Pathogen-Negative Sepsis Is a Strong Candidate for Stewardship

As physicians and health care organizations search for better ways to curb the use of antibiotics and the growth of antimicrobial resistance, a new study suggests sepsis is one area that might be ripe for better antimicrobial stewardship.

Specifically, the study argues pathogen-negative cases of sepsis, where the current antibiotic treatment time ranges from 4 to 9 days, are a good opportunity that warrants attention. The study was published in Open Forum Infectious Diseases.

Marin H. Kollef, MD, of the Washington University School of Medicine, in St. Louis, writes with colleagues that sepsis represents the most common reason for empiric antibiotic use among patients in American hospitals. Indeed, new guidelines recommend the quick and aggressive use of broad-spectrum antibiotics in patients suspected of having sepsis. Yet, Kollef and colleagues note nearly 9 in 10 cases of sepsis are pathogen-negative cases.

“The large percentage of pathogen-negative patients with sepsis and recent calls to treat such patients within 1 hour of presentation suggest that more patients with pathogen-negative sepsis will receive empiric antibiotic therapy,” they write.

In light of that probability, Kollef and colleagues sought to get a better picture of the data surrounding pathogen-negative sepsis, in hopes of providing better clarity and a pathway toward successful antimicrobial stewardship.

To do so, they looked at 8 years of data (2010 through 2017) from Barnes-Jewish Hospital, in St. Louis. The study included patients who were consecutively hospitalized with sepsis and were 18 years of age or older, had an ICD-9 or ICD-10 classification of severe sepsis or septic shock, and were suffering from their first case of sepsis. This translated to a total of 1486 patients with pathogen-negative sepsis, of whom 1047 survived.

Patients were divided into 3 groups based on duration of treatment: those receiving 3 or fewer days of antibiotics, those receiving 4-7 days, and those receiving more than 7 days of treatment. The median duration of treatment was 6 days.

Patients with more severe cases or higher Charlson Comorbidity Index scores tended to have longer durations of treatment, as did those on mechanical ventilation.

Those who had a specifically documented site of infection also tended to get longer treatment with antibiotics, compared to those without.

Pathogen-negative sepsis cases can be a thorny situation for physicians and hospitals, since a 2016 study found these patients are more likely than pathogen-positive sepsis patients to die. It’s unclear exactly why that’s true, but the authors of the 2016 study say it may have to do with the severity of the illness or with problems in the time of antibiotic administration (either too delayed or too short).

Kollef and colleagues say the clearest factor in sepsis mortality is severity of illness, something that may or may not be affected by antibiotics.

“These observations emphasize the importance of discerning the impact of host factors and disease severity on patient outcomes, which may not be modifiable by antimicrobial therapy,” they write.

In conclusion, Kollef and colleagues say the success of antimicrobial stewardship in other therapeutic areas and the data they have uncovered related to pathogen-negative sepsis therapy suggest a good opportunity for hospitals to re-evaluate their empiric use of antibiotics in these cases.

“Given the outcome benefits observed with the combined use of molecular rapid diagnostic testing and antimicrobial stewardship programs, similar approaches in individuals with pathogen-negative sepsis should be considered regardless of their severity of illness,” they write.