Early Switch from Intravenous to Oral Antibiotic Therapy for Left-Sided Endocarditis POET trial (Partial Oral Treatment of Endocarditis)

Among patients who had left-sided infective endocarditis (IE) caused by common bacteria, a shift from intravenous (IV) to oral antibiotic treatment was noninferior to continued IV antibiotic treatment, according to the open-label, randomized POET trial (Partial Oral Treatment of Endocarditis; ClinicalTrials.gov: NCT01375257). Contemporary practice guidelines from the US and Europe recommend a 4- to 6-week course of IV antibiotics for patients with a left-sided IE. Data from the POET trial suggest that oral antibiotics may be safely and effectively administered during approximately half of the recommended treatment period, and potentially as outpatient treatment. The study results were presented at the European Society of Cardiology Congress 2018 and published in the New England Journal of Medicine.

The multicenter, nationwide Danish study enrolled 400 of 1954 screened patients who had Duke criteria-confirmed IE on the left side of the heart caused by Streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. After being stable on IV antibiotics for at least 10 days, patients were randomized in a 1:1 ratio to a shift to oral antibiotic treatment (201 patients) or continued IV antibiotic treatment (199 patients). The primary endpoint was a composite of all-cause mortality, unplanned cardiac surgery, clinically evident embolic events, or relapse of bacteremia with the primary pathogen. During the 6-month follow-up, the primary endpoint occurred in 9.0% of the oral group and 12.1% of the IV group, meeting the noninferiority criteria (P=0.40). All-cause mortality was numerically but not significantly lower in the oral group as compared with the IV group (3.5% vs 6.5%; HR, 0.53; 95% CI, 0.21 to 1.32). The oral group and IV group had a similar incidence of unplanned cardiac surgery (3.0%), embolic events (1.5%), and relapse of bacteremia (2.5%). The primary outcome was consistent across subgroups predefined by age, gender, bacteria type, valve type (native or prosthetic valve), and the affected valve (aortic or mitral valve). Adverse effects were uncommon and comparable between the two treatment groups (5% vs 6%; P=0.66). Although the median treatment duration was comparable (17 vs 19 days; P=0.48), the median length of hospital stay after randomization was 3 days (interquartile range, 1 to 10) in the oral group and 19 days (interquartile range, 14 to 25) in the IV group (P<0.001).

The study was limited by including only left-sided IE and excluding 25 to 30% of patients with culture-negative endocarditis or endocarditis caused by bacteria other than Streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. “Only five IV drug users were enrolled, only 22% of the enrolled patients had Staphylococcus aureus, and no patients with methicillin-resistant S. aureus or other antibiotic-resistant phenotypes were enrolled,” Iversen and colleagues further addressed in their paper. The findings may not be generalized to countries or regions with a high prevalence of antibiotic resistance. Shifting to oral antibiotics during half the treatment period was as effective and safe as continued IV antibiotics for stabilized patients with left-sided endocarditis, the authors concluded.