High nuc DNA load in whole blood is associated with sepsis, mortality and immune dysregulation in Staphylococcus aureus bacteraemia.
BACKGROUND
Staphylococcus aureus bacteraemia is a disease with varying presentation, ranging from uncomplicated to life-threatening infections. In S. aureus bacteraemia, a high load of bacterial DNA in blood has been linked to mortality. We hypothesized that a high DNA load would also be linked to the presence of sepsis, and to high C-reactive protein (CRP) and lymphopaenia, indicating inflammation and immunosuppression.


METHODS
Twenty-seven patients with culture-proven S. aureus bacteraemia, 13 (48%) with sepsis and six (22%) non-survivors, were enrolled in a prospective study. Blood samples were collected on days 0, 1-2, 3-4, 6-8, 13-15 and 26-30, and subjected to droplet digital PCR targeting the nuc gene to determine the nuc DNA load.


RESULTS
nuc DNA was detected on days 0-2 in 22 patients (81%), and on days 6-8 in three patients (all non-survivors). The nuc DNA load on days 1-2 was significantly elevated in patients with sepsis (median 2.69 versus 1.32 log10 copies/mL; p = .014) and in non-survivors (median 2.5 versus 1.0 log10 copies/mL; p = .033). Patients with a high nuc DNA load (>3.0 log10 copies/mL) on days 1-2 had significantly elevated CRP levels at all timepoints, and significantly decreased lymphocyte counts on days 0, 1-2, 13-15 and 26-30.


CONCLUSIONS
Our results indicate that a high initial load of S. aureus DNA in blood is associated with sepsis, mortality and persistent immune dysregulation in S. aureus bacteraemia patients. Further studies are needed to define the role of bacterial DNA load monitoring in the management of S. aureus bacteraemia.
['Ziegler|Ingrid|I|http://orcid.org/0000-0002-5929-212X', 'Cajander|Sara|S|', 'Rasmussen|Gunlög|G|', 'Ennefors|Theresa|T|', 'Mölling|Paula|P|', 'Strålin|Kristoffer|K|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D016470:Bacteremia D001426:Bacterial Proteins D002097:C-Reactive Protein D004269:DNA, Bacterial D004697:Endocarditis, Bacterial D005260:Female D006801:Humans D008297:Male D008836:Micrococcal Nuclease D008875:Middle Aged D016133:Polymerase Chain Reaction D060888:Real-Time Polymerase Chain Reaction D013203:Staphylococcal Infections D013211:Staphylococcus aureus D055815:Young Adult
DNA load Sepsis bacteraemia Droplet digital PCR PCR Bloodstream infection