A seven-day course of antibiotics may be associated with a higher risk of death among patients with Pseudomonas aeruginosa bacteremia compared with a 14-day regimen, according to a Bayesian analysis published in Clinical Infectious Diseases. The findings suggest that evidence supporting shorter antibiotic courses for gram-negative bloodstream infections may not apply equally to all pathogens.
Previous randomized clinical trials have demonstrated that seven days of antibiotic treatment is generally noninferior to 14 days for uncomplicated gram-negative bacteremia. However, uncertainty remains about the optimal treatment duration for P. aeruginosa, a pathogen that can cause severe bloodstream infections.
Researchers led by Arthur M. Albuquerque, MD, of the Federal University of Rio de Janeiro in Brazil, conducted a post hoc Bayesian analysis to investigate whether treatment duration was associated with different effects on the risk of death among patients with P. aeruginosa bacteremia and those with bloodstream infections caused by other gram-negative bacteria.
Examining treatment duration
The researchers analyzed data from five randomized clinical trials involving 4,032 patients, including 500 with P. aeruginosa bacteremia and 3,532 with other gram-negative bloodstream infections.
The analysis incorporated data from the BALANCE trial, the largest randomized study comparing seven- and 14-day antibiotic regimens, along with preliminary findings on deaths from SHORTEN-2, a trial specifically investigating treatment duration for P. aeruginosa bacteremia. Data from SHORTEN-2 were presented at the 2026 meeting of the Spanish Society of Infectious Diseases and Clinical Microbiology.
Using Bayesian statistical methods, the researchers estimated the probability that shorter antibiotic treatment increased or decreased the risk of death from any cause. Follow-up extended to 90 days in four trials and 30 days in SHORTEN-2.
Among patients with P. aeruginosa bacteremia, seven-day treatment was associated with an estimated risk ratio for death of 1.28 compared with 14-day treatment. The analysis indicated an 86% posterior probability that the shorter regimen increased the risk of death.
By contrast, among patients with other gram-negative bloodstream infections, seven-day treatment was associated with a risk ratio of 0.83, corresponding to a 98% posterior probability of a lower risk of death.
When comparing treatment effects between pathogen groups within trials, the researchers calculated a ratio of risk ratios of 1.42, with a 94% posterior probability that seven-day treatment was less favorable for P. aeruginosa bacteremia than for other gram-negative bloodstream infections.
Implications for clinical practice
The findings raise questions about applying standardized shorter antibiotic regimens across different causes of gram-negative bacteremia.
However, the study authors emphasized that the results remain exploratory. The direct subgroup comparison relied on just two trials, with BALANCE contributing 80% of patients with P. aeruginosa bacteremia in that analysis.
Additionally, the posterior probability of an increased risk of death in the P. aeruginosa subgroup ranged from 66% to 86%, depending on the statistical assumptions used, highlighting uncertainty about the estimated treatment effect.
The researchers also acknowledged that differences in patient characteristics, infection source control and other clinical factors could contribute to the observed outcomes.
Although shorter antibiotic courses remain supported for most uncomplicated gram-negative bloodstream infections, the authors suggested that clinicians should exercise caution when extrapolating these findings to P. aeruginosa bacteremia.
They concluded that although the overall evidence supports shorter antibiotic courses as the default approach for patients with bacteremia, additional randomized trials with sufficient statistical power to assess deaths are needed to determine whether seven-day treatment is appropriate for patients with P. aeruginosa bacteremia.
Study author Todd C. Lee, MD, reported Canadian Institutes of Health Research operating grant support and Fonds de recherche du Québec — Santé research salary support outside the submitted work. Dr. Lee also serves as an investigator for the BALANCE trial. All other authors declared no potential conflicts of interest. The remaining BALANCE investigators were informed of the manuscript but did not contribute to the reanalysis or its authorship.