Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures.
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ABSTRACT:
SUBMITTER: Wozniak JM
PROVIDER: S-EPMC7494005 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPersistent Staphylococcus aureus bacteremia (SAB) is defined based on varying duration in literature. The primary objective was to determine the risk of poor outcomes in relation to bacteremia duration.MethodsMulticenter, prospective, observational study of adult hospitalized patients with SAB. Medical records were reviewed for pertinent data. Patients were grouped by bacteremia duration: short (1-2 days), intermediate (3-6 days), and prolonged (≥7 days) and compared for risk factors and outcomes.ResultsOf 884 patients, 63% had short, 28% intermediate, and 9% prolonged bacteremia. Overall mean age was 57 years, and 70% were male. The prolonged group had the highest proportion of methicillin-resistant SAB (P < .0001). Choice of antibiotic therapy did not significantly affect bacteremia duration; however, time to source-control procedure was delayed in the prolonged and intermediate groups compared with the short group (3.5 vs 3 vs 1 day, P < .0001). Metastatic complications, length of stay, and 30-day mortality were progressively worse as bacteremia duration increased (P < .0001). Every continued day of bacteremia was associated with a relative risk of death of 1.16 (95% confidence interval, 1.10-1.22; P < .0001), with a significant increase in risk starting at 3 days as determined by receiver operating characteristic analysis.ConclusionsOptimal management of SAB should target bacterial clearance as soon as possible to minimize incremental risk of mortality with each day of positive blood culture. Delay in source control but not type of antistaphylococcal therapy was significantly associated with prolonged bacteremia and worse outcomes.
| S-EPMC7768749 | biostudies-literature
Project description:BackgroundStaphylococcus aureus bacteremia (SaB) carries considerable morbidity and mortality. We examined the predictive value of serum concentrations of interleukin (IL)-10, proinflammatory cytokines, and terminal complement on patient survival and SaB duration.MethodsClinical information on consecutive patients with SaB at a tertiary medical center were collected prospectively. Patient serum samples obtained at the day of clinical presentation were assayed for tumor necrosis factor-?, IL-1?, IL-10, and complement membrane attack complex C5b-9 concentrations using enzyme-linked immunoassay. Logistic regression identified predictors of mortality and duration of bacteremia.ResultsIn 59 patients with SaB, 14% died and 17% had prolonged bacteremia (>4 days). Elevated IL-10 serum concentrations (>7.8 pg/mL) identified all 8 patients who died, whereas there were no deaths in patients with normal IL-10 (P = .016). The lack of an IL-1? response (?0.45 pg/mL) defined all patients with SaB >4 days. In multivariate analysis, patient age (odds ratio [OR], 1.16; P = .022), duration of bacteremia (OR, 1.16; P = .031), and serum IL-10 (OR, 1.05; P = .014) were identified as independent predictors of patient mortality.ConclusionsSaB mortality was confined strictly to patients with elevated IL-10 concentrations. We recommend that future clinical trials of SaB stratify patients according to IL-10 and IL-1? serum concentrations in order to better evaluate the impact of therapeutic interventions on patient outcome.
| S-EPMC6281403 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.
| S-EPMC5204005 | biostudies-other
Project description:To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.
| S-EPMC3882664 | biostudies-literature
Project description:The Infectious Diseases Society of America infection-specific guidelines provide limited guidance on the management of focal infections complicated by secondary bacteremias. We address the following 3 commonly encountered questions and management considerations regarding uncomplicated bacteremia not due to Staphylococcus aureus: the role and choice of oral antibiotics focusing on oral beta-lactams, the shortest effective duration of therapy, and the role of repeat blood cultures.
| S-EPMC5952922 | biostudies-other
Project description:Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia.To review evidence of management strategies for S. aureus bacteremia to determine whether transesophageal echocardiography is necessary in all adult cases and what is the optimal antibiotic therapy for methicillin-resistant S. aureus (MRSA) bacteremia.A PubMed search from inception through May 2014 was performed to identify studies addressing the role of transesophageal echocardiography in S. aureus bacteremia. A second search of PubMed, EMBASE, and the Cochrane Library from January 1990 through May 2014 was performed to find studies addressing antibiotic treatment for MRSA bacteremia. Studies reporting outcomes from antibiotic therapy for MRSA bacteremia were included. All searches, which were limited to English and focused on adults, were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation system with consensus of independent evaluations by at least 2 of the authors.In 9 studies with a total of 4050 patients, use of transesophageal echocardiography was associated with higher rates of a diagnosis of endocarditis (14%-28%) compared with transthoracic echocardiography (2%-15%). In 4 studies, clinical or transthoracic echocardiography findings did not predict subsequent transesophageal echocardiography findings of endocarditis. Five studies identified clinical or transthoracic echocardiography characteristics associated with low risk of endocarditis (negative predictive values from 93% to 100%). Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S. aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis. Of 81 studies of antibiotic therapy for MRSA bacteremia, only 1 high-quality trial was identified. In that study of 246 patients with S. aureus bacteremia, daptomycin was not inferior to vancomycin or an antistaphylococcal penicillin, each in combination with low-dose, short-course gentamicin (clinical success rate, 44.2% [53/120] vs 41.7% [48/115]; absolute difference, 2.4% [95% CI, -10.2% to 15.1%]).All adult patients with S. aureus bacteremia should undergo echocardiography. Characteristics of low-risk patients with S. aureus bacteremia for whom transesophageal echocardiography can be safely avoided have been identified. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of S. aureus bacteremia are needed.
| S-EPMC4263314 | biostudies-other
Project description:BackgroundTo understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB).MethodsAll SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array.ResultsR-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402-17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696-10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10).ConclusionThis study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study.
| S-EPMC8315037 | biostudies-literature
Project description:S. aureus bacteremia (SAB) is a common condition with high rates of morbidity and mortality. Current methods used to diagnose SAB take at least a day, and often longer. Patients with suspected bacteremia must therefore be empirically treated, often unnecessarily, while assay results are pending. In this proof-of-concept study, we describe an inexpensive assay that detects SAB via the detection of micrococcal nuclease (an enzyme secreted by S. aureus) in patient plasma samples in less than three hours. In total, 17 patient plasma samples from culture-confirmed S. aureus bacteremic individuals were tested. 16 of these yielded greater nuclease assay signals than samples from uninfected controls or individuals with non-S. aureus bacteremia. These results suggest that a nuclease-detecting assay may enable the rapid and inexpensive diagnosis of SAB, which is expected to substantially reduce the mortality and morbidity that result from this condition.
| S-EPMC4909304 | biostudies-literature
Project description:IntroductionClear cut-off levels could aid clinicians in identifying patients with a risk of fatal outcomes or complications such as deep infection foci in Staphylococcus aureus bacteremia (SAB). Cut-off levels for widely used clinical follow-up parameters including serum C-reactive protein (CRP) levels and white blood cell counts (WBC) have not been previously studied.Methods430 adult SAB patients in Finland took part in prospective multicentre study in which their CRP levels and WBC counts were measured on the day of the positive blood culture, every other day during the first week, twice a week during hospitalization and at 30 days. Receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CRP and WBC on the day of the positive blood culture and at days 4, 7, and 14 in predicting mortality and the presence of deep infections at 30 days. Adjusted hazard ratios (HR) for CRP level and WBC count cut-off values for mortality were calculated by the Cox regression analysis and adjusted odds ratios (OR) for cut-off values to predict the presence of deep infection by the binary logistic regression analysis.ResultsThe succumbing patients could be distinguished from the survivors, starting on day 4 after the positive blood culture, by higher CRP levels. Cut-off values of CRP for day 30 mortality in adjusted analysis, that significantly predicted fatal outcome were at day 4 CRP >103 mg/L with sensitivity of 77%, specificity of 55%, and HR of 3.5 (95% CI, 1.2-10.3; p = 0.024), at day 14 CRP >61 mg/L with a sensitivity of 82%, specificity of 80% and HR of 3.6 (95% CI, 1.1-10.3; p<0.039) and cut-off value of WBC at day 14 >8.6 x109/L was prognostic with sensitivity of 77%, specificity of 78% and HR of 8.2 (95% CI, 2.9-23.1; p<0.0001). Cut-off values for deep infection in adjusted analysis were on the day of the positive blood culture CRP >108 mg/L with sensitivity of 77%, specificity of 60%, and HR of 2.6 (95% CI, 1.3-4.9; p = 0.005) and at day 14 CRP >22 mg/L with sensitivity of 59%, specificity of 68%, and HR of 3.9 (95% CI, 1.6-9.5; p = 0.003). The lack of decline of CRP in 14 days or during the second week were neither prognostic nor markers of deep infection focus.ConclusionsCRP levels have potential for the early identification of SAB patients with a greater risk for death and deep infections.
| S-EPMC4868312 | biostudies-literature
Project description:BackgroundMany studies have shown that vancomycin is inferior to β-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving β-lactam antibiotics for MSSA bacteremia.MethodsEighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and β-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion.ResultsPittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the β-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or β-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving β-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively).ConclusionsThere were no significant difference in clinical outcomes between initial teicoplanin treatment and β-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality.
| S-EPMC8117599 | biostudies-literature