The POET trial: oral antibiotics in stable endocarditis patients noninferior to intravenous treatment

1. Patients with left sided infective endocarditis who switched to oral antibiotics once stable had similar composite adverse event outcomes compared to patients treated with 6 weeks of intravenous antibiotics.

2. Patients in the oral treatment group had hospital stays significantly shorter than those in the intravenous treatment

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Left sided infective endocarditis generally requires 6 weeks of closely monitored intravenous antibiotic treatment. Due to the complexity of treatment many patients require extended hospital stays to learn how their treatment should be safely administered. If oral antibiotic therapy was a safe and feasible treatment option, significant treatment adherence issues and costs associated with extended hospital stays could be avoided. The Partial Oral Treatment of Endocarditis (POET) trial sought to evaluate how patients with stable left sided endocarditis responded to intravenous versus oral antibiotic therapy. The primary outcome, a composite of adverse events associated with infective endocarditis, showed oral treatment was noninferior to intravenous treatment at 6 months after treatment randomization. Additionally, hospital stays for patients in the oral treatment group were significantly shorter than in the intravenous group.

This pragmatic randomized trial indicates a much more patient friendly oral antibiotic treatment regimen is a viable alternative to the traditional intravenous treatment infective endocarditis patients historically received. The study’s strengths include clinician guided choice of antibiotics and extensive subgroup analysis, while its limitations include exclusion of certain infectious organisms and limited generalizability of results as few patients evaluated for trial inclusion ultimately were enrolled in the trial.

Click to read the study in NEJM

Relevant Reading: Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review

In-Depth [randomized controlled trial]: This noninferiority, Danish, randomized controlled trial enrolled patients between 2011 and 2017. Eligible patients had infectious left sided endocarditis on native or prosthetic valves, had no indications for cardiac surgery, were in a stable clinical condition receiving intravenous antibiotics, and had positive blood culture for streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. If patients had at least 10 days of antibiotic treatment scheduled, they were eligible for randomization. Patients were randomized to oral (n=201) or intravenous (n=199) treatment groups. Patients in the oral group were eligible to receive treatment in in outpatient clinics, while intravenous group patients remained in the hospital. Antibiotics were chosen by the treating physicians. The primary outcome was a composite outcome of mortality, cardiac surgery, clinically relevant embolic events, or relapse of bacteremia within 6 months of trial randomization. Composite outcome events occurred in 12.1% and 9.0% of the intravenously and orally treated patients, respectively (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.37 to 1.36) indicating noninferiority of oral treatment. Incidence of embolic events, cardiac surgery, and bacteremia relapse were similar between the two groups, while incidence of death was greater in the intravenous group. For all subgroups assessed there was no discernable difference outcomes based on treatment received. Pharmacokinetics of orally administered antibiotics were measured, and no oral treatment regimens were changed based on plasma levels.

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