7 Days of Antibiotics as Effective as 14 for BSI

LOS ANGELES — A 7-day antibiotic course for treating hospitalized patients’ bloodstream infection (BSI) was just as effective as a 14-day course, according to new data from a seven-country noninferiority trial. The findings from the Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial has implications for healthcare costs and antibiotic harm reduction globally and could potentially reduce antimicrobial resistance.

This was the largest randomized trial for patients with BSI, with more than 3600 patients, Nick Daneman, MD, MSc, clinician scientist in the Division of Infectious Diseases at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, said at the Infectious Disease Week (IDWeek) 2024 Annual Meeting. Daneman is co-lead investigator with Robert Fowler, MD, with the Interdepartmental Division of Critical Care Medicine, also from the Sunnybrook center.

The trial grew to include patients at 74 hospitals in Australia, Canada, Israel, New Zealand, Saudi Arabia, Switzerland, and the United States.

Patients had a range of underlying causes of their BSI, most commonly urinary tract, lung, and abdominal infections, Daneman said.

BSIs are very common and very lethal, Daneman noted, with 600,000 cases per year and 90,000 deaths per year in North America alone. “We need more evidence on how to optimally treat these patients.”

As part of the trial, the investigators reviewed the literature on typical antibiotic courses globally and found the most common duration was 14 days, Daneman said. Before BALANCE, there had been no randomized trials, he explained.

They randomized 3631 patients 1:1 to either 7 or 14 days with a primary endpoint of 90-day mortality. More than half of the patients were critically ill and were admitted to an intensive care unit (ICU) at the time of the study, Daneman said.

In the 7-day treatment arm, 14.5% patients died within 90 days. In the 14-day treatment arm, 16.1% patients died within 90 days.

“We also found that getting 7-day treatment up front led to less total antibiotic use in follow-up and shorter lengths of stay in the hospital,” Daneman said. Additionally, in secondary results, the team found that the 7-day treatment was as effective as 14 in a range of other outcomes, including ICU mortality, hospital mortality, relapse of BSI, and other markers.

Practice-Changing Results

“We can say really clearly here that 7 days is noninferior in the treatment of bloodstream infections,” he said, adding that 7-day treatments should be the general strategy for BSIs going forward.

“This is a very strong late-breaker abstract that may change clinical practice,” said Yohei Doi, MD, PhD, professor of medicine in the Division of Infectious Diseases at University of Pittsburgh in Pittsburgh, who was not part of the study.

The results of the BALANCE trial have been much anticipated, he said, as they help answer a key question in BSI.

“There’s no consensus on how long to treat,” Doi said in an interview. “When I was in training, we were all told 2 weeks (of antibiotics) for bacteremia. That has become shorter over time, with mostly retrospective data suggesting that maybe shorter treatment duration is as safe and effective as longer duration. The definitive answer only comes when patients are randomly assigned” as they were in this study.

Current guidelines don’t specify an antibiotic duration for bacteremia, per se, Doi said, because bacteremia is usually a secondary condition — a urinary tract infection that spills over into the bloodstream, for instance, he said.

The strengths include the size of the study and it’s seven-country scope, Doi said, and the “extremely tight” noninferiority margin of only 4% that adds more confidence in the results. For comparison, he said, a noninferiority margin for a new drug seeking FDA approval “typically could be anywhere from 7.5% to as much as 15%.”

Few Exclusion Criteria

Doi highlighted that this trial also had few exclusion criteria. Those excluded had extreme immunosuppression, such as people who had undergone transplant and those who have neutropenia or an undrained abscess, for instance, he noted. They included ICU and non-ICU patients, gram-negative and gram-positive pathogens, and included patients with conditions such as renal failure. Patients with Staphylococcus aureus were excluded because of the inherent extended treatment times.

Their careful selection of exclusion criteria is important, Doi said, because “we want the data to be applicable to patients we see every day.”

Daneman said the team has already launched BALANCE plus, a platform trial for patients with gram-negative BSIs to answer further treatment questions.

Daneman and Doi reported no relevant financial relationships.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, Northwestern magazine, and Nurse.com and was an editor at the Chicago Sun-Times, The Cincinnati Enquirer, and St. Cloud Times. Follow her on X: @MLfrellick