Frederick A. Masoudi, MD, MSPH

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.