A Desirability of Outcome Ranking Analysis of a Randomized Clinical Trial Comparing Seven Versus Fourteen Days of Antibiotics for Uncomplicated Gram-Negative Bloodstream Infection

Abstract

Background Although a short course (7 days) of antibiotics has been demonstrated to be non-inferior to a conventional course (14 days) in terms of mortality and infectious complications for patients with a Gram-negative bacterial bloodstream infection (GNB), it is unknown whether a shorter treatment duration can provide a better overall clinical outcome. Methods We applied a bloodstream infection-specific desirability of outcome ranking (DOOR) analysis to the results of a previously completed, randomized controlled trial comparing short versus conventional course antibiotic therapy for hospitalized patients with uncomplicated GNB. We determined the probability that a randomly selected participant in the short course group would have a more desirable overall outcome than a participant in the conventional duration group. We performed partial credit analyses allowing for calculated and variable weighting of DOOR ranks, and subgroup analyses to elucidate which patients may benefit the most from short durations of therapy. Results For the 604 patients included in the original study (306 short course, 298 conventional course), the probability of having a more desirable outcome with a short course of antibiotics compared to a conventional course was 51.1% (95% confidence interval 46.7% to 55.4%), indicating no significant difference. Partial credit analyses indicated that the DOOR results were similar across different patient preferences. Prespecified subgroup analyses using DOOR did not reveal significant differences between short and conventional courses of therapy. Conclusions Both short and conventional durations of antibiotic therapy provide comparable clinical outcomes when using DOOR to consider benefits and risks of treatment options for GNB.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study

“…Given the limited data for shorter durations of therapy when oral BLs are used, the 14-day duration of therapy used in our study may still be clinically applicable. In addition of total treatment duration, the average duration of IV therapy was comparable to other studies at approximately 5 days [17][18][19][20][21][22][23]28,30]. It is important to note that IV duration in our study was on average one day shorter in the FQ group (4 days vs. 5 days).…”

“…However, oral BLs were underrepresented in this study (< 20% of overall cohort), which limits the ability to apply these findings when oral BLs are used as stepdown therapy. A desirability of outcome ranking (DOOR) analysis including this study suggests that short course (7 days) of antibiotics has comparable clinical outcomes to conventional course (14 days) in this patient population [30]. Given the limited data for shorter durations of therapy when oral BLs are used, the 14-day duration of therapy used in our study may still be clinically applicable.…”

Significant Publications on Infectious Diseases Pharmacotherapy in 2022

“…Limitations of this study included minimal minority representation and lack of a pre-CDI-antibiotic stool specimen, which inhibited a full assessment of SER-109’s effect on the microbiome. Overall, this study showed SER-109 was superior in reducing CDI recurrence vs placebo and is a promising start for this new drug class in decreasing CDI burden in the US. Howard-Anderson J et al A Desirability of Outcome Ranking Analysis of Randomized Clinical Trial Comparing Seven vs Fourteen Days of Antibiotics for Uncomplicated Gram-Negative Bloodstream Infection 17 …”

“…The top 10 general ID and top 1 HIV/AIDS papers are summarized here in alphabetical order of the first author. 16-39 Chuang YC et al The combination of daptomycin with β-lactam antibiotics is more effective than daptomycin alone for vancomycin-resistant Enterococcus faecium bloodstream infection 25 …”

Desirability of outcome ranking and quality life measurement for antimicrobial research in organ transplantation

“…Many others have applied DOOR analysis retrospectively to previously performed clinical trials. [35][36][37][38] These analyses must work within the framework of data collected as part of the original trial and may be limited, especially in ability to measure patient-reported outcomes.…”