be pathogenic when detected in a blood culture, while others are more likely to represent contamination with skin flora; but even common skin organisms such as coagulase-negative staphylococci can cause bloodstream infections under certain conditions. When such organisms are present, interpretation of the culture result involves taking into account the person's clinical condition and whether or not multiple cultures are positive for the same organism. False negatives may be caused by drawing blood cultures after the person has received antibiotics or collecting an insufficient amount of blood. The volume of blood drawn is considered the most important variable in ensuring that pathogens are detected: the more blood that is collected, the more pathogens are recovered. However, if the amount of blood collected far exceeds the recommended volume, bacterial growth may be inhibited by natural inhibitors present in the blood and an inadequate amount of growth medium in the bottle. Over-filling of blood culture bottles may also contribute to iatrogenic anemia. Not all pathogens are easily detected by conventional blood culture methods. Particularly fastidious organisms, such as Brucella and Mycobacterium species, may require prolonged incubation times or special culture media. Some organisms are exceedingly difficult to culture or do not grow in culture at all, so serology testing or molecular methods such as PCR are preferred if infection with these organisms is suspected. History Early blood culture methods were labour-intensive. One of the first known procedures, published in 1869, recommended that leeches be used to collect blood from the patient. A microbiology textbook from 1911 noted that decontamination of the draw site and equipment could take over an hour, and that due to a lack of effective methods for preserving blood, the cultures would sometimes have to be prepared at the patient's bedside. In addition to subculturing the broth, some protocols specified that the blood be mixed with melted agar and the mixture poured into a petri dish. In 1915, a blood culture collection system consisting of glass vacuum tubes containing glucose broth and an anticoagulant was described. Robert James Valentine Pulvertaft published a seminal work on blood cultures in 1930, specifying—among other insights—an optimal blood-to-broth ratio of 1:5, which is still accepted today. The use of SPS as an anticoagulant and preservative was introduced in the 1930s and 40s and resolved some of the logistical issues with earlier methods. From the 1940s through the 1980s, a great deal of research