Rivera, Christina G.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) practice has continued to increase. We sought to understand current OPAT practices in a survey of U. S. clinicians.Figure 1Respondents rated their agreement with the following statement: “The OPAT program at my hospital receives adequate support in the following areas”Figure 2Factors present in providing safe OPAT services on a scale where 1 is “extremely challenging” and 5 is “not challenging at all” Methods A survey instrument was developed by ID physicians, pharmacists and Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) staff, utilizing prior EIN OPAT surveys. The survey focused on respondents’ role, responsibilities, time devoted to OPAT, structure of OPAT provision, location where OPAT is received, institutional support and oversight, role of complex outpatient antimicrobial therapy (COpAT) including oral antimicrobials and long-acting injectable agents, and barriers to safe OPAT care. The confidential survey was distributed to adult EIN members from Feb to March 2025. Results Overall, 622 (38%) EIN members responded to the survey, of whom 469 with a role in managing OPAT patients were eligible to complete the survey. OPAT teams varied across programs with nearly all involving ID physicians (98%), majority involving ID/OPAT pharmacists (61%), nurses (60%), and nearly half involving administrative staff (48%) and advanced practice providers (APPs, 47%). ID consultation for OPAT enrollment was required in 60% of programs. Many programs (59%) report including COpAT. Response to outpatient lab results was largely managed by ID physicians (75%); however, multidisciplinary OPAT teams (37%), pharmacists (33%), and inpatient ID physicians (30%) were also frequently involved. Lab values were most often available via fax/email (43%) or electronic health record (EHR, 41%). Nearly 25% of programs “often/always” required proactive outreach to obtain safety labs. Overall, many programs lacked data analysis, administrative, information technology, and financial support (Figure 1). Challenges faced by OPAT programs included lack of leadership awareness of the value of OPAT (51%), difficulty managing patients with substance use disorder (50%), access to timely lab values (48%), personnel to retrieve missing lab values (46%), and struggles with the EHR (43%) (Figure 2). Conclusion Compared to EIN OPAT surveys in 2013 and 2019, programs have grown in size and composition, and expanded to COpAT. Similar problems persist regarding perceived lack of support. Disclosures Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, gsk: Advisor/Consultant|seqirus: Advisor/Consultant Philip M. Polgreen, MD, Eli Lily: Advisor/Consultant|Pfizer: Grant/Research Support Sara C. Keller, MD, MPH, MSPH, CorMedix: Grant/Research Support

Abstract Background According to consensus guidelines, area under the concentration–time curve (AUC) is recommended for vancomycin dosing rather than trough-based monitoring, but transition to AUC-based dosing requires substantial staff education and resource allocation. We sought to evaluate the level of congruency between vancomycin total daily doses (TDD) determined using a trough concentration goal of 10-15 mcg/mL compared with an online Bayesian calculator targeting an AUC of 400-600 mg·h/L.Patient DemographicsInitial Dose Results Methods We performed a retrospective, multicenter cohort study of vancomycin therapeutic drug monitoring (TDM) in non–critically ill adults hospitalized from March 1, 2017-December 31, 2021. Patients were included if they received intravenous vancomycin for ≥72 hours with a documented trough target of 10 to 15 mg/L, had ≥1 serum vancomycin trough concentration assessed at steady state, and received ≥2 doses of vancomycin after serum assessment with or without dose adjustment. Using an online vancomycin calculator with Bayesian modeling, the study team input patients’ trough-based dosing data to retrospectively estimate the initial vancomycin AUC exposure achieved and the initial and post-trough TDD recommended for an AUC target of 400 to 600 mg⸱h/L. The initial and post-trough vancomycin total daily dose (TDD) derived by the online calculator were compared with the actual doses used for each patient when a trough concentration of 10 to 15 mg/L was targeted.Comparison of Trough-Based and AUC-Based Dosing of Vancomycin AUC indicates area under the concentration–time curve; TDD, total daily dose. Dashed line indicates where the 2 methods are equal; shading indicates where the 2 methods are within 20% of each other Results In total, 89 patients were included in the study. The actual vancomycin TDD with trough monitoring (target, 10-15 mg/L) was within 20% of the recommended AUC-based TDD for 62 patients (70%) with initial dosing and for 74 (83%) after the initial trough concentration. Nephrotoxicity was rarely observed (2%) and the median duration of vancomycin was 4 days. Conclusion Given the frequency of dosing similarity between 400-600 mg·h/L AUC and 10-15 mg/L trough-based dosing, vancomycin trough-based monitoring to a goal of 10-15 mg/L is an option warranting further exploration. Disclosures All Authors: No reported disclosures

Abstract Background Beta-lactam pharmacokinetics can be significantly altered in patients with malignancy. Therapeutic drug monitoring (TDM; i.e., drug level testing) may facilitate pharmacokinetic/pharmacodynamic (PK/PD) target attainment, but the data are limited. This study aimed to characterize PK/PD target attainment of anti-pseudomonal beta-lactams in hematology/oncology patients.Table 1:Case DescriptionGraph 1:Distribution of Beta-Lactam TDM Indications Methods We conducted a retrospective review of beta-lactam TDM performed between June 2022 and June 2024 in hospitalized adults with hematologic or solid organ malignancies. We included patients who underwent beta-lactam TDM during clinical care, typically for extracorporeal membrane oxygenation (ECMO), extremes of body weight, suspected augmented renal clearance, multidrug-resistant infection, or suspected dose-dependent beta-lactam toxicity. Primary outcomes were (1) the proportion achieving target beta-lactam concentrations and (2) the proportion undergoing antibiotic dose adjustment based on TDM results.Table 2:Institutional Dosing Guidelines Results There were 47 TDM episodes in 20 unique patients. Considering only the first TDM per patient, 10 (50%) patients achieved target concentrations, 2 (10%) were below target, and 6 (30%) were above target. Antibiotic dose adjustments were made in 8 (40%) patients in response to TDM results. The most common indication for beta-lactam TDM was concerns regarding accurate renal clearance, followed by extremes of weight. Conclusion Retrospective findings suggest that beta-lactam TDM facilitated individualization of therapy in 40% of patients with either hematological or solid organ malignancy, with dose adjustments often intended to improve antibiotic safety. Future studies should refine the criteria for beta-lactam TDM use in this population and determine the need for tailored PK/PD targets in patients with impaired host response to infection. Disclosures All Authors: No reported disclosures

Abstract Background Antimicrobial stewardship programs (ASP) commonly employ formulary restriction and prospective audit with feedback; however, frontline prescribers and other unit-based clinicians may enhance core ASP tactics as ASP extenders. We hypothesized that unit-based pharmacists act as ASP extenders and sought to characterize ASP interventions in their routine work.Top individual antimicrobial classes intervened on by unit-based pharmacistsUnit-based pharmacist antimicrobial intervention types Methods Retrospective, observational study of ASP interventions by unit-based pharmacists from July 2017 - April 2025 across the Mayo Clinic Enterprise. ASP interventions recorded using a standardized pharmacist documentation tool (Epic iVents [Software]) were collected retrospectively. Interventions on hospitalized, adult patients categorized as ‘ASP’ or linked with an antimicrobial were included; interventions by ASP dedicated staff were excluded. Secondary outcomes included: intervention subtypes and outcomes, location, and associated antimicrobial(s). Frequencies and percentages were used to summarize categorical data. Results A total of 104,055 interventions were included from 59,106 unique patients at 26 hospitals with the majority performed at the three destination sites. On average, 1,107 interventions were completed monthly by unit-based pharmacists. Frequently targeted antimicrobial classes were vancomycin and derivatives, penicillins, and 3rd/4th-generation cephalosporins (e.g., ceftriaxone and cefepime) (Figure 1); 20,111 (19.3%) interventions were on ≥ 1 antimicrobial. Of the 66,827 interventions with a documented subtype, ASP was the most common (77.8%), with the remainder classified as dose (17.3%), medication (3%), or duration changes (1%) (Figure 2). A minority (2.2%) were documented as conducted under pharmacist collaborative practice agreements. Documented prescriber intervention rejections were uncommon (6.6%). Reported outcomes, when available, included therapy optimization, cost savings and avoidance of adverse drug events. Conclusion Unit-based pharmacists acted frequently as ASP extenders. These findings support unit-based pharmacist and ASP collaborative efforts. Disclosures All Authors: No reported disclosures

Abstract Purpose No consistent recommendations exist on how best to educate pharmacists to facilitate implementation of new evidence-based practices. This study aimed to determine whether spaced learning was more effective than traditional education when learning a new evidence-based practice (β-lactam therapeutic drug monitoring, or TDM). Summary β-lactam TDM was implemented in a phased fashion at Mayo Clinic in Rochester. Two go-lives took place, separated by 6 months, which allowed for a natural experiment to test education delivery methods (traditional education in the first go-live group of pharmacists vs spaced learning in the second go-live group of pharmacists). Each group received the same base educational package, with pharmacists in the spaced learning group also offered monthly in-person sessions for 6 months before go-live to discuss key considerations and cases with experts. There was no difference between the spaced learning group and the traditional education group when assessing appropriate use of TDM as defined by (1) appropriate patient selection; (2) correct ordering of laboratory testing; (3) appropriate clinical action; and (4) completed documentation. Assessments of secondary knowledge transfer also showed no difference between the groups. Pharmacists in the different education groups had similar satisfaction scores related to the effect and utility of the education. Both spaced learning and traditional education were part of a comprehensive implementation plan for β-lactam TDM, which might have influenced the outcomes. Spaced learning for future pharmacist education efforts needs further study. Conclusion As part of a greater β-lactam TDM implementation effort, altering the education delivery method did not impact the degree of knowledge transfer.

This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2–5] vs. EI 4 [3–5]; p = 0.22 and post: TD 3 [2–4] vs. EI 4 [3–5]; p = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.

Abstract Purpose Data regarding the incidence, onset, and management of complex outpatient antimicrobial therapy–induced neutropenia (COIN) are limited, and pharmacist involvement in COIN management has not been reported. This report describes the incidence, onset, and management of COIN at a large academic medical center. Methods This multisite retrospective cohort study examined adult patients undergoing serum laboratory monitoring for antimicrobials over a 4-year period. Patients receiving chemotherapy or immunosuppressants were excluded. Data collected included the antimicrobial regimen, complete blood count, duration of antimicrobial therapy until outcome occurrence, infectious syndrome, type of intervention, outcome, and pharmacist involvement. Logistic regression was used to assess risk factors for COIN incidence. The primary outcome was the incidence of COIN by antimicrobial drug. Results From 4,261 treatment episodes, 161 cases of COIN were identified (3.8% COIN incidence). The most common antimicrobials associated with COIN were intravenous piperacillin/tazobactam, cefepime, and meropenem. The majority of COIN events were attributed to a combination of at least 2 antimicrobials. Piperacillin/tazobactam was significantly associated with higher odds of developing COIN (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.04-3.34; P = 0.038), whereas ertapenem was associated with significantly lower odds of COIN (OR, 0.43; 95% CI, 0.24-0.77; P = 0.005). The median time to neutropenia diagnosis was 22 days (interquartile range, 14-29 days) from the time of inpatient antimicrobial start. Intervention for COIN occurred in 66.5% of cases, with neutrophil count recovering in 96.9% of these patients. Clinical pharmacists initiated 74.8% of interventions. Conclusion COIN can be effectively identified and managed by a multidisciplinary team reviewing routine laboratory monitoring, enabling most patients to safely complete antimicrobial treatment.

Abstract Background With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir, a broad-spectrum antiviral. Given the evolving nature of coronavirus disease 2019, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review with meta-analysis to summarize the effectiveness of remdesivir among hospitalized adults. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. Results From January 2019 to December 2023 >18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55–.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75–.88]), low-flow oxygen (0.71 [.64–.79]), high-flow oxygen (0.87 [.83–.91]), and invasive mechanical ventilation (0.78 [.68–.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64–.81]). Conclusions Our comprehensive systematic literature review, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection and receiving remdesivir, across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.

Abstract Reducing antimicrobial exposure by limiting the duration of therapy is an effective antimicrobial stewardship strategy. In this article, we describe the impact of modification of the electronic health record to remove default durations of therapy on ambulatory antibiotic prescriptions issued from emergency departments in a large, multicenter health system.