Patients with infective endocarditis who were clinically stable after 2 to 4 weeks of initial antibiotic treatment lived longer with shorter, response-tailored periods of continued antibiotics than with the standard continuation regimens of up to 6 weeks, in an international randomized trial conducted to ascertain optimal antibiotic duration.1
"Current recommendations regarding the duration of antibiotic therapy are largely based on expert opinion and historical observations rather than randomized trials," indicate lead author Henning Bundgaard, MD, DMSc, Department of Cardiology, Copenhagen University Hospital and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, and POET II trial colleagues.
"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," the investigators explained.
The criteria for tailoring the antibiotic treatment to patient response were adapted from the Partial Oral Treatment of Endocarditis (POET) trial, which had established a shortened period of intravenous antibiotic before shifting to oral step-down treatment.2 Bundgaard and colleagues posited that response-tailored treatment based on the POET criteria could also reduce total duration of intravenous and oral antibiotic treatment by 2 to 3 weeks without compromising safety.
The investigators identified 634 adult patients at 13 sites in Denmark with left side heart infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococcus species. A total of 508 patients deemed clinically stable after initial antibiotic regimens were randomized to the two continued treatment conditions, with 255 receiving a shortened regimen following the tailored strategy and 253 the standard duration.
The primary efficacy outcome was number of days alive without antibiotic treatment or bacteremia within 6 months of randomization, statistically tested for superiority. A secondary endpoint was relapse of bacteremia or infective endocarditis. The primary safety outcome, tested for noninferiority, was a composite measure comprising death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months of randomization.
Bundgaard and colleagues reported that patients receiving the shortened, tailored antibiotic regimens lived 13 days longer than those on the longer standard regimens (indicating superiority at 183 days [interquartile range, 181 to 183] vs 169 days [166 to 171]. The shorter regimens were found non-inferior to longer duration in the safety end-point events (occurring in 21 patients with tailored therapy and in 27 patients receiving the longer duration). Relapse was more common with the shortened regimens, however, occurring in 13 patients (5.1%) with tailored treatment and in 4 (1.6%) with standard treatment duration.
What You Need to Know
In patients with stable infective endocarditis, response-tailored antibiotic regimens (2–3 weeks shorter than standard) led to significantly more days alive without antibiotics or bacteremia over 6 months compared to standard-duration treatment.
The shortened regimens were non-inferior to standard duration on the composite safety endpoint (death, unplanned cardiac surgery, or embolic events), even though relapse of infection was more frequent (5.1% vs. 1.6%).
Most relapses in the tailored-treatment group were uncomplicated and resolved by restarting antibiotics, suggesting the modest increase in relapse risk may be an acceptable tradeoff for reduced antibiotic exposure, cost, and side effects.
The investigators acknowledge that relapse of infection is a primary concern when considering shortening durations of antibiotic treatment, but report that most were uncomplicated and managed by reinitiating the antibiotic.While the relapses were associated with safety end point events, they also note that there was no overall difference between groups in the primary safety end point.
"Considering the potential benefits of a reduction in antibiotic exposure, an increase in the risk of relapse could be deemed acceptable if it is not associated with major clinical complications," Bundgaard and colleagues suggest.
Those benefits, they recount, include "fewer side effects, fewer healthcare-associated infections, a lower risk of antimicrobial resistance, decreased costs, and improved patient recovery and mental health."
References
1. Bundgaard H, Pries-Heje M, Hjulmand J, et al. Response-tailored or standard-duration antibiotic treatment for infective endocarditis. N Engl J Med. 2026, online August 28. doi:10.1056/NEJMoa2607887.
2. Iverson K, Ihlemann N, Gill SU, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Engl J Med. 2019; 380:415-424.
