How do you determine the duration of antibiotic therapy in a patient with culture-negative native valve endocarditis who is clinically improving but has no identified organism to guide treatment?

I feel like any time I run into unique endocarditis questions, I'm back in the 2015 guidelines (Baddour et al., PMID 26373316). I do think that this is one of the lingering questions that is not fully answered in the guidelines, however--they are from 2015, and medical science has come a long way. The very helpful update to the Duke Criteria with the ISCVID working group (Fowler et al., PMID 37138445) helps shed some light on diagnostics that reduce the unlikely occurrence of culture negativity--namely Karius, which is not a test I use lightly due to various pros/cons, but can be applied in this situation. I've had a few come back positive for the harder-to-grow HACEK organisms or also Brucella/Bartonella. Additionally, I've had it be helpf...

Since endocarditis with negative cultures can occur because of prior antibiotic administration, I would give a 6-week course to ensure adequate coverage. This is a good review article on culture-negative endocarditis from the Journal of the American Heart Association. DeSimone et al., PMID 40094211