Abstract

Abstract Background The threat of inducible resistance and treatment failure positioned cefepime and carbapenems as the standard of care (SOC) treatment agents for infections due to AmpC-producing Enterobacterales regardless of antimicrobial susceptibility testing results. Recently published Infectious Diseases Society of America Guidance (IDSA) classifies the overall risk of clinically relevant AmpC expression for Serratia marcescens as low (< 5%). We aimed to compare the clinical outcomes of patients treated with a SOC antibiotic (carbapenem or cefepime) to those treated with an alternative beta-lactam agent for S. marcescens bloodstream infection (BSI). Methods This multisite, retrospective study included patients from five hospitals in the Atlanta-Metropolitan area with S. marcescens BSIs between January 1, 2018 and December 31, 2022. Patients were included if they received at least 72 hours of therapy with a beta-lactam antibiotic whose in vitro susceptibility was confirmed. Patients with polymicrobial bacteremia, those receiving combination therapy for > 72 hours, or those with a diagnosis of endovascular infection were excluded. We used a desirability of outcome ranking (DOOR) analysis to determine the probability of having a more desirable outcome receiving SOC antibiotics compared to receiving an alternative beta-lactam agent. The DOOR analysis includes counting undesirable events (Figure 1) and was performed using an online calculator (https://methods.bsc.gwu.edu).Figure 1:Primary endpoint - Desirability of outcome ranking. Abbreviations: AKI = acute kidney injury; CDI = Clostridioides difficile infection; EMR = electronic medical record; SCr = serum creatinine Results Of the 175 S. marcescens blood cultures reviewed, 66 patients met criteria for study inclusion, 43 in the SOC group and 23 in the alternative group. Baseline characteristics were comparable in both groups (Figure 2). The DOOR distribution between treatment groups was similar (Figure 3) and there was no significant difference in the probability of a more desirable outcome for patients who received an alternative beta-lactam compared to SOC (54.2% [95% CI, 40.3 - 67.5%]; Figure 4).Figure 2:Baseline patient characteristics. Abbreviations: BMT = bone marrow transplant within previous 12 months; Corticosteroid = ≥15 mg prednisolone daily equivalents; HIV = human immunodeficiency virus; ICU = intensive care unit; IQR = interquartile range; NS = non-significant; SOC = standard of care; SOT = any history of solid organ transplantFigure 3:Desirability of Outcome Ranking Distribution Summary Desirability of outcome ranking distribution for the standard of care and alternative beta-lactam treatment groups; SOC = standard of careFigure 4:Desirability of Outcome Ranking Probability Summary Forest plot of desirability of outcome ranking probabilities by overall treatment group and individual ranking components; CI = confidence interval, DOOR = desirability of outcome ranking, SOC = standard of care Conclusion The overall outcome of patients receiving alternative beta-lactam antibiotics was similar to those receiving SOC antibiotics in this study. These results support use of alternative beta-lactams for treatment of susceptible S. marcescens BSIs as recommended by IDSA guidance. Disclosures Joseph Torrisi, PharmD, BCIDP, Clinical Care Operations: Honoraria Ahmed Babiker, MBBS, Roche: Advisor/Consultant

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