A response-tailored strategy reduced antibiotic duration by two weeks without compromising the safety of patients with left-sided infective endocarditis. This was the main finding from the POET-II trial presented in a Hot Line session today at ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.
In infective endocarditis, the heart's inner lining becomes infected, often in parallel with a bacterial infection in the bloodstream. Without antibiotics, infective endocarditis can be fatal.
Current management involves high-dose antibiotics for up to six weeks. It has been shown previously in the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis (POET) I trial that patients with left-sided infective endocarditis can be safely switched from intravenous antibiotics to oral antibiotics if they fulfil certain clinical, biochemical and imaging criteria, known as the POET criteria.
Seeking to further optimize antibiotic therapy, POET investigators turned their attention to individualizing the duration of antibiotics.
Current recommendations of up to six weeks are based mostly on historical observations from the 1950s when lower doses of antibiotic monotherapy were used. We hypothesized that tailoring antibiotic therapy in those who have an initial positive response could safely reduce the duration of antibiotics."
Professor Henning Bundgaard, Principal Investigator of the POET-II trial, Rigshospitalet - Copenhagen University Hospital, Denmark
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 duration of 2-4 weeks of antibiotic treatment, or to standard therapy. In the tailored-therapy group, antibiotics were discontinued once the predefined minimum treatment duration and POET stabilisation criteria were met. A total of 508 patients were randomized who had a mean age of 70 years; most (75%) were men.
The tailored strategy reduced treatment duration by approximately one-third compared with standard treatment. The median total duration of antibiotic therapy was 26 days in the tailored-therapy group and 41 days in the standard-therapy group, representing a significant difference of 15 days (p<0.001).
The primary endpoint - the median number of days alive without antibiotic treatment within six months after randomisation - was significantly longer in the tailored-therapy group than in the standard group (183 days vs. 169 days; p<0.001).
There was no compromise on safety with reduced treatment duration. The safety endpoint of all-cause mortality, unplanned heart valve surgery or symptomatic embolic events within six months occurred in 8.2% of patients in the tailored-therapy group vs. 10.7% on standard therapy, and met noninferiority criteria.
The main concern related to shorter duration of antibiotic therapy is relapse of infection. The researchers found that rates of primary relapse were low but were more frequent in the tailored- vs. the standard-therapy group (5.1% vs. 1.6%; p=0.04); however, most were easily managed with reinitiation of antibiotics.
"The results from our landmark trial have the potential to change clinical practice," concluded Professor 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." He highlighted the benefits of shorter courses of antibiotic therapy related to side effects, complications, microbial resistance and lower costs. "Shorter courses of antibiotics may also improve patients' quality of life by reducing the physical and psychological toll associated with prolonged antibiotic treatment and hospitalizations," he added as a final note.
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