Patients hospitalized with a serious heart valve infection could finish antibiotics about two weeks earlier when treatment length is matched to how quickly they stabilize, according to results from the POET-II trial presented at the European Society of Cardiology Congress in Munich and published simultaneously in the New England Journal of Medicine.
The trial cut median total antibiotic duration from 41 days to 26, roughly a one-third reduction, and met its prespecified noninferiority criterion for the primary safety outcome. It also produced a finding that has to be reported alongside the headline: relapse of bacteremia or endocarditis occurred more often in the shortened group, 5.1 percent compared with 1.6 percent.
Infective endocarditis is an infection of the heart's inner lining, often accompanied by bacteria in the bloodstream. Without antibiotics, it can be fatal. Standard management involves high-dose antibiotics for up to six weeks, frequently requiring prolonged hospitalization or outpatient intravenous therapy at home.
The Stabilization Point as a Decision Tool
POET-II was an investigator-initiated, open-label trial conducted at 13 centers in Denmark, Sweden, and the United States. It enrolled 508 clinically stable patients with left-sided endocarditis caused by Staphylococcus aureus, Enterococcus faecalis or streptococci. Mean age was 70 years, and 75 percent were men.
Patients were randomized to response-tailored therapy, with a minimum of two to four weeks of antibiotics, or to standard-duration therapy. In the tailored group, antibiotics were stopped once patients had both completed the minimum duration and met predefined stabilization criteria drawn from the earlier POET trial, which had established that selected patients could switch safely from intravenous to oral antibiotics.
Henning Bundgaard, the principal investigator from Rigshospitalet at Copenhagen University Hospital, was blunt about why six weeks became the norm in the first place. "Current recommendations of up to six weeks are based mostly on historical observations from the 1950s when lower doses of antibiotic monotherapy were used," he said. He described the stabilization criteria as the key to the new approach, saying they "appear to identify a turning point beyond which antibiotic treatment can be safely de-escalated."
The primary endpoint, days alive without antibiotic treatment within six months of randomization, favored the tailored group at a median of 183 days versus 169 days. Bundgaard estimated that around half of patients seen with left-sided infective endocarditis could be eligible for a reduced-duration regimen, according to a trial summary published by the American College of Cardiology.
The Relapse Signal in Plain Terms
Thirteen relapses occurred in the tailored group compared with four in the standard group, a statistically significant difference. Investigators reported that most relapses were managed by restarting antibiotics.
The safety endpoint combined all-cause mortality, unplanned heart valve surgery, and symptomatic embolic events within six months. It occurred in 8.2 percent of the tailored group and 10.7 percent of the standard group, comfortably meeting the noninferiority threshold. Noninferiority is the right frame here. The trial was built to show that a shorter course does not make patients worse, not that it makes them better.
This is why the framing matters. The trial does not show that shorter antibiotic courses are better for everyone with endocarditis. It shows that in carefully selected, clinically stable patients with specific organisms who meet defined stabilization criteria, a shorter course did not compromise the primary safety outcome while producing more relapses that generally responded to renewed treatment.
The trial was open-label, meaning clinicians and patients knew the assigned strategy, which can influence how symptoms are reported and how quickly a relapse is identified. The results are also specific to left-sided infection caused by three organism groups, and say nothing about right-sided endocarditis, other pathogens, or unstable patients. One discussant at the congress noted that patients with Enterococcus faecalis infection may warrant particular caution, since they could be at greater relapse risk on a shortened course.
The Case for Getting Off Antibiotics Sooner
The reason clinicians pursue shorter courses is not convenience. Weeks of high-dose intravenous antibiotics carry their own costs, including line infections, kidney and liver effects, disruption of gut bacteria, and the risk of Clostridioides difficile infection.
Bundgaard pointed to quality of life, saying shorter courses may reduce the physical and psychological toll associated with prolonged treatment and hospitalization. For a 70-year-old spending six weeks tethered to an intravenous line, two weeks back is meaningful time at home.
There is also a population-level argument. Reducing total antibiotic exposure is a recognized goal in limiting the development of resistant organisms, and shorter durations have already proven safe and effective across several other infections.
Funding came from unrestricted grants from a set of Danish foundations and public research funds. Bundgaard reported lecture fees from Amgen, MSD, BMS, Sanofi and GE.
Patients Should Not Ask to Stop Early
The most important practical message is restraint. Nobody being treated for endocarditis should ask to shorten a course, and nobody should stop antibiotics early. Doing so in a patient who has not met stabilization criteria risks a relapse that can damage a valve, seed infection elsewhere or become life-threatening.
Practice has not changed. Current recommendations still call for treating left-sided infective endocarditis with antibiotics for up to six weeks, and any move toward response-tailored duration would require guideline review by professional societies and careful patient selection at the bedside.
Patients and families can reasonably ask which organism was identified, whether the infection is left-sided or right-sided, what criteria the team uses to judge stabilization, and what the plan is for monitoring after antibiotics end. Because relapse is a documented risk in the shortened approach, understanding what follow-up looks like is more useful than negotiating the calendar.
Anyone who has been treated for endocarditis and later develops recurring fever, night sweats, new fatigue, unexplained weight loss, or new shortness of breath should contact their care team promptly rather than waiting for a scheduled appointment. Those can be signs of a relapse that is treatable when caught early.
Key Questions Answered
What is infective endocarditis? An infection of the inner lining of the heart, often occurring alongside bacteria in the bloodstream. It can be fatal without antibiotics, and standard treatment involves high-dose antibiotics for up to six weeks.
What did the POET-II trial test? Whether antibiotic duration could be tailored to a patient's early treatment response rather than following a fixed schedule. It enrolled 508 clinically stable patients at 13 centers in Denmark, Sweden, and the United States.
How much shorter was treatment? Median total antibiotic duration was 26 days in the tailored group compared with 41 days in the standard group, about a one-third reduction.
Were there downsides? Yes. Relapse of bacteremia or endocarditis occurred in 5.1 percent of the tailored group compared with 1.6 percent of the standard group. Investigators reported that most relapses were managed by restarting antibiotics.
Does this change treatment today? No. Current recommendations still call for up to six weeks of antibiotics for left-sided infective endocarditis. Any change would require guideline review and careful patient selection.
What symptoms suggest a relapse? Recurring fever, night sweats, new fatigue, unexplained weight loss or new shortness of breath after treatment. Anyone with these should contact their care team promptly.
