Objectives 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 aim 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 that 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, majority of patients 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 did not reach statistical significance (12.3% vs. 7.7%, P = 0.21). 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 = 0.07). 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.

Background Ceftriaxone (CRO) is a third-generation cephalosporin that is commonly prescribed due to its robust Gram-negative activity and lack of renal dose adjustments. It is also highly protein bound allowing for once daily dosing. In patients with hypoalbuminemia, however, the proportion of free drug is increased thus increasing the rate at which CRO is renally eliminated. This increased clearance could lead to lower serum concentrations and increased risk of treatment failure. Methods We performed a retrospective, cohort study to assess the impact of hypoalbuminemia (serum albumin ≤ 2.5 g/dL) on treatment failure among patients with monomicrobial Enterobacterales bacteremia. Adult patients who received > 72 hours of CRO therapy for susceptible Enterobacterales bacteremia between May 1, 2016 and April 30, 2021 were eligible for inclusion. The primary outcome of treatment failure was a composite of inpatient mortality or escalation to an intravenous anti-pseudomonal antibiotic or ertapenem. Secondary outcomes included hospital length of stay, total duration of antibiotic therapy, and time to infection resolution. Baseline characteristics and outcomes were compared using R Studio (Version 4.1.0) in a 1:1 propensity-matched cohort. Results After propensity score matching, 142 patients were included in each study group. The most common organisms in our cohort were Escherichia coli (71.5%), Klebsiella pneumoniae (14.1%), and Proteus mirabilis (5.3%). The most frequently implicated source of infection was the urinary tract (71.5%). Interestingly, treatment failure was numerically higher in the hypoalbuminemia group but was not statistically significant (12.0% vs. 7.7%, p = 0.23). All secondary outcomes were similar between groups. Among the subgroup of patients admitted to the ICU at baseline, the difference in treatment failure was even greater between patients with hypoalbuminemia and those without (23.3% vs. 7.5%, P = 0.07). Conclusion Hypoalbuminemia did not appear to have a significant impact on clinical outcomes among patients with Enterobacterales bacteremia treated with CRO. However, critically ill patients may be subject to higher incidence of treatment failure in the presence of hypoalbuminemia. Disclosures All Authors: No reported disclosures.