Investigating the time to blood culture positivity: why does it take so long?

Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time. Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections. However, the time to blood culture positivity can be lengthy. Underpinning this is the reliance on bacteria replicating to a high concentration, which is necessary for the detection using routine blood culture systems. To improve the diagnosis and management of patients with BSIs, more sensitive detection methods are required. The study aimed to answer key questions addressing the delay in BSI detection and whether the time to BSI detection could be expedited using a Scattered Light Integrated Collection (SLIC) device. A proof-of-concept study was conducted to compare the time to positivity (TTP) of Gram-negative BCs flagging positive on BacT/ALERT with an SLIC device. An SLIC device was utilized to compare the TTP of the most prevalent BSI pathogens derived from nutrient broth and BC, the influence of bacterial load on TTP and the TTP directly from whole blood. Additionally, the overall turnaround time (TAT) of SLIC was compared with that of a standard hospital workflow. Most pathogens tested took significantly longer to replicate when derived from BC than from nutrient medium. The median TTP of Gram-negative BC on BacT/ALERT was 13.56 h with a median bacterial load of 6.4×10 c.f.u. ml. All pathogens (7/7) derived from BC at a concentration of 10 c.f.u. ml were detectable in under 70 min on SLIC. Decreasing BC concentration from 10 to 10 c.f.u. ml increased the TTP of SLIC from 15 to 85 min. Direct BSI detection from whole blood on SLIC demonstrated a 76% reduction in TAT when compared with the standard hospital workflow. An SLIC device significantly reduced the TTP of common BSI pathogens. The application of this technology could have a major impact on the detection and management of BSI.