Impact of Hypoalbuminemia on Ceftriaxone Treatment Failure in Patients With Enterobacterales Bacteremia: A Propensity-Matched, Retrospective Cohort Study

Abstract Background Ceftriaxone is frequently prescribed due to its convenience of dosing and robust antimicrobial activity. However, patients with hypoalbuminemia may experience suboptimal ceftriaxone exposure due to the high degree of protein binding. We aimed to evaluate the impact of hypoalbuminemia on treatment failure among hospitalized adults with Enterobacterales bacteremia who received ceftriaxone therapy. Methods We conducted an observational cohort study among patients with Enterobacterales bacteremia who received >72 hours of ceftriaxone initiated within 48 hours of index culture. A propensity-score model was used to match and compare patients with hypoalbuminemia. The primary outcome was treatment failure, defined as a composite of (1) escalation from ceftriaxone to ertapenem or an intravenous antibacterial agent with activity against Pseudomonas aeruginosa, or (2) inpatient death. Secondary outcomes included hospital length of stay, duration of antibiotic therapy, and time to infection resolution. Results Of 260 patients included, the majority developed bacteremia from a urinary source (71.5%), and Escherichia coli was the most common pathogen identified (72.3%). Patients with hypoalbuminemia experienced numerically higher rates of treatment failure, although not reaching statistical significance (12.3% vs 7.7%; P = .21). Among patients receiving care in the intensive care unit, the impact of hypoalbuminemia on treatment failure was more pronounced (24.4% vs 7.3%; P = .07). Conclusions Hypoalbuminemia may not have a significant impact on clinical outcomes among patients with Enterobacterales bacteremia treated with ceftriaxone. However, critically ill patients may be subject to higher incidence of treatment failure in the presence of hypoalbuminemia. Patients with hypoalbuminemia may experience suboptimal ceftriaxone exposure due to high protein binding. A matched cohort of patients with Enterobacterales bacteremia treated with ceftriaxone did not show a significant difference in treatment failure between the normoalbuminemia or hypoalbuminemia groups.