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

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.

Descriptive analysis evaluating the use of direct oral anticoagulation therapy in heart and lung transplant recipients.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely utilized following cardiothoracic transplantation with limited guidance regarding drug-drug interactions (DDIs), periprocedural management, and DOAC-specific monitoring. METHODS: We performed a single-center, retrospective, descriptive analysis of adult cardiothoracic transplant recipients initiated on DOAC therapy between May 2016 and July 2021. The primary endpoint for this analysis was the percentage of patients dosed per package labeling. Secondary endpoints included DOAC prescribing in the context of DDIs, renal dysfunction, and periprocedural management, as well as thromboembolism and major bleeding at 12 months. RESULTS: A total of 125 patients were included in this analysis with a median age of 62 years. At initiation, 63.2% of patients were dosed according to package labeling. The most common reason for non-labeled dosing was concomitant azole antifungal therapy. DOAC therapy was held for 82 procedures with no reported thrombotic events and one major bleed in the setting of AKI. Hemodialysis-dependence was associated with a reduced risk of thrombosis (0 vs. 10 events per 100 PY, p = .002) and an increased risk of major bleeding (23 vs. 8 events per 100 PY, p = .006). Additionally, DOAC-specific anti-xa guided dosing was associated with a reduced risk of major bleeding (0 vs. 13 events per 100 PY, p < .001). CONCLUSION: Our findings show that deviation from package labeling is common following cardiothoracic transplantation and its association with clinical outcomes warrants further study.

Real-world Assessment of 2879 COVID-19 Patients Treated With Monoclonal Antibody Therapy: A Propensity Score-Matched Cohort Study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally and cause significant morbidity and mortality. Antispike protein monoclonal antibody (mAb) therapy has been shown to prevent progression to severe coronavirus disease 2019 (COVID-19). The objective of this study was to report the outcomes of high-risk, SARS-CoV-2-positive patients infused with 1 of the 3 mAb therapies available through Food and Drug Administration Emergency Use Authorization (EUA). Methods: A total of 4328 SARS-CoV-2-positive patients who satisfied EUA criteria for eligibility for receiving mAb therapy were infused with bamlanivimab or the combination therapies bamlanivimab-etesevimab or casirivimab-imdevimab from November 22, 2020, to May 31, 2021, at 6 infusion clinics and multiple emergency departments within the 8 Houston Methodist Hospitals in Houston, Texas. The primary outcome of hospital admission within 14 and 28 days postinfusion was assessed relative to a propensity score-matched cohort, matched based on age, race/ethnicity, median income by zip code, body mass index, comorbidities, and positive polymerase chain reaction date. Secondary outcomes included intensive care unit admission and mortality. Results: A total of 2879 infused patients and matched controls were included in the analysis, including 1718 patients infused with bamlanivimab, 346 patients infused with bamlanivimab-etesevimab, and 815 patients infused with casirivimab-imdevimab. Hospital admission and mortality rates were significantly decreased overall in mAb-infused patients relative to matched controls. Among the infused cohort, those who received casirivimab-imdevimab had a significantly decreased rate of admission relative to the other 2 mAb therapy groups (adjusted risk ratio,0.51; P=.001). Conclusions: Treatment with bamlanivimab, bamlanivimab-etesevimab, or casirivimab-imdevimab significantly decreased the number of patients who progressed to severe COVID-19 disease and required hospitalization.

Clinical Outcomes Following Tocilizumab Administration in Mechanically Ventilated Coronavirus Disease 2019 Patients.

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.