TOPLINE

Among patients with infective endocarditis on the left side of the heart, a response-tailored antibiotic strategy shortened the duration of treatment by about 15 days compared with standard therapy, resulting in 13 more days alive without antibiotic treatment. However, the tailored approach was associated with a higher rate of relapse of bacteraemia or endocarditis.

METHODOLOGY

• Researchers conducted a randomised trial to evaluate whether a response‑tailored strategy could shorten the duration of antibiotics in patients with left-sided infective endocarditis without compromising safety.
• A total of 508 patients (mean age, 70 years; 75.4% men) completed a prespecified 2-4 weeks of therapy and met the criteria for clinical stabilisation before randomisation.
• These patients were then assigned in a 1:1 ratio to receive either response-tailored therapy, in which antibiotics were discontinued immediately, or standard-duration therapy, in which antibiotics continued for a total of 4-6 weeks.
• The primary efficacy endpoint was the number of days alive without antibiotic treatment for infective endocarditis or bacteraemia within 6 months.
• The primary safety endpoint was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months; relapse with the primary pathogen served as a key secondary endpoint.

TAKEAWAY

• Patients on tailored therapy spent a median of 183 days alive without antibiotic treatment compared with 169 days for those on standard therapy (between-group difference, 13 days; P < .001 for superiority).
• The total antibiotic duration was reduced: a median of 26 days with tailored therapy vs 41 days with standard therapy, corresponding to a 15-day absolute reduction and a 36.6% relative reduction.
• The tailored strategy met the trial's non-inferiority criterion for safety, with the composite endpoint occurring in 8.2% of patients on tailored therapy vs 10.7% of those on standard therapy (absolute between-group difference, -2.4 percentage points; P < .001 for non-inferiority).
• However, patients on tailored therapy relapsed more often than those on standard therapy (5.1% vs 1.6%; P = .04).

IN PRACTICE

"The shorter duration of antibiotic therapy, by 15 days, with response-tailored therapy corresponded to approximately one third of the duration of standard antibiotic treatment," the authors of the study wrote.

SOURCE

The study was led by Henning Bundgaard, MD, DMSc, Copenhagen University Hospital-Hjertecentret and Rigshospitalet, Copenhagen, Denmark. It was published online on August 28, 2026, in The New England Journal of Medicine.

LIMITATIONS

The trial enrolled only patients with left‑sided infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or Streptococcus species, so the findings may not have extended to infections caused by rarer pathogens. Most patients were enrolled in Denmark, and few had intravenous substance use disorder, which may have further limited the generalisability of the results to other populations and healthcare settings.

DISCLOSURES

The trial was supported by unrestricted grants from multiple sources, including Sygeforsikringen "danmark," Danmarks Frie Forskningsfond, Thora og Viggo Groves Mindelegat, Regionernes Medicinpulje, and Arvid Nilssons Fond. Several authors reported having various ties — including receiving research grants or lecture fees, holding stocks, or serving in data and safety monitoring board roles — with a wide range of pharmaceutical and device companies. One author disclosed being a deputy editor of The New England Journal of Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.