麻豆传媒

MUNICH -- Switching to oral antibiotics once an endocarditis patient is stable appears safe and could allow them to head home from the hospital sooner, the randomized showed.

The group getting oral tablets after at least 10 days IV antibiotics had a 9.0% rate of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen by 6 months after completion of treatment.

That rate was noninferior to the 12.1% in the IV-only antibiotic group (HR 0.72, P=0.40), Henning Bundgaard, MD, of Rigshospitalet in Copenhagen, reported here at the European Society of Cardiology meeting and simultaneously online in the New England Journal of Medicine.

Notably, length of hospital stay after randomization was 19 days with IV-only antibiotics compared with 3 days in the oral switch group (P<0.001) although Bundgaard cautioned this was not a predefined outcome.

"We consider this new treatment may halve the hospital stays for patients with a heart valve infection," Bundgaard said at a press conference. "In most patients with even serious infections of heart valves, treatment with antibiotics as tablets is as good as presently-used injections of antibiotics."

Guidelines have called for treating left-sided infectious endocarditis with IV antibiotics for up to 6 weeks, but based largely on consensus around observational findings. With 400 patients, POET is by far the largest clinical trial to be done in endocarditis.

This group of stable patients may represent 40% of endocarditis cases, commented Kurt Huber, MD, of the Medical University of Vienna.

"For the patients this might be nice to stay at home, to sleep at home," he said. On the other hand, he noted, patients in the trial had to return to the hospital two to three times per week to be checked for fever and other signs of trouble with antibacterial effectiveness, which could pose a problem for those who don't live nearby.

Even so, "hospital stay is expensive and puts patients at risk for further infection," noted study discussant Christopher Peter Gale, MBBS, PhD, of the University of Leeds, England.

It's plausible that the shorter stay accounted for the numerically lower adverse events, as patients who stay in the hospital longer could be at greater risk of events such as hospital-acquired infection, Huber noted.

However, Gale argued caution in routinely applying the trial protocol, especially given the strict inclusion and exclusion criteria (only 20% of patients evaluated were accepted for randomization) and careful, frequent monitoring of outpatient antibiotics. "They were very well patients," he said, noting clinical and biochemical stability confirmed before randomization.

The open-label trial included 400 adults in stable condition with endocarditis on the left side of the heart caused by Streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with IV antibiotics for a minimum of 7 to 10 days. They were at least a week out from any surgery and had no fever of 38°C or higher for more than 2 days.

All got transesophageal echocardiograms to rule out abscess or valve requiring surgery before randomization; guideline-adherent treatment by an endocarditis team; and two antibiotics in different classes. Patients with potential for reduced antibiotic absorption were excluded, including those with a BMI over 40. Outpatient monitoring incorporated both drug plasma levels and elimination half-life, with drug dosing tailored to the minimum inhibitory concentration.

Components of the primary endpoint were similar between treatment groups except for mortality, which was numerically but not significantly higher in the IV group (13 deaths versus 7 in the oral group). Findings were similar across subgroups, including native versus prosthetic valve.

As to safety, seven patients in the oral antibiotics group had a plasma concentration of one of the two administered antibiotics that dropped below the most effective level. But none of these patients had both drugs drop below the most effective level, and no primary endpoint events occurred among them. Antibiotic-related adverse event rates were similar between treatment groups.

Bundgaard noted that there is low antibiotic resistance in Scandinavian countries like Denmark, where the trial was done, which may limit generalizability to others with higher prevalence of resistance. He speculated that the findings would be applicable to the United States, despite some issues with resistance there.

An informal poll of the audience at the late-breaking clinical trial session showed a big shift, with 66% saying they would order IV therapy for the full duration before the presentation but only 19% saying so after it.

"Whether the results are maintained in the long term and healthcare costs are reduced is as yet unknown," Gale cautioned. "Should we elect to adopt POET to practice, I would recommend strict adherence to the patient selection and the monitoring criteria."

Comment