A response-tailored strategy decreases antibiotic duration by 2 weeks compared with standard therapy in patients with left-sided infective endocarditis, without compromising their safety. This is the primary result of the POET-II study presented at ESC Congress 2026.
Furthermore, the response-tailored strategy has met the criteria for noninferiority as regards safety but is associated with an increased incidence of relapse of bacteraemia or infective endocarditis.
“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,” lead investigator Dr Henning Bundgaard, Department of Cardiology, Copenhagen University Hospital–Hjertecentret and Rigshospitalet, Copenhagen, Denmark, said in a press statement.
Of the 508 patients who met the eligibility criteria, 255 were assigned to response-tailored therapy and 253 to standard-duration therapy. [N Engl J Med 2026;doi:10.1056/NEJMoa2607887]
Treatment duration decreased by about one-third with the tailored strategy vs standard therapy, and the median total duration of antibiotic therapy was 26 and 41 days, respectively, representing a significant difference of 15 days (p<0.001).
The tailored therapy also resulted in a 2-week longer median time alive without antibiotic treatment than the standard therapy (183 vs 169 days; Hodges‒Lehmann estimated difference, 13 days, 95 percent confidence interval [CI], 12‒13; p<0.001 for superiority).
Safety profile
With respect to safety, 21 patients (8.2 percent) in the tailored strategy group and 27 (10.7 percent) in the standard therapy group died from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months after randomization (absolute between-group difference, ‒2.4 percentage points, 95 percent CI, ‒7.7 to 2.7; p<0.001 for noninferiority).
Additionally, relapse occurred more frequently with tailored therapy than with standard treatment (5.1 percent vs 1.6 percent; p=0.04).
The 5.1-percent relapse incidence with the primary pathogen that was observed with the tailored strategy was within the range of relapse incidence (2 percent to 9 percent) seen in previous studies and in the European Society of Cardiology guidelines. [Eur Heart J 2023;44:3948-4042; Clin Infect Dis 2005;41:406-409; Clin Microbiol Infect 2012;18:E522-E530; Clin Res Cardiol 2020;109:1342-1351]
“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.”
Trial details
Adults in stable condition with infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococcus species were included in this international, open-label, randomized trial. Participants received either response-tailored or standard-duration antibiotic therapy. Prior to the trial, patients received at least the prespecified 2‒4 weeks of therapy and met criteria for clinical stabilization.
After randomization, participants in the tailored strategy group discontinued antibiotics, while those in the standard therapy group continued treatment (total duration 4‒6 weeks).
The primary efficacy endpoint was days alive without antibiotics treatment for infective endocarditis or bacteraemia within 6 months after randomization, while the primary safety endpoint was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events. Relapse of bacteraemia or infective endocarditis served as a key secondary endpoint.
“The rationale for this trial builds on evidence from other types of bacterial infections, in which shorter antibiotic regimens have been found to be more effective and safe than the standard duration of treatment,” wrote Bundgaard and colleagues. [Clin Infect Dis 2009;48:713-721; Pharmacotherapy 2018;38:674-687; Lancet 2015;385:875-882]
A shorter antibiotic course may reduce the risk of adverse drug effects, complications, antimicrobial resistance, and costs. This strategy may also improve quality of life by reducing the physical and psychological toll associated with prolonged antibiotic treatment and hospitalization. [Int J Cardiol 2017;235:133-140; Med Care 2010;48:1026-1035; Aging Clin Exp Res 2009;21:453-457]
“Current recommendations of up to 6 weeks are based mostly on historical observations from the 1950s when lower doses of antibiotic monotherapy were used,” Bundgaard said. “We hypothesized that tailoring antibiotic therapy in those who have an initial positive response could safely reduce the duration of antibiotics.”