High <i>nuc</i> DNA load in whole blood is associated with sepsis, mortality and immune dysregulation in <i>Staphylococcus aureus</i> bacteraemia

Ziegler, Ingrid; Cajander, Sara; Rasmussen, Gunlög; Ennefors, Theresa; Mölling, Paula; Strålin, Kristoffer

doi:10.1080/23744235.2018.1562205

Cited by 26 publications

(27 citation statements)

References 43 publications

(54 reference statements)

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“…Higher mortality in bacteremic sepsis and in non-bacteremic sepsis with prior antibiotic treatment can also be indicative of bacterial load in blood being associated with sepsis severity, which previously has been demonstrated for isolated pathogens 35 – 38 .…”

Section: Discussionmentioning

confidence: 73%

Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching

Mellhammar

Kahn

Whitlow

et al. 2021

Sci Rep

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One can falsely assume that it is well known that bacteremia is associated with higher mortality in sepsis. Only a handful of studies specifically focus on the comparison of culture-negative and culture-positive sepsis with different conclusions depending on study design. The aim of this study was to describe outcome for critically ill patients with either culture-positive or -negative sepsis in a clinical review. We also aimed to identify subphenotypes of sepsis with culture status included as candidate clinical variables. Out of 784 patients treated in intensive care with a sepsis diagnosis, blood cultures were missing in 140 excluded patients and 95 excluded patients did not fulfill a sepsis diagnosis. Of 549 included patients, 295 (54%) had bacteremia, 90 (16%) were non-bacteremic but with relevant pathogens detected and in 164 (30%) no relevant pathogen was detected. After adjusting for confounders, 90-day mortality was higher in bacteremic patients, 47%, than in non-bacteremic patients, 36%, p = 0.04. We identified 8 subphenotypes, with different mortality rates, where pathogen detection in microbial samples were important for subphenotype distinction and outcome. In conclusion, bacteremic patients had higher mortality than their non-bacteremic counter-parts and bacteremia is more common in sepsis when studied in a clinical review. For reducing population heterogeneity and improve the outcome of trials and treatment for sepsis, distinction of subphenotypes might be useful and pathogen detection an important factor.

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Section: Discussionmentioning

confidence: 73%

Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching

Mellhammar

Kahn

Whitlow

et al. 2021

Sci Rep

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“…aureus species-specific ddPCR have recently been published in a separate article focusing on nuc DNA loads in S . aureus bacteremia [32].…”

Section: Resultsmentioning

confidence: 99%

16S rDNA droplet digital PCR for monitoring bacterial DNAemia in bloodstream infections

Ziegler

Lindström

Källgren³

et al. 2019

PLoS ONE

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Repeated quantitative measurement of bacterial DNA on whole blood has been shown to be a promising method for monitoring bloodstream infection (BSI) with selected bacterial species. To enable broad use of this method, we developed a quantitative droplet digital PCR (ddPCR) method for 16S rDNA. It was validated with species-specific ddPCRs for Staphylococcus aureus (nuc), Streptococcus pneumoniae (lytA), and Escherichia coli (uidA) on spiked whole blood samples and on repeated whole blood samples (days 0, 1–2, 3–4, 6–8, and 13–15) from 83 patients with BSI with these pathogens. In these patients, 16S rDNA and species-specific DNA were detected in 60% and 61%, respectively, at least at one time-point. The highest positivity rates were seen in S. aureus BSI, where 92% of the patients were 16S rDNA-positive and 85% nuc-positive. Quantitative 16S rDNA and species-specific DNA showed strong correlations in spiked samples (r = 0.98; p < 0.0001) and clinical samples (r = 0.84; p < 0.0001). Positivity for 16S rDNA was rapidly cleared in patients with S. pneumoniae and E. coli BSI, but more slowly and sometimes persisted, in those with S. aureus BSI. The initial 16S rDNA load was higher in BSI patients with sepsis (Sepsis-3 definition) than without sepsis (median 2.38 vs. 0 lg10 copies/mL; p = 0.031) and in non-survivors than in survivors (median 2.83 vs. 0 lg10 copies/mL; p = 0.006). 16S rDNA ddPCR appears to be a promising method for bacterial DNA monitoring during BSI. The clinical value of such monitoring should be further studied.

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Section: Discussionmentioning

confidence: 72%

Higher mortality in bacteremic sepsis - A propensity score matched study

Mellhammar

Kahn

Whitlow

et al. 2020

Preprint

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The aim of this study was to describe outcome for critically ill patients with either culture-positive or -negative sepsis.In a clinical chart review of patients with a sepsis diagnosis treated in an intensive Care Unit (ICU), those who fulfilled sepsis-3 criteria and at had least one blood culture sampled ±48h from ICU admission were included. In a propensity score analysis bacteremic and non-bacteremic patients were matched with regard to age, comorbidities, site of infection and antimicrobial therapy prior to blood cultures.Out of 784 patients treated in the ICU with a sepsis diagnosis, blood cultures were missing in 140 excluded patients and additionally 95 excluded patients did not fulfill a sepsis diagnosis. In total 549 patients were included, 295 (54%) with bacteremia, 90 (16%) were non-bacteremic but had relevant pathogens detected from another body location and in 164 (30%) no relevant pathogen was detected in microbial samples. After the propensity score analysis, 90-day mortality was higher in bacteremic patients, 47%, than in non-bacteremic patients, 36%, p =0.04. In conclusion, bacteremic patients had higher mortality than their non-bacteremic counter-parts and bacteremia is more common in sepsis when studied in a clinical review.

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High nuc DNA load in whole blood is associated with sepsis, mortality and immune dysregulation in Staphylococcus aureus bacteraemia

Cited by 26 publications

References 43 publications

Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching

Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching

16S rDNA droplet digital PCR for monitoring bacterial DNAemia in bloodstream infections

Higher mortality in bacteremic sepsis - A propensity score matched study

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