Rivera, Christina G

ABSTRACT The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m 2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) ( P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

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A commentary on Canterino et al. (2024) and Munsiff et al. (2024), articles where clinicians from two large OPAT programs

AbstractBeta‐lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta‐lactam TDM program. This single‐center experience forms the basis of the manuscript which outlines practical considerations involved with beta‐lactam TDM implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist‐led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of ‘individual internalization’ seems to be uniquely important to beta‐lactam TDM implementation compared with the implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist‐led beta‐lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program.

Abstract Outpatient parenteral antimicrobial therapy (OPAT) has become more common in clinical settings. Correspondingly, OPAT-related publications have also increased; the objective of this article was to summarize clinically meaningful OPAT-related publications in 2022. Seventy-five articles were initially identified, with 54 being scored. The top 20 OPAT articles published in 2022 were reviewed by a group of multidisciplinary OPAT clinicians. This article provides a summary of the “top 10” OPAT publications of 2022.

Abstract Introduction During the early phase of the coronavirus disease 2019 (COVID‐19), remdesivir was only approved for hospitalized patients. Our institution developed hospital‐based, outpatient infusion centers for selected hospitalized patients with COVID‐19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods Retrospective study of all hospitalized adult patients with COVID‐19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results Among 3029 hospitalized patients who received treatment with remdesivir for COVID‐19, the majority (89.5%) completed the recommended 5‐day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5‐day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001). Conclusions This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5‐day course of remdesivir.

Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals’ experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction of new antimicrobials and novel combinations are exciting developments but also further complicate IE treatment choices. In this review, we provide and evaluate the relevant evidence focused around contemporary debates in IE treatment pharmacotherapy, including beta-lactam choice in MSSA IE, combination therapies (aminoglycosides, ceftaroline), the use of oral antimicrobials, the role of rifamycins, and long-acting lipoglycopeptides.

AbstractBackgroundItraconazole is the recommended first‐line treatment for mild‐to‐moderate blastomycosis and consolidation treatment of moderate‐to‐severe disease. Itraconazole is metabolised into three metabolites, including an active metabolite hydroxy‐itraconazole. Literature provides little evidence indicating whether therapeutic drug monitoring targets should be based on itraconazole parent compound alone or a sum of itraconazole and hydroxy‐itraconazole serum concentrations.ObjectivesThis study aims to compare clinical outcomes and adverse drug events (ADEs) of combined itraconazole and hydroxy‐itraconazole concentrations versus itraconazole parent compound alone in patients with blastomycosis.Patients/MethodsThis study was a retrospective cohort review of patients ≥18 years with probable or proven Blastomyces infection who received itraconazole with at least one documented serum itraconazole concentration. The primary outcome was rate of partial or complete treatment response across three patient groups: (1) Itraconazole parent compound >1.0 mcg/ml (parent), (2) parent compound <1.0 mcg/ml, but a combined itraconazole and hydroxy‐itraconazole >1.0 mcg/ml (combined) and (3) failure to achieve a combined or parent concentration >1.0 mcg/ml (subtherapeutic) for >75% of the duration of itraconazole therapy.ResultsA total of 80 patients were included (parent = 32, combined = 36, subtherapeutic = 12). No statistically significant difference was observed for rate of partial or complete treatment response (97% parent vs 94% combined, p = .99). Significantly higher mortality due to blastomycosis was observed in patients in the subtherapeutic group (0% parent vs 3% combined vs 25% subtherapeutic, p = .01).ConclusionsThis study supports an itraconazole therapeutic target combining itraconazole and hydroxy‐itraconazole >1.0 mcg/ml for blastomycosis treatment.

AbstractPurposeVancomycin area under the concentration-time curve (AUC) can be calculated using steady-state serum peak and trough concentrations; however, compared to traditional trough-only monitoring, this approach requires an additional blood sample. Recently published data demonstrated vancomycin AUC estimations using trough-only data with a volume of distribution (Vd) model incorporating age and actual body weight were reasonably accurate and precise in a veteran population. This study sought to extend these methods to a Mayo Clinic adult population.MethodsA retrospective, observational cohort of adult patients with documented steady-state vancomycin peak and trough concentrations was evaluated. Vancomycin AUCs were estimated using trough-only data, and 4 Vd models were assessed for accuracy and precision. Estimated AUCs were compared to AUCs calculated using 1-compartment intermittent infusion equations and steady-state peak and trough (“peak-trough”) data.ResultsThe study population (N = 95) was 46% female, with a median age of 59 years and a median weight of 97 kg. Using the VancoPK equation Vd = 0.29 (age in y) + 0.33 (actual weight in kg) + 11, the mean peak-trough and estimated trough-only AUC were 533 and 534, respectively, with a correlation of 0.936. The root mean square error was 47.7, meaning about 95% of AUCs were within 95 mg · h/L of peak-trough AUCs.ConclusionsAccuracy and precision of Vancomycin AUC estimations using trough-only data and the described Vd model were demonstrated in a Mayo Clinic cohort. Targeting an estimated AUC of 500 mg · h/L using the VancoPK model would likely result in an actual AUC within 400 to 600 mg · h/L.