Duration of Antibiotic Therapy for Uncomplicated Gram-Negative Bacteremia in Solid Organ Transplantation

Abstract Background We hypothesize that short durations (≤10 days) of antibiotics for uncomplicated gram-negative bacteremia (GNB) would have similar clinical outcomes compared to long durations ( 10 days) in solid organ transplant (SOT) patients. DOOR Probability Forest PlotFigure 1.Forest plot demonstrating the desirability of outcome ranking (DOOR) probabilities for each individual DOOR component (survival without adverse events, microbiologic failure, isolation of an MDR gram-negative in the blood, C. difficile infection or death) as well as the overall DOOR probability of having a more desirable outcome with 10 days versus ≥10 days of antimicrobial treatment. Methods A retrospective cohort review was conducted on patients admitted to University of Maryland Medical System hospitals from 1/1/2019 to 6/30/2024. Included patients were ≥18 years old with an uncomplicated GNB defined as a confirmed Enterobacterales bacteremia, source control, and clinical stability at 72 hours. The primary outcome was a Desirability of Outcome Ranking (DOOR) comparison between 10 days versus ≥10 days of treatment. Each patient was assigned a DOOR rank from 1 (survival without adverse events) to 5 (death). Ranks 2-4 included patients who survived but had 1, 2, or 3 undesirable events occur during the 30-day follow-up period, respectively. Undesirable events included microbiologic failure, isolation of an MDR gram-negative in the blood, or C. difficile infection. Confidence intervals for the DOOR probability were calculated using the Halperin et al. (1989) method with a 95% confidence level, with a statistically significant two-sided p-value of 0.05. Results A total of 105 patients were included in this study, with 27 patients in 10 day cohort and 78 patients in the ≥10 day cohort. The source of GNB was significantly different between groups (p=0.007), with the 10 day cohort having more intrabdominal infections (48.2% vs 19.2%) and the ≥ 10 cohort having more urinary sources of infection (67.9% vs 37.0%). There were more patients with an oral switch in the ≥10 day treatment cohort (66.7% vs 33.3%, p=0.003). The overall DOOR probability of having a more favorable outcome with a treatment duration of 10 days compared to ≥10 day treatment was not statistically different (44.7%, 95% CI: 36.8%, 52.9%; p = 0.1235), highlighting that longer durations of therapy were not associated with improved outcomes. Conclusion In patients with a solid organ transplant and uncomplicated GNB, there was no significant difference in outcomes when treated for 10 days or ≥ 10 days. Further studies with larger sample sizes are needed to highlight the efficacy and safety of shorter antibiotic durations for uncomplicated GNB in solid organ transplantation. Disclosures Emily L. Heil, PharmD, MS, Wolters-Kluwer: Advisor/Consultant