Antibiotics: it is all about timing, isn’t it?

Sepsis guidelines and quality measures set aggressive deadlines for administering antibiotics to patients with possible sepsis or septic shock. However, the diagnosis of sepsis is often uncertain, particularly upon initial presentation, and pressure to treat more rapidly may harm some patients by exposing them to unnecessary or inappropriate broad-spectrum antibiotics.Observational studies that report that each hour until antibiotics increases mortality often fail to adequately adjust for comorbidities and severity of illness, fail to account for antibiotics given to uninfected patients, and inappropriately blend the effects of long delays with short delays. Accounting for these factors weakens or eliminates the association between time-to-antibiotics and mortality, especially for patients without shock. These findings are underscored by analyses of the Centers for Medicaid and Medicare Services SEP-1 measure: it has increased sepsis diagnoses and broad-spectrum antibiotic use but has not improved outcomes.Clinicians are advised to tailor the urgency of antibiotics to their certainty of infection and patients' severity of illness. Immediate antibiotics are warranted for patients with possible septic shock or high likelihood of infection. Antibiotics can safely be withheld to allow for more investigation, however, in most patients with less severe illnesses if the diagnosis of infection is uncertain.