Sampling theory for molecular-and blood culture-based techniques: Significance and impact for future point-of-care pathogen detection

Nam Tran, Terry Keith Brock, Daniel Mecozzi

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Septicemia is associated with high mortality. Inadequate antimicrobial therapy leads to poor outcomes. Pathogen detection aids in clinical decision making by directing appropriate treatment. Sampling volume and in vivo microbial blood concentration affect analytical sensitivity and represent a significant design challenge for future point-of-care pathogen detection technologies. METHODS: We applied the Poisson distribution to identify the probability of collecting no pathogens from a given sampling volume and bloodstream pathogen concentration for existing blood culture and whole-blood polymerase chain reaction (PCR) pathogen detection technologies. The concept of "effective target pathogen concentration" is introduced to account for the unique detection of both cell-free and intracellular DNA by PCR methods. RESULTS: The probability for a 10-mL blood culture or a 1.5-mL PCR specimen not collecting pathogens was 4.54 × 10-5 and 0.22, respectively, when pathogen bloodstream concentrations were at 1 colony-forming unit/mL. The probability of collecting no pathogens decreased as pathogen bloodstream concentrations increased. Accounting cell-free target pathogen DNA, the PCR sampling probability substantially improved and exceeded blood culture performance. CONCLUSIONS: The probability of not isolating pathogens from a PCR or blood culture specimen was highly dependent on sampling volume and pathogen concentration. Cell-free pathogen DNA enhances PCR performance despite smaller sampling volumes. The impact of sampling volume and target pathogen concentrations should be considered when developing point-of-care pathogen detection solutions that may be constrained to smaller sampling volumes. Further in vitro studies are warranted to validate this theory during dynamic sepsis conditions.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalPoint of Care
Issue number1
StatePublished - Mar 2013


  • binomial distribution
  • bloodstream infection
  • cell-free DNA
  • colony-forming units
  • DNAemia
  • limit of detection
  • Poisson distribution
  • septicemia

ASJC Scopus subject areas

  • Nursing(all)


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