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BackgroundCeftriaxone 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.MethodsWe 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.ResultsOf 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).ConclusionsHypoalbuminemia 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.

Background Dalbavancin and oritavancin are long acting lipoglycopeptide antibiotics (LaLGP) approved for treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. These antibiotics have shown promise in treatment of non-FDA approved gram-positive infections including bacteremia, endocarditis, pneumonia, and osteomyelitis. The aim of this review was to determine indication, length of therapy, treatment failures, and adverse drug events (ADE) in patients receiving LaLGP at our institution. Methods Retrospective study of adult patients that received LaLGP within an integrated health system consisting of 3 hospitals and 2 outpatient infusion centers, between July 2016 and February 2022. Data collection included dosing regimen specifics for both LaLGP and non-LaLGP, indication and justification for LaLGP use, culture results, labs, ADE, incidence of readmission and Emergency (ED)/Urgent Care presentation, and treatment failure defined as readmission or return to the ED/Urgent care within 90 days of therapy completion. Results 36 patients received LaLGP during the study period. A majority of patients received LaLGP for an indication other than ABSSSI (64%)(Table 1). Four patients were lost to follow-up but included in analysis of indication and justification for LaLGP use. Staphylococcus aureus (30% MRSA, 26% MSSA) was the most commonly identified pathogen in patients who received LaLGP for non-ABSSSI indications. Justification for use of LaLGP over standard therapy is shown in Table 2. The median duration of standard therapy prior to transitioning to LaLGP was 7 days. Table 3 shows agent selection, number of doses, and outcomes for ABSSSI indications vs non-ABSSSI indications. ABSSSI patients received a maximum of 2 doses; non-ABSSSI indications received 1-8 doses. Re-admission rates were higher in the ABSSSI group compared to non-ABSSSI while ED/Urgent care presentations were higher in non-ABSSSI indications. Conclusion LaLGP is a viable option for therapy completion after improvement is seen while on standard therapy in patients where daily outpatient antimicrobial therapy is not feasible. While LaLGP is currently only approved for ABSSSI, they appear to be safe and effective for other indications. Disclosures All Authors: No reported disclosures.

Background Methods to operationalize antibiotic timeouts (ATO) among hospitalized patients are often constrained by the high volume of antibiotic orders that surpass the capabilities of the antimicrobial stewardship program (ASP) to intervene. Houston Methodist Hospital implemented a streamlined electronic ATO process that alerted providers to evaluate the need for continued antibiotics on day 4 of predefined anti-infective therapy. Unresolved alerts were reviewed by clinical pharmacists the following day. The objective of this study was to determine the impact of this electronic ATO on frequently prescribed antibiotics. Methods This was a quasi-experimental study in a 924-bed quaternary care hospital comparing days of therapy (DOT) in patients admitted prior to (February 2017 – January 2018) and after implementing an ATO process (March 2018 – February 2019). Antibiotics evaluated included vancomycin, cefepime, piperacillin/tazobactam, and meropenem. ATO alert logic was simulated retrospectively to capture the pre-ATO cohort. The primary outcome was mean composite DOT per patient admission. Secondary outcomes included total hospitalization cost, Clostridioides difficile infection (CDI) and multidrug-resistant organism (MDRO) rates. Results A total of 8,458 patients met ATO alert criteria for inclusion in the pre-ATO timeframe and 6,901 patients with an ATO alert in the post-ATO group; 2,642 (38%) prompted a pharmacists’ review. The average composite DOT was 11.5 per admission in the pre-ATO cohort compared with 11.1 in the post-ATO cohort (P = 0.02). After multivariate linear regression, the ATO was significantly associated with a decrease of 0.5 DOT per patient admission (P < 0.001). Other factors associated with a reduction in DOT included age (P < 0.001), service line (P = 0.003), and admission source (P = 0.031). Mean hospital costs per admission were significantly reduced in the post-ATO group: $67,613 vs. $66,615 (P = 0.01). There was no difference in rates of CDI and MDRO. Conclusion Implementation of our electronic ATO process demonstrated significant reductions in overall DOT for frequently prescribed antibiotics and decreased total hospital costs across a diverse patient population. This process provides a real-world strategy to operationalize a large-scale ATO as an adjunct to an ASP. Disclosures All authors: No reported disclosures.

Background Collaborations between medication safety and antimicrobial stewardship programs (ASP) have not been well described despite many overlapping best practice initiatives. In partnership with medication safety, the ASP at Houston Methodist (HM) reviews patient safety events submitted by hospital staff and identified a best practice opportunity in allergy reporting practices. Our objective was to benchmark self-reported antibiotic allergies among hospitalized patients and compare the prevalence and characteristics among hospital settings. Methods We evaluated the prevalence of self-reported antibiotic allergies in the electronic medical record for adult patients admitted to any HM entity including 1 flagship referral center (933-beds) and 6 community-based hospitals (1,379-beds) in January 2019. Antibiotics were grouped by class into penicillins, sulfas, cephalosporins, tetracyclines, macrolides, quinolones, and others. Point-prevalence rates were calculated using the total patient count as the denominator. Results There were 4,730 patients admitted to HM in January 2019 of which 85% (n = 4,029) self-reported 9,186 active drug allergies. There were 2,353 (49.7%) individuals who self-reported 3,665 antibiotic allergies, of which 987 (21%) reported an allergy to ≥2 antibiotic classes. The prevalence rate for a penicillin allergy was highest at 26.1% (n = 1,235), followed by allergy to sulfa 15.9% (n = 751) and quinolones 7.9% (n = 411). Antibiotic allergies were most prevalent in patients aged 70–79 (11%, n = 518) and 60–69 (10%, n = 495). Antibiotic allergies were higher among females (61.6%; n = 1,679/2,724) compared with males (40.7%; n = 662/1,305) (P = 0.002). There was no difference in prevalence rates between community-based hospitals and the flagship institution (P = 0.51). Conclusion We identified an antibiotic allergy point prevalence rate of 49.7% among hospitalized patients, including a 26.1% rate to penicillin, across our 7-hospital system. This analysis provides a road map to deploy system-wide efforts to improve antibiotic detailing in patients regardless of the hospital setting. Disclosures All authors: No reported disclosures.