Pathogen enrichment from human whole blood for the diagnosis of bloodstream infection: Prospects and limitations.

Blood culture represents the current reference method for the detection of bacteria or fungi in the circulation. To accelerate pathogen identification, molecular diagnostic methods, mainly based on polymerase chain reaction (PCR), have been introduced to ensure early and targeted antibiotic treatment of patients suffering from bloodstream infection. Still, these approaches suffer from a lack of sensitivity and from inhibition of PCR in a number of clinical samples, leading to false negative results. To overcome these limitations, various approaches aiming at the enrichment of pathogens from larger blood volumes prior to the extraction of pathogen DNA, thereby also depleting factors interfering with PCR, have been developed. Here, we provide an overview of current systems for diagnosing bloodstream infection, with a focus on approaches for pre-analytical pathogen enrichment, and highlight emerging applications of pathogen depletion for therapeutic purposes as a potential adjunctive treatment of sepsis patients.