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Prognostic Power of Pathogen Cell-Free DNA in Staphylococcus aureus Bacteremia.

ABSTRACT: Background:Staphylococcus aureus is a leading global cause of bacteremia that can cause invasive tissue infections with high morbidity and mortality despite appropriate antibiotic therapy. Clinicians lack sufficient tools to rapidly identify patients with a poor prognosis to guide diagnostic workup and treatment decisions. Host cell-free DNA provides prognostic value across a spectrum of critical illnesses, including S. aureus bacteremia and sepsis. Metrics of high bacterial load are associated with disease severity in S. aureus bacteremia, and the objective of this study was to evaluate whether incorporating quantitation of cell-free bacterial DNA would provide additive prognostic value when combined with biomarkers of the inflammatory response. Methods:S. aureus cell-free DNA was measured by quantitative polymerase chain reaction (PCR) in baseline serum samples from an observational cohort of 111 patients with complicated S. aureus bacteremia and correlated with host inflammatory markers and clinical outcomes. Results:High levels of S. aureus cell-free DNA at the time of positive index blood culture were prognostic for all-cause and attributable mortality and persistent bacteremia and were associated with infective endocarditis. However, they did not provide additive value to biomarkers of the host response to infection in multivariate analysis. Conclusions:Measurements of bacterial load by PCR are a clinically feasible candidate biomarker for stratifying patients at higher risk for complications and poor outcomes. Their diagnostic and prognostic value for identifying foci of infection and influencing treatment remain to be evaluated in additional cohorts.

SUBMITTER: Guimaraes AO

PROVIDER: S-EPMC6483138 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Prognostic Power of Pathogen Cell-Free DNA in <i>Staphylococcus aureus</i> Bacteremia.

Guimaraes Alessander O AO Gutierrez Johnny J Maskarinec Stacey A SA Cao Yi Y Hong Kyu K Ruffin Felicia F Carrasco-Triguero Montserrat M Peck Melicent C MC Fowler Vance G VG Baruch Amos A Rosenberger Carrie M CM

Open forum infectious diseases 20190315 4

<h4>Background</h4><i>Staphylococcus aureus</i> is a leading global cause of bacteremia that can cause invasive tissue infections with high morbidity and mortality despite appropriate antibiotic therapy. Clinicians lack sufficient tools to rapidly identify patients with a poor prognosis to guide diagnostic workup and treatment decisions. Host cell-free DNA provides prognostic value across a spectrum of critical illnesses, including <i>S. aureus</i> bacteremia and sepsis. Metrics of high bacteria ...[more]

PMID: 31041341

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Project description:ObjectiveTo identify risk factors and outcomes associated with thrombocytopenia at sepsis onset in Staphylococcus aureus bacteremia.Patients and methodsThis single-center, retrospective, cohort study consists of all adult patients with a first episode of clinical S aureus bacteremia between April 1, 1988, and September 30, 1994, and between January 1, 1999, and December 31, 2007. Thrombocytopenia was defined as a platelet count less than 150 × 10(9)/L. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified using univariate and multivariable analyses. Multivariable analysis was conducted using forward step logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for risk of death.ResultsA total of 1052 patients had clinical S aureus bacteremia. Thrombocytopenia at sepsis onset was present in 235 patients (22.3%). Thrombocytopenia was associated with community-acquired bacteremia, infections caused by methicillin-sensitive S aureus, high-magnitude bacteremia (defined as >4 positive blood cultures [? 3 separate positive blood culture sets]), and endocarditis. Patients with thrombocytopenia presented more commonly with severe sepsis reflected by septic shock and acute renal failure. Thirty-day mortality was significantly higher among patients with thrombocytopenia (132/235 [56.2%]) vs those without thrombocytopenia (281/817 [34.4%]; P<.001). Higher mortality was associated with the degree of thrombocytopenia. In multivariable analysis, thrombocytopenia at baseline remained an independent risk factor for 30-day mortality (OR, 2.82; 95% CI, 1.87-4.24). The adjusted association between thrombocytopenia and death remained similar among the 917 patients with monomicrobial bacteremia (OR, 2.88; 95% CI, 1.83-4.53) and the 945 patients who did not die within the first 48 hours (OR, 2.88; 95% CI, 1.87-4.45.).ConclusionWe observed a strong association between thrombocytopenia at sepsis onset and all-cause mortality in S aureus bacteremia, possibly related to mechanisms other than sepsis alone.

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.

Dataset Information

Prognostic Power of Pathogen Cell-Free DNA in Staphylococcus aureus Bacteremia.

Publications

Prognostic Power of Pathogen Cell-Free DNA in <i>Staphylococcus aureus</i> Bacteremia.

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