A Prognostic Model of Persistent Bacteremia and Mortality in Complicated Staphylococcus aureus Bloodstream Infection

Guimaraes, Alessander O.; Cao, Yi; Hong, Kyu; Mayba, Oleg; Peck, Melicent C.; Gutierrez, Johnny; Ruffin, Felicia; Carrasco‐Triguero, Montserrat; Dinoso, Jason B.; Clemenzi-Allen, Angelo; Koss, Catherine A.; Maskarinec, Stacey A.; Chambers, Henry F.; Fowler, Vance G.; Baruch, Amos; Rosenberger, Carrie M.

doi:10.1093/cid/ciy739

Cited by 39 publications

(66 citation statements)

References 38 publications

(50 reference statements)

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“…None of the 8 biomarkers or other clinical metrics evaluated in this study distinguished between IE and non‐IE endovascular infections (Figure c–e, data not shown). We previously reported that median IL‐17A was higher in patients with endovascular foci . Endovascular infections are associated with persistent bacteraemia, and these three biomarkers were also associated with persistent bacteraemia (Figure c–e).…”

Section: Resultsmentioning

confidence: 61%

“…The ability to identify patients with IE at admission could direct their clinical work‐up, including diagnostic imaging. Higher levels of IL‐17A and IL‐10 preceded the diagnosis of IE [first positive transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE)] by several days to weeks in some patients (Figure ), previously observed for IL‐17A . Thresholds for IL‐17A and IL‐10 identified 71% and 65%, respectively, of IE patients diagnosed after day 3, the time by when samples were available for biomarker measurements (Figure ).…”

Section: Resultsmentioning

confidence: 79%

“…However, critical determinants of immune evasion in patients with SAB remain poorly understood and connections between the immune response and microbiological failure are lacking. Previous studies identified several candidate innate immunity biomarkers that were independently associated with mortality and prolonged SAB, supporting the utility of biomarkers to distinguish patients prone to developing severe disease . Such information would be particularly beneficial in guiding diagnostic work‐up of patients at increased risk of S. aureus infective endocarditis (IE), a disease that even with the best available treatments has contemporary in‐hospital mortality rates ranging from 25 to 46% …”

Section: Introductionmentioning

confidence: 93%

“…Mortality rates for patients with Staphylococcus aureus bacteraemia (SAB) largely remain unchanged despite significant advances in clinical management, with new antibiotic therapies and rapid diagnostics available in recent decades. Significant heterogeneity in the clinical course of patients with SAB despite appropriate antibiotic therapy suggests that differential host immune response may contribute to adverse patient outcomes . However, critical determinants of immune evasion in patients with SAB remain poorly understood and connections between the immune response and microbiological failure are lacking.…”

Section: Introductionmentioning

confidence: 99%

“…To investigate the contribution of the differential immune response to SAB disease severity, we previously identified biomarker profiles associated with mortality and persistent bacteraemia in a two‐phase case–control study of patients with complicated SAB. There, we evaluated a panel of 13 candidate biomarkers in patients with complicated SAB enriched for persistent bacteraemia and mortality and observed that high IL‐17A, IL‐10 and soluble E‐selectin (sE‐selectin) levels at presentation were prognostic for persistent bacteraemia, while high levels of IL‐8 and CCL2 were prognostic for mortality . In the validation cohort presented herein, we evaluated the top 8 biomarkers with the strongest prognostic value in an unselected population of 160 patients with SAB consecutively enrolled at a single centre over a three‐year period.…”

Section: Introductionmentioning

confidence: 99%

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Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Cao¹,

Guimaraes²,

Peck³

et al. 2020

Clin & Trans Imm

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Objectives To identify risk stratification biomarkers to enrich for the subset of Staphylococcus aureus bacteraemia patients who develop deep‐seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management. Methods We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with S. aureus bacteraemia enrolled consecutively over 3 years. Results High levels of IL‐17A, IL‐10 or soluble E‐selectin at bacteraemia diagnosis correlated with the duration of positive blood cultures. When thresholds defined in an independent cohort were applied, these biomarkers were robust predictors of persistent bacteraemia or endovascular infection. High serum levels of IL‐17A and IL‐10 often preceded the radiographic diagnosis of infective endocarditis, suggesting potential utility for prioritising diagnostic radiographic imaging. High IL‐8 was prognostic for all‐cause mortality, while IL‐17A and IL‐10 were superior to clinical metrics in discriminating between attributable mortality and non‐attributable mortality. High IL‐17A and IL‐10 identified more patients who developed microbiological failure or mortality than were identified by infective endocarditis diagnosis. Conclusion These biomarkers offer potential utility to identify patients at risk of persistent bacteraemia to guide diagnostic imaging and clinical management. Low biomarker levels could be used to rule out the need for more invasive TEE imaging in patients at lower risk of infective endocarditis. These biomarkers could enable clinical trials by enriching for patients with the greatest need for novel therapies.

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Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Cao¹,

Guimaraes²,

Peck³

et al. 2020

Clin & Trans Imm

Self Cite

View full text Add to dashboard Cite

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Antimicrobial effect of pimozide by targeting ROS‐mediated killing in Staphylococcus aureus

Kumar

Kharb

Kumar

et al. 2023

Biotech and App Biochem

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In spite of the higher nosocomial and community‐acquired infections caused by Staphylococcus aureus, emerging drug resistance is a leading cause of increased mortality and morbidity associated with the overuse of antimicrobials. It is an emergent need to find out new molecules to combat such infections. In the present study, we analyzed the antibacterial effect of pimozide (PMZ) against gram‐positive and gram‐negative bacterial strains, including methicillin‐sensitive (MSSA) and methicillin‐resistant (MRSA) S. aureus. The growth of MSSA and MRSA was completely inhibited at concentrations of 12.5 and 100 μg/mL, respectively, which is referred to as 1× minimum inhibitory concentration (MIC). The cell viability was completely eliminated within 90 min of PMZ treatment (2× MIC) through reactive oxygen species (ROS)‐mediated killing without affecting cell membrane permeability. It suppressed α‐hemolysin production and biofilm formation of different S. aureus strains by almost 50% at 1× MIC concentration, and was found to detach matured biofilm. PMZ treatment effectively eliminates S. aureus infection in Caenorhabditis elegans and improves its survival by 90% and is found safe to use with no hemolytic effect on human and chicken blood tissues. Taken together, it is concluded that PMZ may turn out to be an effective antibacterial for treating bacterial infections including MSSA and MRSA.

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