Switch to Oral Antibiotics Safe in Left-Sided Endocarditis, Slashes LOS

Patrice Wendling

August 29, 2018

MUNICH — The largest randomized, controlled trial in infective endocarditis has shown that stabilized patients with left-sided endocarditis can be safely switched from intravenous to oral antibiotics — sparing them weeks of in-hospital treatment.

Partial oral antibiotic therapy in the POET trial was as good as intravenous (IV)-only therapy for the primary composite endpoint of all-cause death, unplanned cardiac surgery, embolic events, or relapse of bacteremia at 6 months.

The findings were consistent across subgroups, including type of bacteria, native vs prosthetic heart valves, and surgically vs conservatively treated patients.

"Based on these results, more than 50% of all patients with endocarditis may be candidates to partial oral antibiotic treatment," study author Henning Bundgaard, MD,  said in a hotline session at the European Society of Cardiology (ESC) Congress 2018. The findings were also published online August 28 in the New England Journal of Medicine.

He explained that guidelines recommend treatment of left-sided endocarditis with IV antibiotics for up to 6 weeks in the hospital, which is associated with high in-hospital complication and mortality rates, mainly in the early phase.

There is reasonable evidence that right-sided endocarditis can be treated with oral antibiotics following IV administration, but few trials have examined the effectiveness and safety of this strategy in left-sided endocarditis, where the stakes are generally higher.

To explore this, investigators screened 1954 patients referred to a cardiac center in Denmark between July 2011 and August 2017 for suspected endocarditis. After exclusions, 400 patients (77% men; mean age, 67 years) treated with IV antibiotics for left-sided endocarditis caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci were randomly assigned to continue IV treatment (n = 199) or switch to oral treatment (n = 201).

The median time from diagnosis to randomization was 17 days in both groups. About a third of patients had prosthetic valves.

The primary composite endpoint occurred in 12.1% of patients in the IV group and 9% of patients in the oral group (between-group difference, 3.1 percentage points; 95% confidence interval, –3.4 to 9.6 percentage points; P = .40), which met the trial's noninferiority margin, Bundgaard reported.

Rates were identical in the two groups for the individual components of unplanned cardiac surgery (6 each), embolic event (3 each), and reinfection (5 each). There were fewer deaths in the oral group than in the IV-only group (7 vs 13), although it is unclear why, he said.

After randomization, the oral group had to stay in hospital for a median of only 3 days vs 19 days in the IV group (P < .001), although this was not a prespecified outcome, Bundgaard said.

"We consider this new treatment may halve the hospital stays of patients with heart valve infection," he said during a press conference.

He observed that Denmark has low rates of antibiotic resistance compared to countries with more liberal antibiotic use, but added, "In the US this would certainly also be applicable, even though there are issues in the US with resistance."

Concerns were also raised about the generalizability of follow-up care in the oral group, which included two to three outpatient visits per week during ward rounds.

"That is how we did it but I think you will have to do in different ways in different hospital systems," he said.

American Heart Association Past-President Mariell Jessup, MD, Leducq Foundation, Boston, Massachusetts, commented to theheart.org | Medscape Cardiology that "In the United States, there are enough primary care, cardiology offices that have qualified nurse practitioners that could, in theory, see these patients. So I think you could work that out.

"The thought that crossed my mind was, How do you ensure that the patient is taking the pills? I think that has to do with patient selection. I certainly doubt that an IV drug abuser would be someone who would go home on pills. So I don't think these are unsurmountable problems."

Jessup called the POET trial a "very brave study and one that really needs to be done."

"To have a precedent in a study like this that shows that you could, in theory, choose some patients to go home on pills is terrific," she said. "It could save a lot of money and make patients less miserable."

Invited discussant Chris P. Gale, MD, University of Leeds, United Kingdom, praised the trial design and said a major advantage is that it included the leading pathogens of native and prosthetic valve endocarditis.

"Should the results of the POET trial be implemented into our routine clinical practice? I would argue that we should be cautious based on two principles: one is the generalizability of these results and two is the fact that there are some unknowns," he said.

Gale noted that the trial had very strict inclusion and exclusion criteria, there was frequent monitoring of drug plasma levels and half-life, and dosing was tailored to the minimum inhibitory concentration. Patients with any potential for reduced antibiotic absorption were excluded.

Also, all patients received two antibiotics intravenously for a minimum of 7 to 10 days, they were clinically and biochemically stable, and they underwent transesophageal echocardiography before randomization to rule out abscess or valve reinfection requiring surgery.

"So the 'O' in POET doesn't imply outpatient therapy," Gale quipped. "Indeed, outpatients were only selected if they had no heart failure, no emboli, no arrhythmia, no complicating comorbidities, and they were frequently and strictly monitored." 

Unknowns include covert infection rates, health-related quality of life, longer-term results, and healthcare costs savings.

"Should we elect to adopt POET into practice, then strict adherence to the patient selection and monitoring criteria is recommended," Gale concluded.

Commenting to theheart.org | Medscape Cardiology, Frederick Masoudi, MD, University of Colorado-Denver, said oral antibiotic treatment would be challenging in any healthcare system and that related nursing care would add to the cost of the strategy, although it will still be substantially lower than that for parenteral therapy.

"It will take a systematic approach to follow up to really successfully adopt something like this," but "I think this opens the door," he said "It's very provocative, challenging a long-held belief that oral regimens are just a no-no for left-sided endocarditis."

The audience appeared to be swayed by the POET results based on a survey that asked what they would do for a patient who had responded well to 2 weeks of IV antibiotics for methicillin-sensitive staphylococcal native mitral valve endocarditis. Before the presentation, 66% of attendees said they would continue IV therapy for another 2 to 4 weeks, but this dropped to just 19% after the presentation and Gale's critique — eliciting a "Wow" from the panel and a hearty round of applause from the Hotline Session audience.

The study was supported by unrestricted grants from the Danish Heart Foundation, Capital Regions Research Council, Hartmann's Foundation, and Svend Aage Andersens Foundation. Bundgaard reported having no relevant financial relationships.

European Society of Cardiology (ESC) Congress 2018.

N Engl J Med. Published online August 28, 2018. Full text

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.