Meeting NewsPerspective

POET: Switch to oral antibiotics confers better outcomes in left-sided endocarditis

Henning Bundgaard
Henning Bungaard

NEW ORLEANS — In long-term follow-up of patients with left-sided endocarditis, those who were switched from IV antibiotics to oral antibiotics after stabilization had better rates of survival and other outcomes, according to new data from the POET trial.

As Cardiology Today previously reported, among patients in stabilized condition with left-sided infective endocarditis caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus or coagulase-negative staphylococci who were on IV antibiotics for at least 10 days, those who were randomly assigned to switch to oral antibiotics had similar 6-month outcomes to those who were assigned to stay on IV antibiotics, and the group that was switched had a shorter hospital stay (3 days vs. 19 days after randomization).

Oral treatment included two antibiotics in all cases, chosen according to careful susceptibility testing.

For the present analysis, presented at the American College of Cardiology Scientific Session by Henning Bundgaard, MD, DMSc, from the department of cardiology, the Heart Center, Rigshospitalet, Copenhagen University Hospital, Denmark, and published as a research letter in The New England Journal of Medicine, the researchers analyzed the 400-patient cohort after a median follow-up of 3.5 years.

The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteremia with the primary pathogen. No patients were lost to follow-up.

During the study period, the oral group had reduced risk for the primary outcome compared with the IV group (26.4% vs. 38.2%; HR = 0.64; 95% CI, 0.45-0.91), according to the researchers.

In long-term follow-up of patients with left-sided endocarditis, those who were switched from IV antibiotics to oral antibiotics after stabilization had better rates of survival and other outcomes, according to new data from the POET trial.
Source: Adobe Stock

Mortality was also lower in the oral group (16.4% vs. 27.1%; HR = 0.57; 95% CI, 0.37-0.87) and differences in the other three components of the primary outcome were not significant between the groups, Bundgaard said.

“The favorable outcome in the oral group was not related to the administration of antibiotics,” Bundgaard said during a discussion after his presentation. “It’s fair to say that short term and long term, there were no differences in [patients who did not respond to antibiotics] between the two groups. So, I don’t think the results related to the different ways of administration. The major difference between the two groups was that the intravenously treated patients stayed in the hospital for more than 2 weeks longer than the orally treated patients. We all know that staying in the hospital may cause physical as well as mental losses. These patients’ capacities are reduced, and they are quite often elderly and sick with comorbidities. So, maybe they don’t ever recover from their losses after their prolonged hospital stays. This will increase vulnerability and make the patients at higher risk of a negative outcome when struck by another disease, such as heart failure, infection or cancer.”

The mean age of the patients in both groups was 67 years. The oral group consisted of 21% women, whereas the IV group consisted of 25% women. – by Erik Swain

References:

Bundgaard H, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.

Bundgaard H, et al. N Engl J Med. 2019;doi:10.1056/NEJMc1902096.

Disclosure: Bundgaard reports no relevant financial disclosures.

 

Henning Bundgaard
Henning Bungaard

NEW ORLEANS — In long-term follow-up of patients with left-sided endocarditis, those who were switched from IV antibiotics to oral antibiotics after stabilization had better rates of survival and other outcomes, according to new data from the POET trial.

As Cardiology Today previously reported, among patients in stabilized condition with left-sided infective endocarditis caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus or coagulase-negative staphylococci who were on IV antibiotics for at least 10 days, those who were randomly assigned to switch to oral antibiotics had similar 6-month outcomes to those who were assigned to stay on IV antibiotics, and the group that was switched had a shorter hospital stay (3 days vs. 19 days after randomization).

Oral treatment included two antibiotics in all cases, chosen according to careful susceptibility testing.

For the present analysis, presented at the American College of Cardiology Scientific Session by Henning Bundgaard, MD, DMSc, from the department of cardiology, the Heart Center, Rigshospitalet, Copenhagen University Hospital, Denmark, and published as a research letter in The New England Journal of Medicine, the researchers analyzed the 400-patient cohort after a median follow-up of 3.5 years.

The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteremia with the primary pathogen. No patients were lost to follow-up.

During the study period, the oral group had reduced risk for the primary outcome compared with the IV group (26.4% vs. 38.2%; HR = 0.64; 95% CI, 0.45-0.91), according to the researchers.

In long-term follow-up of patients with left-sided endocarditis, those who were switched from IV antibiotics to oral antibiotics after stabilization had better rates of survival and other outcomes, according to new data from the POET trial.
Source: Adobe Stock

Mortality was also lower in the oral group (16.4% vs. 27.1%; HR = 0.57; 95% CI, 0.37-0.87) and differences in the other three components of the primary outcome were not significant between the groups, Bundgaard said.

“The favorable outcome in the oral group was not related to the administration of antibiotics,” Bundgaard said during a discussion after his presentation. “It’s fair to say that short term and long term, there were no differences in [patients who did not respond to antibiotics] between the two groups. So, I don’t think the results related to the different ways of administration. The major difference between the two groups was that the intravenously treated patients stayed in the hospital for more than 2 weeks longer than the orally treated patients. We all know that staying in the hospital may cause physical as well as mental losses. These patients’ capacities are reduced, and they are quite often elderly and sick with comorbidities. So, maybe they don’t ever recover from their losses after their prolonged hospital stays. This will increase vulnerability and make the patients at higher risk of a negative outcome when struck by another disease, such as heart failure, infection or cancer.”

The mean age of the patients in both groups was 67 years. The oral group consisted of 21% women, whereas the IV group consisted of 25% women. – by Erik Swain

References:

Bundgaard H, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.

Bundgaard H, et al. N Engl J Med. 2019;doi:10.1056/NEJMc1902096.

Disclosure: Bundgaard reports no relevant financial disclosures.

 

    Perspective
    Frederick A. Masoudi

    Frederick A. Masoudi

    This is an interesting study comparing the longstanding standard care for left-sided bacterial endocarditis, which is long-term IV antibiotics, with an oral regimen after an initial period of IV therapy. The original study assessed a composite of all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteremia at 6 months. The trial found that the oral antibiotic regimen followed by initial IV therapy was not inferior to the standard 6-week course of IV therapy. 

    These new data provide longer-term information on outcomes between the two groups, with a median follow-up of 3.5 years; some participants were followed as long as 7 years. In this longer-term analysis, outcomes were actually better in the group that received oral antibiotic therapy than in those who stayed on IV therapy. These additional data are important because the 6-month follow up from the primary results may not be adequate time to identify all the potential complications that might emerge with a different treatment regimen for endocarditis.

    The event curves for the primary endpoint do not begin to diverge until about 1 year. It’s possible this is due to a “hangover effect” from the adverse consequences of a longer hospital stay for the initial treatment. However, it is most prudent to interpret the trial based on its principal findings of noninferiority at 6 months. Nevertheless, I interpret these secondary findings as reassurance that this relatively revolutionary treatment strategy for left-sided endocarditis can be safe, at least in some circumstances.

    For individuals who meet the criteria of this trial — left-sided endocarditis with Streptococcus, Enterococcus, or Staphylococcus without evidence of significant complications such as a valve abscess, who have responded well to initial treatment with IV antibiotics after a course of about 10 days, who are now afebrile and for whom evidence of inflammation has waned (lower levels of C-reactive protein and white blood cell counts), it would be reasonable to consider a switch to a two-drug oral regimen. I would only consider this for individuals who I believe will be adherent to outpatient oral therapy and can get close clinical follow-up. Even assuming that the IV followed by oral antibiotic therapy is not inferior to the standard approach, there may be additional benefits. It will shorten time in the hospital, which could reduce cost and the potential adverse consequences of hospitalization.

    For these reasons, this approach may catch on for the treatment of selected individuals with left-sided endocarditis. There are certain individuals in whom a switch to oral antibiotics would not necessarily be the best approach, such as those who do not fit the POET enrollment criteria or who are unlikely to be able to adhere to an outpatient oral regimen.

    I would expect there to be some inertia in the clinical community in adopting this strategy. The idea of providing IV antibiotics for 6 weeks for left-sided endocarditis is strongly ingrained in clinical practice. Thus, while the results of this trial are encouraging, and should stimulate the development of protocols for switching to oral therapy, some experience will be necessary, with success building upon success, before this strategy is widely implemented.

    Surveillance in the real-world setting, looking at treatment patterns for endocarditis, including adoption and real-world outcomes of this practice, would be helpful. Mechanisms to assess uptake of the practice, to ensure those being selected for the oral therapy protocol are appropriate for the treatment and to assess outcomes in the real world with respect to medication adherence and history of relapse, are critical. Performing such surveillance on a large scale is difficult outside of a registry program; currently, there are no U.S. national endocarditis registries.

    The study also shows the value of randomized trials that challenge deeply held convictions about optimal treatment strategies. The comparison needs to be acceptable for an institutional review board to accept the assumption of equipoise between the new therapy and standard care, as was the case in this trial. The investigators enrolled a population who would succeed on an oral regimen. This trial pushed the envelope in identifying a care strategy that is potentially better and cost-saving when appropriately implemented.

    • Frederick A. Masoudi, MD, MSPH
    • Professor of Medicine
      Division of Cardiology
      Department of Medicine
      University of Colorado School of Medicine
      Anschutz Medical Campus
      Chief Science Advisor
      American College of Cardiology’s National Cardiovascular Data Registry

    Disclosures: Masoudi reports no relevant financial disclosures.

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