Patients with metastatic cancer, shock benefit from earlier sepsis antibiotics

Key takeaways:

• The 30-day mortality benefit of sepsis antibiotic treatment within 3 hours was larger in some patient characteristic groups.
• This outcome was found in Poisson regression and two additional analyses.

With earlier receipt of antibiotics for sepsis, those with vs. without metastatic cancer or shock had larger reductions in 30-day mortality, according to results published in American Journal of Respiratory and Critical Care Medicine.

Rachel K. Hechtman

“Our findings support the current Surviving Sepsis Campaign recommendations to prioritize rapid administration of antibiotics for patients with possible sepsis and shock,” Rachel K. Hechtman, MD, pulmonary and critical care fellow at the University of Michigan, told Healio. “Our findings also support consideration of other characteristics that could indicate a patient may have greater benefit from earlier antibiotics.”

Practically speaking, Hechtman continued, this means that clinicians may use characteristics in addition to the presence of shock to decide whether to provide antibiotics earlier when there is diagnostic uncertainty.

“If our findings are verified by future studies, they would suggest, for instance, that a younger patient with metastatic cancer and acute liver dysfunction could have greater benefit from earlier antibiotics,” Hechtman said. “Therefore, a clinician may decide to give such a patient antibiotics before they are certain the patient has sepsis.”

In a multicenter, observational cohort study, Hechtman and colleagues analyzed 273,255 patients (median age, 69 years; 78.9% men) hospitalized with community-onset sepsis who received antibiotics by hour 12 to determine whether certain patients benefit more from earlier antibiotic treatment in terms of 30-day mortality.

Nearly half (48%; median age, 70 years) of the total cohort was treated with antibiotics within 3 hours (median, 1.9 hours), whereas the remaining 52% (median age, 69 years) were treated after the 3-hour mark but no later than the 12-hour mark (median 5.2 hours).

Between the shorter and longer time-to-antibiotic groups, several baseline characteristics significantly differed (P < .001), including the proportion of patients with an elevated respiratory rate (78.2% vs. 67.9%), abnormal temperature (61.9% vs. 53.3%), lactate elevation (67.4% vs. 47.5%), shock (15.1% vs. 10.2%), acute kidney dysfunction (45.5% vs. 56.6%) and acute liver dysfunction (8.1% vs. 13%).

Researchers observed seven patient characteristics in which there was a link between antibiotic treatment within 3 hours and larger decreases in adjusted absolute 30-day mortality via multivariable Poisson regression models:

• shock (with, 7.03%; 95% CI, 5.85%-8.17% vs. without, 2.86%; 95% CI, 2.2%-3.5%);
• acute liver dysfunction (with, 7.05%; 95% CI, 5.78%-8.27% vs. 2.54%; 95% CI, 1.97%-3.09%);
• acute hematologic dysfunction (with, 6.96%; 95% CI, 5.86%-8.03% vs. without, 2.67%; 95% CI, 2.01%-3.32%);
• metastatic cancer (with, 5.03%; 95% CI, 4.28%-5.76% vs. without, 0.41%; 95% CI, 0.22%-0.6%);
• more acute organ dysfunction (≥ 3 dysfunctions, 4.8%; 95% CI, 3.89%-5.68% vs. one dysfunction, 0.54%; 95% CI, 0.28%-0.8%);
• abnormal temperature (1.5%; 95% CI, 1.22%-1.76% vs. normal temperature, 0.79%; 95% CI, 0.44%-1.12%); and
• younger age (aged 50-59 years, 1.9%; 95% CI, 1.42%-2.37% vs. aged 80-89 years, 0.83%; 95% CI, 0.15%-1.49%).

“We had hypothesized that indications of more severe acute illness would be associated with greater benefit from earlier antibiotics, such as shock and multiorgan failure,” Hechtman told Healio. “We did not anticipate finding that an underlying comorbid condition (metastatic cancer) would have an equal if not stronger association with greater benefit from earlier antibiotics.”

A causal forest model further showed more benefit with earlier antibiotic treatment among those with metastatic cancer and shock, and spline analysis demonstrated a nonlinear higher mortality risk with longer time-to-antibiotics, according to researchers.

“Future studies working to understand the impact of time-to-antibiotics on sepsis mortality will need to account for the heterogeneity of benefit,” Hechtman said.

Since the impact of antibiotic timing on sepsis mortality varies significantly by several patient characteristics, she continued, future studies of the effect of time-to-antibiotics in sepsis will need to account for this.

“It will be necessary for further studies to confirm which patient characteristics are reliably associated with greater mortality benefit from earlier antibiotics,” Hechtman added.