A response-tailored antibiotic strategy reduced treatment duration by approximately one-third compared with standard therapy without compromising safety in patients with left-sided infective endocarditis, according to the POET-II trial presented in a Hot Line session at the European Society of Cardiology Congress 2026 and published simultaneously in the New England Journal of Medicine1.
Current guidelines call for up to 6 weeks of high-dose antibiotics for left-sided infective endocarditis, a regimen based largely on historical data from the 1950s. The original POET trial established that clinically stable patients meeting defined criteria could safely transition from intravenous to oral antibiotics; POET-II investigators extended this work by testing whether treatment duration itself, not just route of administration, could be individualized based on early treatment response.
“Current recommendations of up to six weeks are based mostly on historical observations from the 1950s when lower doses of antibiotic monotherapy were used,” said Henning Bundgaard, MD, DMSc, principal investigator, Rigshospitalet-Copenhagen University Hospital. “We hypothesised that tailoring antibiotic therapy in those who have an initial positive response could safely reduce the duration of antibiotics.”1
POET-II trial design and primary endpoint results
POET-II was an investigator-initiated, open-label trial conducted at 13 centers in Denmark, Sweden, and the US. Clinically stable patients with left-sided endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococci were randomized to tailored therapy, with a minimum treatment duration of 2 to 4 weeks and discontinuation once predefined POET stabilization criteria were met, or to standard therapy following established guidelines. A total of 508 patients were randomized (255 to tailored therapy, 253 to standard therapy), with a mean age of 70 years and 75% men1. The tailored strategy reduced median total antibiotic duration to 26 days versus 41 days with standard therapy, a difference of 15 days (P < .001).
The primary endpoint, median days alive without antibiotic treatment within 6 months after randomization, favored the tailored-therapy group at 183 days versus 169 days in the standard-therapy group, a difference of 13 days (95% CI, 12-13; P < .001)1. Investigators noted this endpoint captures both survival and time free from ongoing antibiotic exposure, reflecting the clinical burden reduction sought by the tailored approach.
Safety outcomes and relapse rates with shortened therapy
The composite safety endpoint of all-cause mortality, unplanned heart valve surgery, or symptomatic embolic events within 6 months occurred in 8.2% of patients (21 of 255) in the tailored-therapy group versus 10.7% (27 of 253) in the standard-therapy group, meeting prespecified noninferiority criteria (difference, -2.4%; 95% CI, -7.7% to 2.7%)1. Noninferiority was preserved even when the higher relapse rate in the tailored group was factored into the composite analysis.
Primary relapse of infection, the principal safety concern with shortened antibiotic courses, occurred more frequently with tailored therapy than standard therapy (5.1% vs 1.6%; P = .04), though investigators reported these relapses were generally low in absolute number and easily managed with reinitiation of antibiotics1. Bundgaard characterized the findings as practice-changing, noting shorter courses may reduce antibiotic-related complications, microbial resistance, and treatment burden for patients.
“The results from our landmark trial have the potential to change clinical practice,” said Bundgaard. “We estimate that around half of the patients that we see in our clinics with left-sided infective endocarditis could be eligible for tailored reduced-duration antibiotic therapy.”1
Investigators positioned POET-II alongside the original POET trial, which showed oral step-down therapy was associated with a 39% reduction in 5-year mortality, as part of a broader effort to define the point of clinical stabilization at which less intensive antibiotic therapy becomes both safe and superior to prolonged standard regimens.2
References
European Society of Cardiology. Reducing antibiotic courses by two weeks could be possible in patients with infective endocarditis. Published August 28, 2026. Accessed August 29, 2026.
Iversen K, Ihlemann N, Gill SU, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Engl J Med. 2019;380:415-424. doi:10.1056/NEJMoa1808312
