Delays in antibiotic redosing: Association with inpatient mortality and risk factors for delay

Although timely administration of antibiotics has an established benefit in serious bacterial infection, the majority of studies evaluating antibiotic delay focus only on the first dose. Recent evidence suggests that delays in redosing may also be associated with worse clinical outcome. In light of the increasing burden of boarding in Emergency Departments (ED) and subsequent need to redose antibiotic in the ED, we examined the association between delayed second antibiotic dose administration and mortality among patients admitted from the ED with a broad array of infections and characterized risk factors associated with delayed second dose administration.

We performed a retrospective cohort study of patients admitted through five EDs in a single healthcare system from 1/2018 through 12/2018. Our study included all patients, aged 18 years or older, who received two intravenous antibiotic doses within a 30-h period, with the first dose administered in the ED. Patients with end stage renal disease, cirrhosis and extremes of weight were excluded due to a lack of consensus on antibiotic dosing intervals for these populations. Delay was defined as administration of the second dose at a time-point greater than 125% of the recommended interval. The primary outcome was in-hospital mortality.

A total of 5605 second antibiotic doses, occurring during 4904 visits, met study criteria. Delayed administration of the second dose occurred during 21.1% of visits. After adjustment for patient characteristics, delayed second dose administration was associated with increased odds of in-hospital mortality (OR 1.50, 95%CI 1.05-2.13). Regarding risk factors for delay, every one-hour increase in allowable compliance time was associated with a 18% decrease in odds of delay (OR 0.82 95%CI 0.75-0.88). Other risk factors for delay included ED boarding more than 4 h (OR 1.47, 95%CI 1.27-1.71) or a high acuity presentation as defined by emergency severity index (ESI) (OR 1.54, 95%CI 1.30-1.81 for ESI 1-2 versus 3-5).

Delays in second antibiotic dose administration were frequent in the ED and early hospital course, and were associated with increased odds of in-hospital mortality. Several risk factors associated with delays in second dose administration, including ED boarding, were identified.