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Study Summary

The randomized, multicenter Patient Oral versus Intravenous Antibiotic Treatment of Endocarditis (POET) trial of 400 stabilized adult patients with left-sided infective endocarditis, demonstrated that a strategy of intravenous (IV) antibiotics followed by oral antibiotics was noninferior to standard therapy with IV antibiotics for the 6-month primary composite outcome of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia (between-group difference 3.1%, -3.4 to 9.6%, P = 0.40) (see accompanying Hurst’s Central Illustration). The incidence of each component of the composite outcome was similar. Only patients with endocarditis due to streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci were included in this study and randomization occurred only after completing a period of IV antibiotics with 36% of the study population having already undergone cardiac surgery. There was no significant difference in rates of adverse events between those receiving IV antibiotics and those receiving oral antibiotics (6% vs. 5%, P = 0.66). No patients in the IV treatment group crossed over to the oral treatment group, whereas four patients in the oral treatment group crossed over to the IV group.


Study Strengths: POET is the first randomized trial to demonstrate the efficacy, safety, and feasibility of an abbreviated inpatient treatment plan in a select group of patients with stabilized left-heart endocarditis (i.e. patients who had already been treated with at least 10 days of intravenous antibiotics or those who had already underwent valvular surgery). The study population is clinically relevant as patients with high-risk features such as prosthetic valves, cardiac devices, significant valvular regurgitation, large vegetation size, and surgical cases were included. Both groups were well-matched with regard to baseline patient characteristics and there was limited crossover between groups.

Study Limitations: Outcomes from the POET trial can only be applied narrowly to the wider endocarditis population as only 20% of the screened population were eligible for randomization. Furthermore, there were limited cases involving IV drug users and no instances of methicillin-resistant S. aureus or other antibiotic-resistant species. In this trial, there was no patient attrition in follow-up, a feature unlikely to be replicated in non-clinical trial, real-world settings. Data on treatment compliance in the oral therapy group is not provided.

Next Steps/Clinical Perspective: The POET trial challenges the traditional notion that endocarditis mandates prolonged therapy with intravenous antibiotics, often in the hospital setting. Given the dangers of incompletely treated endocarditis, one must ensure that patient selection matches study criteria and that patients demonstrate compliance with specific oral antibiotic regimens examined and to the follow-up regimens followed in this study. In addition, real-world adoption of the POET trial would need to incorporate a transesophageal echocardiogram prior to discharge to ensure sufficient response to IV antibiotics. Further investigation is needed to determine if expedited hospitalization can be applied to a broader patient population with endocarditis, including those with right-sided endocarditis, endocarditis caused by less common bacterial organisms, and endocarditis refractory to initial IV antibiotic therapy.

Trial Reference

Iversen  K, Ihlemann  N, Gill  S, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N. Engl. J. Med. doi: 10.1056/NEJMoa1808312

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