By Ethan Covey
When to administer antimicrobials to patients with sepsis or septic shock is a major clinical decision, and existing evidence is clear—the sooner, the better.
During a session at the 2025 ESCMID Global Congress, in Vienna, experts explored the evidence, challenges and clinical realities behind this decision.
“There is just one aim—early risk assessment,” said Evangelos Giamarellos-Bourboulis, MD, PhD, a professor of internal medicine and infectious diseases at the National and Kapodistrian University of Athens Medical School, in Greece, and the president of the European Sepsis Alliance. “Early means before clinical signs of risk appear, sometimes before the patient looks sick, when all you have is a biomarker increase.”
Highlighting results from a landmark 2006 study by Kumar et al (Crit Care Med 2006;34[6]:1589-1596), Dr. Giamarellos-Bourboulis emphasized the steep decline in survival associated with each hour of delay once hypotension begins.
“If antibiotics reach the veins within the first hour, the chance of survival is 80%,” he said. “Every hour of delay decreases that chance by 7.6%.”
However, real-world logistical challenges faced in hospitals can stretch those delays into hours.
In New York state, a 2017 mandate requiring hospitals to report sepsis care metrics quality improvement yielded significant data regarding how patients with sepsis and septic shock are treated—and highlighted wide institutional variation. The data set of nearly 50,000 patients revealed that some hospitals administered antimicrobials within three hours in more than 90% of cases, while others reached only 60% or 70%.
“From the patient perspective, which hospital would you rather be treated at if you were presenting with sepsis or septic shock?” asked Laura Evans, MD, a professor, Division of Pulmonary, Critical Care, and Sleep Medicine, and the medical director of critical care at the University of Washington Medical Center, in Seattle.
Both speakers highlighted that newer evidence continues to reinforce the time-dependent effect.
Dr. Evans presented findings from the ONE-BED trial (Eur J Emerg Med 2025;32[2]:109-115), a cluster-randomized study of emergency departments in France and Spain. Among patients who died, the median time to antibiotics was 95 minutes, compared with just less than one hour for survivors.
“There are very few things in critical care where we see such a clear dose–response relationship,” Dr. Evans said. “Time to antibiotics in sepsis is one of them.”
Not So Fast
However, both presenters also acknowledged the challenge and complexity of real-world decision-making in a busy hospital.
“Patients don’t come into the hospital wearing a big sign that says, ‘I have septic shock,’” Dr. Evans noted. Diagnostic uncertainty often complicates decisions, particularly when patients are not in overt shock. In these cases, the Surviving Sepsis Campaign guidelines encourage balancing illness severity with certainty of infection. No one wants to give unnecessary or incorrect antibiotics.
“If my patient is sick and there is a possibility this is due to infection, I would advocate that those patients should get antimicrobials as soon as possible,” Dr. Evans said. “Sepsis is very unforgiving.”
Dr. Giamarellos-Bourboulis underscored the role of risk stratification tools, such as qSOFA (quick Sequential Organ Failure Assessment) score and NEWS2 (National Early Warning Score 2), both used to evaluate whether a person is at risk for sepsis, and emerging biomarkers in narrowing uncertainty.
While the tension between rapid treatment and antimicrobial stewardship demands important consideration, Dr. Evans stressed that timeliness must take priority when patients are critically ill.
“I don’t think that a single dose or a couple of doses [of antibiotic] while you are developing more certainty about infection is going to fundamentally change your antimicrobial resistance environment,” she said.
Both experts concluded by stressing the importance of one message: Act early.
“Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately,” Dr. Evans said. Dr. Giamarellos-Bourboulis agreed: “Act early. Early drug treatment is the only way to cure or improve your patient and avoid organ dysfunction,” he said.
Dr. Evans reported that she has received honoraria from the American Board of Internal Medicine. Dr. Giamarellos-Bourboulis reported that he has received honoraria from Abbott Products Operations AG, bioMérieux (France), Brahms, Swedish Orphan Biovitrum, and Thermo Fisher Scientific GmbH (Germany); and consultation fees paid to the University of Athens from Abbott Products Operations AG, Abionic SA, Bio-Rad and Swedish Orphan Biovitrum.
