Temporal Trends and Hospital Variation in Time-to-Antibiotics Among Veterans Hospitalized With Sepsis

Abstract

Importance: It is unclear whether antimicrobial timing for sepsis has changed outside of performance incentive initiatives.

Objective: To examine temporal trends and variation in time-to-antibiotics for sepsis in the US Department of Veterans Affairs (VA) health care system.

Design, setting, and participants: This observational cohort study included 130 VA hospitals from 2013 to 2018. Participants included all patients admitted to the hospital via the emergency department with sepsis from 2013 to 2018, using a definition adapted from the Centers for Disease Control and Prevention Adult Sepsis Event definition, which requires evidence of suspected infection, acute organ dysfunction, and systemic antimicrobial therapy within 12 hours of presentation. Data were analyzed from October 6, 2020, to July 1, 2021.

Exposures: Time from presentation to antibiotic administration.

Main outcomes and measures: The main outcome was differences in time-to-antibiotics across study periods, hospitals, and patient subgroups defined by presenting temperature and blood pressure. Temporal trends in time-to-antibiotics were measured overall and by subgroups. Hospital-level variation in time-to-antibiotics was quantified after adjusting for differences in patient characteristics using multilevel linear regression models.

Results: A total of 111 385 hospitalizations for sepsis were identified, including 107 547 men (96.6%) men and 3838 women (3.4%) with a median (interquartile range [IQR]) age of 68 (62-77) years. A total of 7574 patients (6.8%) died in the hospital, and 13 855 patients (12.4%) died within 30 days. Median (IQR) time-to-antibiotics was 3.9 (2.4-6.5) hours but differed by presenting characteristics. Unadjusted median (IQR) time-to-antibiotics decreased over time, from 4.5 (2.7-7.1) hours during 2013 to 2014 to 3.5 (2.2-5.9) hours during 2017 to 2018 (P < .001). In multilevel models adjusted for patient characteristics, median time-to-antibiotics declined by 9.0 (95% CI, 8.8-9.2) minutes per calendar year. Temporal trends in time-to-antibiotics were similar across patient subgroups, but hospitals with faster baseline time-to-antibiotics had less change over time, with hospitals in the slowest tertile decreasing time-to-antibiotics by 16.6 minutes (23.1%) per year, while hospitals in the fastest tertile decreased time-to-antibiotics by 7.2 minutes (13.1%) per year. In the most recent years (2017-2018), median time-to-antibiotics ranged from 3.1 to 6.7 hours across hospitals (after adjustment for patient characteristics), 6.8% of variation in time-to-antibiotics was explained at the hospital level, and odds of receiving antibiotics within 3 hours increased by 65% (95% CI, 56%-77%) for the median patient if moving to a hospital with faster time-to-antibiotics.

Conclusions and relevance: This cohort study across nationwide VA hospitals found that time-to-antibiotics for sepsis has declined over time. However, there remains significant variability in time-to-antibiotics not explained by patient characteristics, suggesting potential unwarranted practice variation in sepsis treatment. Efforts to further accelerate time-to-antibiotics must be weighed against risks of overtreatment.

Figure 1.. Time to First Antibiotic Administration by Study Period and by Patient Subgroups Over Time

Patient subgroups were defined by presenting temperature and blood pressure measured during the 25 hours surrounding emergency department presentation (24 hours before arrival to 1 hour after arrival). Specifically, patients were classified as normothermic (≥36 °C and ≤38 °C), hypothermic (<36 °C), or hyperthermic (>38 °C) and as hypotensive (systolic blood pressure <90 mm Hg) or normotensive (≥90 mm Hg). Circles indicate median time-to-antibiotics.

Figure 2.. Temporal Trends in Time-to-Antibiotics Among Hospitals With the Largest, Middle, and Least Decline in Time-to-Antibiotics From 2013 to 2018

Tertile 1 declined by a median 19.1 minutes per year (44 hospitals); tertile 2 declined by a median of 10.1 minutes per year (43 hospitals); tertile 3 declined by a median 2.8 minutes per year (43 hospitals). Orange dots indicate median time-to-antibiotics per year; blue lines, time-to-antibiotics per individual hospital.

Figure 3.. Variation in Median Time-to-Antibiotics by Hospital from 2013 to 2018

Individual hospitals are ordered from fastest to slowest time-to-antibiotics. The median time-to-antibiotics for each individual hospital is presented as a blue dot with corresponding 95% CIs (whiskers). The blue dotted line indicates the overall median time-to-antibiotic. The model intraclass correlation is 0.075 for 2013 to 2014, 0.081 for 2015 to 2016, and 0.068 for 2017 to 2018.