The modern concept of sepsis has focused on the human response to invading organisms. In 1991, a North American consensus conference introduced the idea that sepsis is the host’s inflammatory response to in fection. 1 For simplicity, the systemic inflammatory re sponse syndrome (SIRS) was defined by four variables: temperature, heart rate, respiratory rate, and white blood cell count. Only minor abnormalities in these variables are needed for a patient to meet the SIRS criteria. These simple clinical criteria allowed researchers to identify patients to enrol in sepsis trials and were rapidly adopted. However, the SIRS approach has three major problems. First, the SIRS criteria are so sensitive that up to 90% of patients admitted to an intensive care unit (ICU) meet the criteria. 2, 3

SIRS can be caused by many non-infectious clinical processes, such as severe trauma, burns, pancreatitis, and ischaemic reperfusion events. If sepsis is defined by the presence of SIRS criteria plus an infection, and almost every acutely ill patient meets the SIRS criteria, then sepsis effectively equals infection. But, although all patients with sepsis have an infection, the reverse is not necessarily true—ie, not all patients with an infection have sepsis. Second, some degree of host response is actually inherent to the infection; indeed, this is an important component of the difference between infection and mere colonisation. Almost any infection—even a minor viral illness—is typically asso ciated with fever and accompanying changes, including tachycardia, some hyperventilation, and an increased white cell count. This host response has beneficial aspects, and a reduced or absent reaction could suggest that the individual is immunocompromised. Third, deciphering the role of