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Publication Briefs

Study Shows Shortening the Time-to-Antibiotics for Sepsis is Not Associated with an Increase in Antimicrobial Use

Worldwide, sepsis contributes to 50 million hospitalizations and 10 million deaths each year. Practice guidelines recommend prompt treatment for sepsis because delays in antimicrobial therapy are associated with increased mortality. Given the global burden of sepsis, the urgency placed on rapid treatment, and the increasing threat of antimicrobial resistance, empiric data on the trade-offs of accelerating time to treatment for sepsis are critical. This observational cohort study sought to determine whether hospital-level declines in time-to-treatment for sepsis were associated with increases in antimicrobial use, days of therapy, or broadness of coverage among the larger population of patients at-risk for sepsis. Investigators identified 1,559,523 patients – hospitalized at 152 VA and Kaiser Permanente hospitals in northern California from 2013 through 2018 – who were at risk for sepsis. [Patients were admitted through the emergency department with ≥2 systemic inflammatory response criteria (SIRS).] Of these, 273,255 (18%) met objective criteria for sepsis. The primary measure was time to first antimicrobial – calculated as the time from emergency department arrival to first antimicrobial administration. Antimicrobial outcomes included antimicrobial use, days of therapy, and broadness of antibacterial coverage. Clinical outcomes included in-hospital mortality, 30-day mortality, and new culture positivity for a multi-drug resistant (MDR) pathogen.


  • From 2013 through 2018, the median time to antibiotics for sepsis declined by 37 minutes.
  • During the same period, antimicrobial stewardship for patients at risk for sepsis improved, as evidenced by decreasing antimicrobial use, decreasing mean days of antimicrobial therapy, and decreasing use of broad-spectrum antibiotics. Mortality and MDR culture positivity also decreased.
  • Hospital-specific trends were consistent with cohort-wide trends; the vast majority of hospitals accelerated sepsis care and reduced antibiotic use simultaneously.


  • VA hospitals have been able to “thread the needle,” simultaneously improving sepsis care and antimicrobial stewardship.
  • Widespread concerns that accelerating time-to-treatment for sepsis will drive antibiotic misuse or impair antimicrobial stewardship were not borne out in this study cohort.


  • These data apply to VA and Kaiser Permanente in northern California, but may not generalize to other systems that implemented rapid-antibiotics-for-sepsis programs without the same education, antibiotic stewardship, and quality improvement infrastructure.

This study was partly funded by HSR&D (IIR 20-313). Drs. Prescott and Seelye, and Ms. Wang are part of HSR&D’s Center for Clinical Management Research.

Prescott H, Seelye S, Wang XQ, et al. Temporal Trends in Antimicrobial Prescribing During Hospitalization for Potential Infection and Sepsis. JAMA Internal Medicine. June 27, 2022; online ahead of print.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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