Timing of Antibiotic Treatment in Severe Sepsis, Revisited

Summary and Comment |
August 26, 2014

Timing of Antibiotic Treatment in Severe Sepsis, Revisited

  1. Thomas Glück, MD

Data from the Surviving Sepsis Campaign database suggest that initiating antibiotic therapy within 1 hour after diagnosis of severe sepsis or septic shock lowers mortality.

  1. Thomas Glück, MD

Numerous studies have shown that prompt administration of appropriate antibiotic therapy (i.e., within the first hour of documented hypotension) is a key measure in treating patients with sepsis (NEJM JW Infect Dis Jun 22 2006). Using data for January 2005 through February 2010 from the Surviving Sepsis Campaign database, researchers readdressed the time-criticality of antibiotic treatment in severe sepsis and septic shock.

Of 28,150 cases identified from 165 intensive care units (ICUs) worldwide, 17,990 with data on antibiotic administration and without antimicrobial treatment before sepsis onset were included in the analysis. In-hospital mortality in this cohort was 31.3% overall — 32.0% in patients who received antibiotics within the first hour, dropping to 28.1% in individuals treated during the second hour, and then steadily increasing to 39.6% in those with a >6-hour treatment delay. Patients treated within the first hour and those with treatment delays >6 hours tended to be sicker, with higher sepsis-severity scores and rates of multi-organ failure, and were more likely to have nosocomial infection.

Logistic regression analysis adjusted for sepsis-severity score, ICU admission source, and geographic region showed a steady increase in mortality risk, from 24.6% in patients receiving antibiotics within the first hour to 33.1% in those who had a >6-hour delay, with statistically significant increments after the second hour.


This investigation suggests that antibiotic administration within the first (“golden”) hour of severe sepsis and septic shock reduces mortality, confirming Kumar and colleagues' earlier findings. Results were similar regardless of whether the patients had severe sepsis or septic shock, or whether sepsis was identified on the ward, in the emergency department, or in the ICU.

But how to translate these findings into practice, and — as an editorialist cautions — “avoid a false start striving for gold”? Undertreatment or late antibiotic administration can be caused by underrecognition of sepsis. Repeated education of primary care providers and hospital staff about the various presentations of sepsis and reinforcement of sepsis-treatment algorithms is needed to increase our awareness of sepsis to the levels we already have for myocardial infarction and stroke. Meanwhile, we must avoid liberal use of broad-spectrum antibiotics merely to be “timely” and “appropriate,” which would bring more side effects and aggravate our already serious problem of antibiotic resistance.

Editor Disclosures at Time of Publication

  • Disclosures for Thomas Glück, MD at time of publication Editorial boards Consilium Infectiorum


Reader Comments (4)

MOHAMED KHALAF Physician, Hematology, Maadi hospital Cairo

The concerns of higher c diff infections or antibiotic resistance are reasonable but I think in the high risk immunocompromized groups the benefits of early therapy will outweigh these risks

pramodh karunakaran Physician, Internal Medicine, hospital

Antibiotics with in first hour is a simple but very effective way to reduce the mortality in severe sepsis or septic shock.I would suggest to hit as early as possible after taking specimens for culture.

Thomas J Rush, MD Physician, Infectious Disease

Inevitably this article will and has contributed to the overuse and inappropriate use of broad spectrum antibiotics. The entities called "sepsis" and "severe sepsis" and even "septic shock" are poorly defined and the problem is further aggravated as the age of patients showing up in our emergency rooms is increasing. Many of these patients are poor historians or demented, are hypotensive due to dehydration, are hypothermic for a variety of reasons. Combine this with aggressive ER physicians, a litigious public, government dictated "quality" measurements, families with unrealistic expectations about the life expectancies of their loved ones and the likelihood is that this belief that a life may be saved by prompt administration of antibiotics in the ER in "septic" patients will lead to many more deaths due to C. difficile colitis and infections due to drug resistant antibiotics than are saved by adhering to the one hour rule.



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