A response-tailored antibiotic strategy reduced the duration of treatment by approximately one-third for patients with left-sided infective endocarditis without compromising safety, according to results from the POET-II trial. The findings were presented during a Hot Line session at the ESC Congress 2026 in Munich and published in the New England Journal of Medicine.
Tailored Antibiotic Strategy Reduces Treatment Duration for Heart Infection
Infective endocarditis is a life-threatening condition where the inner lining of the heart becomes infected, often alongside a bacterial infection in the bloodstream. If left untreated, the disease is fatal. Standard management typically involves high-dose antibiotics for up to six weeks, a recommendation based largely on historical observations from the 1950s when lower doses of monotherapy were utilized.
The POET-II trial, an investigator-initiated, open-label study conducted across 13 centers in the U.S., Sweden, and Denmark, sought to optimize this therapy by individualizing the duration of antibiotics for those showing a positive initial response.
Study Design and Patient Outcomes
The trial randomized 508 patients with left-sided endocarditis caused by streptococci, Enterococcus faecalis, or Staphylococcus aureus. The participants had a mean age of 70 years, and 75% were men. All patients first underwent a minimum of two to four weeks of antibiotic treatment to achieve clinical stability.
Patients were then assigned to one of two groups:
- Tailored Therapy: Antibiotics were discontinued once the predefined minimum treatment duration and POET stabilization criteria were met.
- Standard Therapy: Patients continued the typical regimen for a total duration of four to six weeks.
The tailored approach significantly shortened the treatment period. The median total duration of antibiotic therapy was 26 days for the tailored-therapy group compared to 41 days for the standard-therapy group, a difference of 15 days.
Efficacy and Safety Metrics
Researchers measured the primary efficacy endpoint as the median time alive and without antibiotic therapy for bacteremia or infective endocarditis within six months. The response-tailored group performed better, with a median of 183 days compared to 169 days in the standard duration group.
Regarding safety, the response-tailored therapy was found to be noninferior to standard therapy. The primary safety endpoint—which tracked symptomatic embolic events, unplanned cardiac surgery, or all-cause death at six months—was 8.2% for the tailored group and 10.7% for the standard group.
However, the trial noted a higher relapse rate in the tailored-therapy group at 5.1%, compared to 1.6% in the standard group. Despite this, the primary safety endpoint remained noninferior when the relapse rate was accounted for.
Clinical Implications and Context
Professor Henning Bundgaard, the trial’s Principal Investigator from Rigshospitalet – Copenhagen University Hospital, stated during a press conference that more than 50% of patients presenting with endocarditis may be candidates for this tailored treatment.
This study builds on the previous POET I trial, which established that patients with left-sided infective endocarditis could safely switch from intravenous to oral antibiotics if they met specific imaging, biochemical, and clinical criteria. Bundgaard noted that the stepped-down treatment in POET I was associated with a 39% reduction in mortality after five years.
The need for improved treatment strategies is underscored by the severity of infective endocarditis. Under modern treatment, mortality rates of 20–25% are reported if septic shock develops, and one-year mortality can reach 40%. Challenges in therapy are further compounded in elderly populations due to comorbidities, reduced organ functions, and increased susceptibility to antibiotic toxicity.
