Literature
Clinical Pearls & Morning Reports
Published January 30, 2019
In patients with left-sided endocarditis, is a shift to oral antibiotics after an initial course of intravenous antibiotics noninferior to continuous intravenous antibiotic treatment?
Intravenous treatment during long hospital stays may be associated with an increased risk of complications, whereas a shorter length of hospital stay has been associated with better outcomes in studies of other diseases. Iversen et al. conducted a noninferiority trial to assess whether in clinically stable patients who have endocarditis on the left side of the heart, a shift from intravenously to orally administered antibiotic treatment would result in efficacy and safety that would be similar to those with continued intravenous antibiotic treatment. Read the NEJM Original Article here.
Clinical Pearls
Q: What were some of the eligibility criteria for the trial by Iversen et al.?
A: Eligible patients were adults, 18 years of age or older, in stable condition who were receiving intravenous antibiotic treatment for endocarditis on the left side of the heart (on native or prosthetic valves), who fulfilled the modified Duke criteria, and who had blood cultures that were positive for streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci.
Q: In patients with left-sided endocarditis, is a shift to oral antibiotics after an initial course of intravenous antibiotics noninferior to continuous intravenous antibiotic treatment?
A: In the trial by Iversen et al., the primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, clinically evident embolic events, or relapse of bacteremia with the primary pathogen (detected in blood cultures obtained during follow-up or for clinical reasons) from randomization through 6 months after antibiotic treatment was completed. The primary composite outcome occurred in a total of 42 patients (10.5%) — in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (odds ratio, 0.72; 95% confidence interval [CI], 0.37 to 1.36). The between-group difference was 3.1 percentage points (95% CI, –3.4 to 9.6; P=0.40) in favor of oral treatment, and the criterion for noninferiority was therefore met.
Morning Report Questions
Q: In the trial by Iversen et al., did the successful transition to oral antibiotics depend on the pathogen involved?
A: The results seemed consistent across prespecified subgroups, including the subgroups defined according to type of valve affected (native valve or prosthetic valve) and according to type of treatment (surgery during the disease course or conservative treatment). It should also be noted that the primary outcome seemed similar across the four different bacterial types. However, the trial was not powered to assess the primary outcome in any of the prespecified subgroups.
Q: How generalizable are the findings of the trial by Iversen et al.?
A: Only patients with endocarditis caused by certain bacterial species were eligible, and the results may not apply to the remaining 25 to 30% of patients who have endocarditis caused by other bacteria or to patients with culture-negative endocarditis. In addition, only five intravenous drug users were enrolled, only 22% of the enrolled patients had S. aureus, and, although it was not a criterion for exclusion, no patients with methicillin-resistant S. aureus or other antibiotic-resistant phenotypes were enrolled.