Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis.

August 28, 2026| Source: The New England journal of medicine

In patients with infective endocarditis on the left side of the heart, the current recommendation of up to 6 weeks of antibiotic therapy is based largely on expert consensus opinion. Whether a clinical response-tailored antibiotic management strategy can shorten treatment duration without compromising safety is unclear. In this international, open-label, randomized trial, we assigned adults in stable condition with infective endocarditis caused by Staphylococcus aureus , Enterococcus faecalis , or streptococcus species to receive either response-tailored or standard-duration antibiotic therapy. Before randomization, all the patients received at least the prespecified 2 to 4 weeks of therapy and met criteria for clinical stabilization. After randomization, patients in the tailored-therapy group discontinued antibiotics and those in the standard-therapy group continued standard treatment (total duration, 4 to 6 weeks). The primary efficacy end point was days alive without antibiotic treatment for infective endocarditis or bacteremia within 6 months after randomization (tested for superiority). The primary safety end point was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months after randomization (tested for noninferiority; margin, 7.5 percentage points). Relapse of bacteremia or infective endocarditis was a key secondary end point. A total of 508 patients underwent randomization, with 255 assigned to response-tailored therapy and 253 to standard-duration therapy. The median time alive without antibiotic treatment was 183 days (interquartile range, 181 to 183) with tailored therapy and 169 days (interquartile range, 166 to 171) with standard therapy (Hodges-Lehmann estimated difference, 13 days; 95% confidence interval [CI], 12 to 13; P<0.001 for superiority). A primary safety end-point event occurred in 21 patients (8.2%) with tailored therapy and in 27 patients (10.7%) with standard therapy (absolute between-group difference, -2.4 percentage points; 95% CI, -7.7 to 2.7; P<0.001 for noninferiority), indicating noninferiority. Relapse occurred in 13 patients (5.1%) with tailored therapy and in 4 patients (1.6%) with standard therapy (P = 0.04). Among patients with infective endocarditis on the left side of the heart, the use of a response-tailored antibiotic strategy resulted in a longer time alive without antibiotic therapy than standard-duration therapy and met the criterion for noninferiority with respect to safety but was associated with a higher incidence of relapse of bacteremia or infective endocarditis. (Funded by Sygeforsikringen "danmark" and others; POET II ClinicalTrials.gov number, NCT03851575.).

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