7 days of antibiotics as effective as 14 days for bloodstream infections

In the noninferiority BALANCE* trial, 7 days of antibiotic use is as effective as 14 days for treating bloodstream infections (BSIs) in hospitalized patients, drawing renewed interest from clinicians attending IDWeek 2024.

Study lead investigator Dr Nick Daneman from Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, said BSIs are associated with substantial morbidity and mortality worldwide. “Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain,” he added.

Despite advances in antimicrobial drug therapy, intensive care, and prevention strategies, BSIs cause an estimated 250,000 deaths annually in North America and Europe combined. [IDWeek 2024, abstract 376; Clin Microbiol Infect 2013;19:501-509]

“With the magnitude of cases, we need more evidence on how to treat BSI patients optimally,” pointed out Daneman.

BALANCE included 3,631 patients from 74 hospitals in Australia, Canada, Israel, New Zealand, Saudi Arabia, Switzerland, and the US, with underlying causes of bacteraemia. [N Engl J Med 2024;doi:10.1056/NEJMoa2404991]

Bacteraemia most commonly originated from the urinary tract (42.2 percent), abdomen (18.8 percent), lung (13 percent), vascular catheters (6.3 percent), and skin or soft tissue (5.2 percent)

They reviewed global literature on typical antibiotic courses and found that the most common duration was 14 days. “Before BALANCE, there had been no randomized trials of antibiotic duration,” Daneman said.

Patients were randomly assigned 1:1 to either 7 or 14 days of antibiotic course, with a primary endpoint of 90-day mortality. More than half of the patients were critically ill and admitted to the ICU.

By 90 days, 261 patients (14.5 percent) in the 7-day antibiotic arm and 286 patients (16.1 percent) in the 14-day antibiotic arm had died (difference, −1.6 percentage points), demonstrating the noninferiority of the shorter treatment duration.

“Interestingly, receiving 7-day treatment up front led to less total antibiotic use during follow-up and shorter lengths of hospital stay,” Daneman reported.  

Seven-day treatment was as effective as 14 in other outcomes, including ICU mortality, hospital mortality, BSI relapse, and other markers.

A per-protocol analysis also showed noninferiority (difference, −2 percentage points). The findings were consistent across secondary clinical outcomes and prespecified subgroups defined according to patient, pathogen, and syndrome characteristics.

BSI strategy going forward

“We can say that 7 days use of antibiotics is noninferior to 14 in the treatment of BSI,” Daneman said, adding that the 7-day course should be the treatment strategy for BSIs going forward.

Dr Yohei Doi, professor of medicine at the University of Pittsburgh in Pittsburgh, Pennsylvania, US, who was not part of the study, said the results “may change clinical practice.”

“Currently, there’s no consensus on how long we should treat,” he said. “We were told 2 weeks of antibiotics is standard for bacteraemia. However, it has become shorter over time, with retrospective data suggesting that shorter treatment duration is as safe and effective as longer. We only get definitive answers when patients are randomly assigned as in BALANCE.”

What is not known

Current guidelines do not specify the duration of antibiotic use for bacteraemia because “very often, bacteraemia is only a secondary condition, for example, a urinary tract infection that spilt over into the bloodstream,” Daneman explained.

The “extremely tight” noninferiority margin of only 4 percent added confidence to the results. “For comparison, a noninferiority margin for a new drug seeking US FDA approval “typically could be between 7.5 percent and 15 percent,” he added.

Daneman shared that the team has already launched BALANCE +, a platform trial for patients with gram-negative BSIs, to inform clinicians of the best treatment approaches moving forward.