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The POET study (NEJM JW Infect Dis Oct 2018 and N Engl J Med 2019; 380:415) challenged the dogma that endocarditis must be treated exclusively with intravenous (IV) antibiotics. This landmark study showed that in patients with left-sided staphylococcal, streptococcal, or enterococcal endocarditis, a switch to oral, outpatient antibiotic treatment was noninferior to continued IV treatment, provided patients were in stable condition after at least 10 days of IV therapy and oral medication could be taken. In the original study, outcomes were assessed 6 months after the end of therapy. How did these patients fare later on?
The POET researchers have now published updated outcomes of their original study with a median follow-up of 3.5 years. For this post hoc analysis, none of the 400 enrolled patients was lost to follow-up. Significantly more patients randomized to continuous IV treatment than to oral treatment met the composite endpoint of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen (38% vs. 26%; hazard ratio, 0.64). Mortality was 27% and 16%, respectively (hazard ratio, 0.57). Rates of cardiovascular deaths and deaths due to cancer were higher in the continuously IV-treated group, but relapse of infection and infection-related deaths did not differ significantly between the groups.
Bundgaard H et al. Long-term outcomes of partial oral treatment of endocarditis. N Engl J Med 2019 Mar 17; [e-pub]. (https://doi.org/10.1056/NEJMc1902096)
Comment
The significant mortality difference between the two treatment groups is unlikely to be causally related to the mode of antibiotic administration. This difference is better explained by residual imbalances in comorbidities of the study population, despite randomization. However, it is reassuring that switching patients with stable endocarditis from IV to early oral antibiotic treatment was not associated with delayed treatment failure. Since the publication of the POET study, I have successfully treated several patients with partial oral antibiotic treatment according to the POET study protocol — but those not meeting these criteria I kept on continued IV therapy.