Just over one-third of sepsis patients have positive blood cultures, mainly due to inadequate sampling volumes (50% of adults have < 1.0 CFU/mL blood) and the prior use of antibiotics. However, 20-30% of sepsis patients are given inappropriate empirical antibiotics. The Clinical and Laboratory Standards Institute guidelines recommend paired culture sets to help discriminate between contaminant organisms and true pathogens; four 10-mL bottles (2 sets) should be used for the initial evaluation to detect about 90-95% of bacteremias and six 10-mL bottles (3 sets) should be used to detect about 95-99% of bacteremias. It has also been shown that the positivity rate increased by 15-35% with resin-based media in patients on antibiotics. For diagnosing catheter-related bloodstream infections, differential time-to-positivity is one method recommended to help determine whether the catheter is truly the source of infection. The proper training of personnel with regard to drawing an appropriate blood volume and the importance of clear labeling of culture bottles is also of critical importance. Furthermore, if the contamination rate is relatively high, hiring dedicated staff who are well-trained in order to get a lower blood culture contamination rate may be cost-effective. It is because high false-positive blood culture rates due to contamination are associated with significantly increased hospital and laboratory charges.