Reviewed by: David Cluck, PharmD; East Tennessee State University
The POET II investigators sought to evaluate whether a clinical response–tailored antibiotic management strategy can shorten treatment duration (by 2-3 weeks) without compromising safety in patients with left-sided infective endocarditis (IE).1 A total of 508 adult patients with (native or prosthetic valve) infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococcus species were randomized to receive either response-tailored or standard-duration antibiotic therapy. The study consisted of predominantly male patients (75%) with a mean age of 70 years. The aortic valve was affected in nearly two-thirds of patients (63.2%), and approximately one-quarter of the cohort (26.4%) had prosthetic-valve infective endocarditis. Before randomization, 168 patients (33.1%) had undergone cardiac surgery, including 40 patients (23.8%) with prosthetic-valve infective endocarditis. The most common bacterial pathogen in the study was streptococcus species (57%). Prior to randomization, all patients received at least 2 to 4 weeks of therapy and met criteria for clinical stabilization. After randomization, patients in the tailored-therapy group discontinued antibiotics whereas those in the standard-therapy group continued standard treatment for a total of 4-6 weeks. The primary efficacy end point was days alive without antibiotic treatment for infective endocarditis or bacteremia within 6 months after randomization. The primary safety end point was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months after randomization. The median time alive without antibiotic treatment was 183 days (interquartile range, 181 to 183) with tailored therapy and 169 days (interquartile range, 166 to 171) with standard therapy (Hodges– Lehmann estimated difference, 13 days; 95% confidence interval [CI], 12 to 13; P<0.001 for superiority). A primary safety end-point event occurred in 21 patients (8.2%) with tailored therapy and in 27 patients (10.7%) with standard therapy (absolute between-group difference, −2.4 percentage points; 95% CI, −7.7 to 2.7; P<0.001 for noninferiority). Perhaps most importantly relapse occurred in 13 patients (5.1%) with tailored therapy and in 4 patients (1.6%) with standard therapy (P = 0.04) with the highest risk associated with Enterococcal IE.
Bottom Line: This study demonstrated that shorter durations of antibiotic therapy may be appropriate to treat left-sided IE without compromising patient safety in select patients. Notably, this study integrated findings from the original POET study supporting use of oral antimicrobial therapy in patients with IE.2 The study however does have important limitations including a low number of enrolled patients with methicillin-resistant Staphylococcus aureus (if any) as well as a low number of patients with substance use disorder. It is also important to note that although the investigators set out to examine the reduction in length of duration of antibiotic therapy, the primary efficacy outcome was modified during the study to number of days alive without antibiotic treatment or bacteremia.
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