococcus aureus biofilms. ML:8 (1% [vol/vol]) and Citrox (1% [vol/vol]), containing caprylic acid and flavonoids, respectively, were used to treat S. aureus biofilms grown in vitro using newly described static and flow biofilm assays. Both agents reduced biofilm viability >97% after 24 h of treatment. Using a rat model of CRI, ML:8 was shown to inactivate early-stage S. aureus biofilms in vivo, while Citrox inactivated established, mature in vivo biofilms. Cytotoxicity and hemolytic activity of ML:8 and Citrox were equivalent to those of other commercially available CLSs. Neither ML:8 nor Citrox induced a cytokine response in human whole blood, and exposure of S. aureus to either agent for 90 days was not associated with any increase in resistance. Taken together, these data reveal the therapeutic potential of these agents for the treatment of S. aureus catheter-related biofilm infections.
| S-EPMC5038274 | biostudies-literature
Project description:Staphylococcus aureus (S. aureus) is a frequent cause of catheter-related infections. S. aureus secretes the coagulases staphylocoagulase and von Willebrand factor-binding protein, both of which form a staphylothrombin complex upon binding to prothrombin. Although fibrinogen and fibrin facilitate the adhesion of S. aureus to catheters, the contribution of staphylothrombin-mediated fibrin has not been examined. In this study, we use a S. aureus mutant lacking both coagulases (?coa/vwb) and dabigatran, a pharmacological inhibitor of both staphylothrombin and thrombin, to address this question. Genetic absence or chemical inhibition of pathogen-driven coagulation reduced both fibrin deposition and the retention of S. aureus on catheters in vitro. In a mouse model of jugular vein catheter infection, dabigatran reduced bacterial load on jugular vein catheters, as well as metastatic kidney infection. Importantly, inhibition of staphylothrombin improved the efficacy of vancomycin treatment both in vitro and in the mouse model.
| S-EPMC6281407 | biostudies-literature
Project description:Background:Catheter-related bloodstream infections (CRBSI) with coagulase-negative Staphylococci (CoNS) are a common source of hospital-acquired bloodstream infections. The main objective of this study was to elucidate the role of systemic antibiotic therapy in the setting of catheter removal in adult patients with CoNS-CRBSI. Methods:We conducted a retrospective cohort study on patients with CoNS-CRBSI diagnosed between 2008 and 2016 with follow-up for up to 12 months. The main inclusion criterion was a removed intravascular catheter with quantitative catheter tip culture growing CoNS and the same CoNS identified in the blood culture of a given patient. Outcomes were non-resolved infection (i.e. either presence of prolonged bacteremia or symptoms attributed to CoNS-CRBSI > 2 days after catheter removal), recurrence, mortality and length of hospitalization after catheter removal. We compared outcomes between a group with antibiotic treatment prescribed according to current IDSA guidelines (≥5 days, "treatment" group) and a "no-treatment" group. Results:Our study population comprised 184 CoNS-CRBSI episodes. Seventy-six percent received antibiotic treatment ≥5 days, while 17% did not receive therapy. Non-resolved infections were absent from the patients who did not receive antibiotics. Severe neutropenia, hematologic cancer and immunosuppression were significantly more frequent in the treatment group. The subgroup analysis with 32 matched pairs showed no significant difference in frequency of non-resolved infection (0% in the no-treatment vs 15.6% in the ≥5 days treatment group, p = 0.06). The remaining outcomes were similar in the two groups. Conclusions:Our findings indicate that withholding antimicrobial therapy in CoNS-CRBSI is neither associated with short-term complications nor with long-term recurrences.
| S-EPMC6352346 | biostudies-literature
Project description:The close correlation between the ability of coagulase to clot blood plasma and their capacity to produce disease, and the corresponding absence of this property in nonpathogenic strains, have led to the assumption that the coagulase, plays important role in the pathogenesis of disease. Currently, crystal structure of coagulase in Staphylococcus aureus remains indefinable. Thus, the objectives of this research is to generate the three dimensional model of coagulase in S. aureus by using homology modeling approach. In this study, we used bioinformatics tools and databases such as BLAST (Basic Local Alignment Search Tool), GenBank, PDB (Protein Databank), and Discovery Studio to gain specific functional insights into coagulase. The model was validated using protein structure checking tools such as PROCHECK, Verify 3D and CE (Combinatorial Extension) for reliability. Therefore, structure prediction of coagulase in S. aureus can provide preliminary knowledge for understanding the function of the protein. The information from this finding will provide important information into the action and regulation mechanism of the coagulase protein in S. aureus.
| S-EPMC3374370 | biostudies-literature
Project description:We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications.
| S-EPMC4880091 | biostudies-literature
Project description:Introduction: Current international guidelines strongly recommend catheter removal in case of S. aureus central line-associated bloodstream infection (CLASBI), but a catheter salvage strategy may be considered in children given age-related specificities. No data is available regarding the outcome of this strategy in children. This study aims to evaluate catheter salvage strategy in children with S. aureus CLABSI, and to determine treatment failure rates and associated risk factors. Methods: We retrospectively analyzed data for all children <18 years having S. aureus CLABSI on a long-term central venous catheter in a tertiary hospital from 2010 to 2014. We defined catheter salvage strategy as a central venous catheter left in place ?3 days after initiation of empiric treatment for suspected bacteremia, and catheter salvage strategy failure as the persistence or relapse of bacteremia with a S. aureus strain harboring the same antibiotic susceptibility pattern, or the occurrence or the worsening of local or systemic infectious complication between 72 h and 28 days after the first positive blood culture. Results: During the study period, 49 cases of S. aureus CLABSI on long-term central venous catheters were observed in 41 children (including 59% with long-term parenteral nutrition) and 6 (15%) isolates were resistant to methicillin. A catheter salvage strategy was chosen in 37/49 (76%) cases and failed in 12/37 (32%) cases. Initial presence of bloodstream co-infection, serum concentration of vancomycin under the targeted value and inadequate empiric treatment were significantly associated with catheter salvage therapy failure. Conclusions: The catheter salvage strategy of S. aureus CLABSI on a long-term central venous catheter was frequent in the studied hospital and failed only in one third of cases.
| S-EPMC6355702 | biostudies-literature
Project description:Infections caused by Staphylococcus aureus pose a serious and sometimes fatal health issue. With the aim of exploring a novel therapeutic approach, we chose GraXRS, a Two-Component System (TCS) that determines bacterial resilience against host innate immune barriers, as an alternative target to disarm S. aureus. Following a drug repurposing methodology, and taking advantage of a singular staphylococcal strain that lacks the whole TCS machinery but the target one, we screened 1.280 off-patent FDA-approved drug for GraXRS inhibition. Reinforcing the connection between this signaling pathway and redox sensing, we found that antioxidant and redox-active molecules were capable of reducing the expression of the GraXRS regulon. Among all the compounds, verteporfin (VER) was really efficient in enhancing PMN-mediated bacterial killing, while topical administration of such drug in a murine model of surgical wound infection significantly reduced the bacterial load. Experiments relying on the chemical mimicry existing between VER and heme group suggest that redox active residue C227 of GraS participates in the inhibition exerted by this FDA-approved drug. Based on these results, we propose VER as a promising candidate for sensitizing S. aureus that could be helpful to combat persistent or antibiotic-resistant infections.
| S-EPMC7577973 | biostudies-literature
Project description:AimsTo ascertain the clinical importance of a strain of slide coagulase positive but tube coagulase negative Staphylococcus species isolated from the blood culture of a 43 year old patient with refractory anaemia with excessive blasts in transformation who had neutropenic fever.MethodsThe isolate was investigated phenotypically by standard biochemical methods using conventional biochemical tests and two commercially available systems, the Vitek (GPI) and API (Staph) systems. Genotypically, the 16S ribosomal RNA (rRNA) gene of the bacteria was amplified by the polymerase chain reaction (PCR) and sequenced. The sequence of the PCR product was compared with known 16S rRNA gene sequences in the GenBank by multiple sequence alignment.ResultsConventional biochemical tests did not reveal a pattern resembling a known Staphylococcus species. The Vitek system (GPI) showed that it was 94% S. simulans and 3% S. haemolyticus, whereas the API system (Staph) showed that it was 86.8% S. aureus and 5.1% S. warneri. 16S rRNA gene sequencing showed that there was a 0 base difference between the isolate and S. aureus, 28 base difference between the isolate and S. lugdunensis, 39 base difference between the isolate and S. schleiferi, 21 base difference between the isolate and S. haemolyticus, 41 base difference between the isolate and S. simulans, and 23 base difference between the isolate and S. warneri, indicating that the isolate was a strain of S. aureus. Vancomycin was subsequently prescribed and blood cultures taken four days after the start of treatment were negative.Conclusions16S rRNA gene sequencing was useful in ascertaining the clinical importance of the strain of slide coagulase positive but tube coagulase negative Staphylococcus species isolated from blood culture and allowing appropriate management.
| S-EPMC1187075 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium responsible for serious nosocomial and community-acquired infections worldwide. Since few antibiotics are effective for treating MRSA infections, the development of new therapies is of great importance. Previous studies demonstrated that PBP2a is a target that generates protective antibodies against MRSA. A murine monoclonal antibody (MAb) that recognizes PBP2a from MRSA strains was previously isolated and characterized. In this report, we evaluated the biodistribution of this MAb in blood and tissues, as well as the extent of protection conferred using prophylactic and therapeutic assays compared to vancomycin treatment. Biodistribution was evaluated 12-96 h after MAb administration. It predominantly remained in the serum, but it was also detectable in the kidneys, lungs, and spleen at low concentrations (about 4.5% in the kidneys, 1.9% in the lungs, and 0.7% the spleen) at all observed timepoints. Prophylactic studies in a murine model demonstrated a significant bacterial load reduction in the kidneys of the groups treated with either with IgG (greater than 3 logs) or F(ab')2 (98%) when compared to that of the control groups (untreated). Mice were challenged with a lethal dose, and the survival rate was higher in the treated mice. Treatment with the MAb resulted in a bacterial load reduction in the kidneys similar to that of mice treated with vancomycin, and a MAb/vancomycin combination therapy was also effective. These results demonstrate that an anti-PBP2a MAb may be a promising therapeutic for treating MRSA infections.
| S-EPMC6880988 | biostudies-literature