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Background: It is unknown whether ChatGPT provides quality responses to infectious diseases (ID) pharmacotherapy questions. This study surveyed ID pharmacist subject matter experts (SMEs) to assess the quality of ChatGPT version 3.5 (GPT-3.5) responses., Methods: The primary outcome was the percentage of GPT-3.5 responses considered useful by SME rating. Secondary outcomes were SMEs' ratings of correctness, completeness, and safety. Rating definitions were based on literature review. One hundred ID pharmacotherapy questions were entered into GPT-3.5 without custom instructions or additional prompts, and responses were recorded. A 0-10 rating scale for correctness, completeness, and safety was developed and validated for interrater reliability. Continuous and categorical variables were assessed for interrater reliability via average measures intraclass correlation coefficient and Fleiss multirater kappa, respectively. SMEs' responses were compared by the Kruskal-Wallis test and chi-square test for continuous and categorical variables., Results: SMEs considered 41.8% of responses useful. Median (IQR) ratings for correctness, completeness, and safety were 7 (4-9), 5 (3-8), and 8 (4-10), respectively. The Fleiss multirater kappa for usefulness was 0.379 (95% CI, .317-.441) indicating fair agreement, and intraclass correlation coefficients were 0.820 (95% CI, .758-.870), 0.745 (95% CI, .656-.816), and 0.833 (95% CI, .775-.880) for correctness, completeness, and safety, indicating at least substantial agreement. No significant difference was observed among SME responses for percentage of responses considered useful., Conclusions: Fewer than 50% of GPT-3.5 responses were considered useful by SMEs. Responses were mostly considered correct and safe but were often incomplete, suggesting that GPT-3.5 responses may not replace an ID pharmacist's responses., Competing Interests: Potential conflicts of interest. J. M. S. served on an advisory board for Paratek Pharmaceuticals. E. B. C. served on an advisory board and speakers bureau for Seqirus. W. D. K. received research grants from Melinta, Merck & Co, and Shionogi, Inc and served on an advisory board for Theratechnologies, Inc. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cefazolin is guideline recommended for perioperative prophylaxis in orthopedic surgery. Despite its unique R1 side chain, cefazolin is often avoided in patients with beta-lactam allergy with concern for cross reactivity. Objectives: The primary outcome was the percentage of patients who received cefazolin perioperatively. Secondary outcomes included the percentage of patients with a beta-lactam allergy clarified following the telephone interview and clinical outcomes including acute kidney injury, surgical site infection, Clostridioides difficile infection, and re-admission at 30 and 90 days. Methods: This single-center, quasi-experimental study evaluated a pilot program in which a pharmacist phoned patients > 18 years of age with a scheduled orthopedic surgery and a documented beta-lactam allergy to assess their allergy preoperatively. Recommendations to use cefazolin were based on an algorithm. Patients were divided into pre- and post-intervention cohorts. Results: A total of 832 patients were screened for inclusion with 135 and 66 patients included in the pre- and post-intervention cohorts. No significant difference was identified in the primary outcome. In the post-intervention cohort, 62% had a beta-lactam reaction updated in the electronic medical record. Those with a beta-lactam allergy delabeled or made less severe were numerically more likely to receive cefazolin than those with an unchanged reaction or a reaction made more severe (95.2% vs 68% vs 65%). There were no differences in clinical outcomes between groups. Conclusion: A pharmacist-conducted preoperative beta-lactam allergy interview in adult patients undergoing elective orthopedic surgery improved beta-lactam allergy documentation but, did not result in increased utilization of cefazolin., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Wesley D. Kufel has received research grants from Merck and Co. and Melinta Therapeutics and served on the advisory board for Theratechnologies. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Many Postgraduate Year One (PGY1) Pharmacy residencies provide research training however, details of this training are not well described. Publication rates have been utilized to assess residency research learning experiences. Higher publication rates have been reported by programs that have implemented a structured research learning experience. Objective: The primary objective was to identify differences in the research learning experiences for American Society of Health-System Pharmacists (ASHP) accredited PGY1 Pharmacy residencies with reported resident publication rates of ≥20% vs <20%. Methods: This survey was distributed to PGY1 Pharmacy residency program directors (RPDs). Seven sections were analyzed to identify research learning experience differences between programs with reported publication rates of ≥20% vs <20%: (1) program characteristics/research outcomes; (2) involved individuals; (3) requirements; (4) learning experience structure; (5) educational methods; (6) formal education; (7) barriers/RPD perceptions. Variables with P < 0.05 on logistic regression were considered statistically significant. Results: The survey response rate was 31.3% (308/984). Significant positive predictors for reported publication rates of ≥20% were: involved individuals: research director/coordinator, individuals trained in statistics, non-pharmacy medical staff; requirements: Collaborative Institutional Training Initiative training, research seminars/training courses, research manuscript; learning experience structure: research committee; educational methods: didactic residency-led lectures/courses, formal workshops, self-taught online modules; and formal education: manuscript preparation. Conclusion: This study suggests there are differences in the research learning experiences at PGY1 Pharmacy residencies with reported resident publications rates of ≥20% vs <20%. We encourage PGY1 Pharmacy residency programs to consider implementing elements associated with reported resident publication rates of ≥20%., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The objective of this project was to assess the percentage of interoperability compliance within our pediatric hematology/oncology patient care areas for intravenous chemotherapy medications before and after the implementation of circle priming., Methods: We conducted a retrospective quality improvement project at an inpatient pediatric hematology/oncology floor and outpatient pediatric infusion center before and after implementation of circle priming., Results: There was a statistically significant increase in percent interoperability compliance for the inpatient pediatric hematology/oncology floor from 4.1% prior to implementation of circle priming to 35.6% after (odds ratio 13.1 (95% CI, 3.96-43.1), p  < 0.001), as well as for the outpatient pediatric infusion center from 18.5% to 47.3%, respectively (odds ratio 3.9 (95% CI, 2.7-5.9), p  < 0.001)., Conclusion: Implementation of circle priming has significantly increased the percentage of interoperability compliance for intravenous chemotherapy medications in our pediatric hematology/oncology patient care areas., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is limited information describing pharmacist participation in prophylactic enoxaparin monitoring in the surgical intensive care unit (SICU). Objective: Our study sought to: 1) characterize pharmacist recommendations for enoxaparin monitoring in trauma patients admitted to the SICU, 2) describe the frequency that medical providers accept pharmacist recommendations for enoxaparin monitoring in trauma patients admitted to the SICU, and 3) illustrate the frequency that trauma patients admitted to our SICU service achieve anti-factor Xa trough concentrations (AFXa-TRs) of 0.11 - 0.20 IU/mL following pharmacist recommendation to adjust prophylactic enoxaparin dosing. Methods: Adult patients who had an AFXa-TR drawn after at least three consecutive prophylactic enoxaparin doses between June 1, 2017 and March 1, 2018 were identified through chart review and included in this study. Patients were excluded based on the following criteria: 1) age less than 18 years, 2) anti-factor Xa (AFXa) level not representative of a trough concentration, 3) AFXa-TR not representative of steady state concentration, and 4) non-trauma based prophylactic enoxaparin dosing. This study was exempt from IRB review. Results: The final analysis consisted of 42 patients. A pharmacist provided at least one recommendation in 97.6% (41/42) of trauma patients with enoxaparin monitoring during their SICU stay. In total, a pharmacist made 170 recommendations, mean of 4.2 (SD 1.8) recommendations per patient. Recommendations were: 1) obtain an AFXa-TR, n=90; 2) adjust enoxaparin dose based on AFXa-TR, n=58; and 3) maintain enoxaparin dose based on AFXa-TR, n=22. Medical providers accepted 89.4% (152/170) of pharmacist recommendations for enoxaparin monitoring. Dose adjustments were made in 33 patients following pharmacist recommendation; of these, 27 had a repeat AFXa-TR following at least one dose adjustment. Target AFXa-TRs were achieved in 19/27 patients, indicating 70.4% had recommended AFXa concentrations. Conclusions: Pharmacists provided recommendations for prophylactic enoxaparin monitoring and dose adjustment in trauma patients admitted to the SICU. Medical providers regularly accepted pharmacist recommendations and trauma patients commonly achieved target AFXa-TR following pharmacist recommendation for dose adjustment. Further research is required to identify the optimal enoxaparin dose for VTE prophylaxis in trauma patients.

What Is Known and Objective: Current vancomycin monitoring guidelines recommend the use of area under the concentration-time curve (AUC 24 ) monitoring in patients with serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections by utilizing either a Bayesian approach or first-order analytic equations. Several open-access websites exist that allow estimation of vancomycin AUC 24 with the use of a single steady-state concentration. It is uncertain how these open-access calculators perform against guideline-recommended methods. The objective was to compare AUC 24 estimates from two online, open-access, single-concentration vancomycin calculators compared with the two-point pharmacokinetic (2PK) method., Methods: AUC 24 estimates were made using the 2PK reference method and the single-concentration vancomycin calculators, ClinCalc and VancoPK. The AUC 24 estimates from the 2PK reference method were compared to the online calculators by assessing bias (median AUC 24 difference) and precision (AUC 24 difference ± 100 mg*h/L). Clinical precision was also assessed by characterizing the frequency that the 2PK reference method and the online calculators showed clinical disagreement based on the following AUC 24 categories: (1) AUC 24  < 400 mg*h/L; (2) AUC 24 400-600 mg*h/L and (3) AUC 24  > 600 mg*h/L., Results and Discussion: A total of 253 patients were included in the study. The AUC 24 estimates from the ClinCalc and VancoPK single-concentration vancomycin calculators showed some bias and imprecision, though VancoPK appeared to have less. Clinical disagreement versus the 2PK reference method occurred in 31.2% and 19.4% of AUC 24 estimates from the ClinCalc and VancoPK single-concentration vancomycin calculators, suggesting clinical imprecision., What Is New and Conclusion: The AUC 24 estimates from single-concentration, online vancomycin calculators showed some bias and imprecision in comparison to the 2PK method. Institutions should validate these online, trough-only calculators relative to a 2PK method in their patient populations prior to adoption as standard-of-care., (© 2022 John Wiley & Sons Ltd.)

Background: The risk of linezolid-associated serotonin toxicity remains unclear. This study sought to evaluate the incidence of serotonin toxicity among hospitalized patients who received linezolid with or without concurrent serotonergic agents (SAs). Secondary outcomes were to assess the dose, agent selection and number of SAs., Methods: A single-centre, retrospective cohort study of hospitalized patients aged ≥18 years who received at least one dose of linezolid with or without SAs between 1 January 2014 and 30 June 2021 was performed. Patients were excluded if they were aged <18 years, had linezolid ordered but not administered, were pregnant or were incarcerated. Up to five concurrent SAs were assessed, and dose category was classed as low, moderate or high (dose <33%, 33-66% or >66% of maximum daily dose, respectively). Serotonin toxicity was identified by searching patients' electronic medical records. If identified, the Sternbach criteria and Hunter criteria were applied., Results: Of 2022 patients screened, 1743 were included in this study. Mean age, weight and linezolid duration were 58.5 years, 90.7 kg and 3.8 days, respectively. Approximately 67% (1168/1743) of patients received linezolid with at least one SA, and several patients received multiple SAs. Most patients (53.8%; 616/1144) received moderate- and/or high-dose SAs. Only two patients (0.11%) were identified as possible cases of serotonin toxicity based on the electronic medical record search. However, the incidence of serotonin toxicity was 0.06% (1/1743) based on the Sternbach criteria and 0% (0/1743) based on the Hunter criteria., Conclusions: Serotonin toxicity among hospitalized patients who received linezolid with or without SAs was exceedingly rare, even among those who received multiple and high-dose SAs., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited., Objective: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs., Methods: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel., Results: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%., Conclusions: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Background: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described., Objective: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use., Methods: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale., Results: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use., Conclusion and Relevance: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

Background: Compliance with guideline recommendations for surgical antibiotic prophylaxis (SAP) in colorectal surgery, particularly redosing, has been suboptimal at many institutions including ours. This study aimed to evaluate if single-dose antibiotic prophylaxis with ertapenem improves compliance with guideline recommendations for SAP versus multiple-dose antibiotic prophylaxis in elective colorectal surgery. Methods: A retrospective, cohort study of the use of ertapenem compared with standard of care antibiotic agents was performed in adult patients undergoing elective colorectal surgery at an academic medical center between January 2020 and February 2022. The primary outcome was compliance with guideline-recommended SAP for colorectal surgery. The secondary outcome was surgical site infections (SSIs) within 30 days after surgery. Results: A total of 135 patients were included in this study. Fifty-eight patients received single-dose antibiotic prophylaxis with ertapenem and 77 patients received multiple-dose antibiotic prophylaxis. Cefazolin plus metronidazole was the most common multiple-dose regimen (65 of 77). Single-dose antibiotic prophylaxis with ertapenem increased overall SAP compliance (96.6% vs. 64.9%; p < 0.001) as well as compliance with antibiotic administration within the recommended time period before incision (96.6% vs. 84.4%; p = 0.022), compliance with intra-operative antibiotic redosing when warranted (100% vs. 83.1%; p < 0.001), and compliance with guideline-recommended dosing (100% vs. 92.2%; p = 0.037). Surgical site infection rates were not statistically different between the groups (12.1% vs. 19.4%; p = 0.248). Conclusions: Single-dose antibiotic prophylaxis with ertapenem increased compliance with guideline-recommended SAP for elective colorectal surgeries. No statistically significant difference was observed in SSI rates regardless of the antibiotic regimen used.

Background: Trauma patients are at increased risk of developing venous thromboembolism given alterations in the coagulation cascade. Chemoprophylaxis with standard dosing of enoxaparin 30 mg subcutaneously twice daily has evolved to incorporate the use of anti-factor Xa (AFXa) trough level monitoring given concerns for decreased enoxaparin bioavailability in this patient population. Current available evidence suggests low rates of goal AFXa trough level achievement with standard enoxaparin dosing. Our study aims to identify the incidence of critically ill trauma patients that did not achieve goal AFXa trough levels and attempts to identify predictors that may influence the lack of achievement of goal levels. Methods: This was a retrospective, cohort analysis performed at a single academic medical center. Adult patients 18 years or older admitted to the surgical intensive care unit secondary to trauma who were initiated on standard prophylactic enoxaparin and had at least 1 AFXa trough level representative of steady state were included. Patient demographics and clinical data were collected, and descriptive statistics were utilized. All statistical tests were 2-tailed and a P  < .05 was considered significant. Variables with a P  < .10 on univariable analysis were included in a multivariable logistic regression analysis. Results: A majority of our patient population did not achieve goal AFXa trough levels while receiving standard doses of prophylactic enoxaparin (82.4% [108/131]). Sub-target AFXa levels were associated with higher creatinine clearance values. Positive predictors of obtaining target AFXa levels included automobile versus pedestrian mechanism of injury and requiring an enoxaparin dose escalation to at least 40 mg twice daily. Conclusions: Our study found low rates of achievement of goal AFXa trough levels in critically ill trauma patients receiving standard prophylactic enoxaparin dosing. Certain variables were identified as negative and positive predictors for achievement of goal AFXa trough levels, although the biologic plausibility of these predictors is questionable and requires further investigation., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting, and limited data describe AS interventions at hospital discharge. Acknowledging the potential value of discharge AS, we used our existing resources to review discharge oral antimicrobial prescriptions., Objective: The primary objective of this retrospective, single-center study was to evaluate the impact of an AS program on discharge oral antimicrobial prescriptions., Methods: Discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious diseases (ID) pharmacist, and recorded into our data collection tool from September 1, 2020, to February 28, 2021, were evaluated retrospectively. The primary outcome was to identify the frequency a drug-related problem (DRP) was identified by an ID pharmacist. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted., Results: Of the 803 discharge oral antimicrobial prescriptions reviewed, at least 1 DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. At least 1 intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). The most common types of interventions included recommendations for a different duration, a different dose or frequency, and antimicrobial discontinuation. When interventions to reduce treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5-10) days to 4 (0-5.5) days ( P < 0.001)., Conclusion and Relevance: An ID pharmacist's review of discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.

Purpose: While some guidelines recognize the need for β-lactam therapeutic drug monitoring (TDM), there is still a paucity of data regarding the prevalence of and barriers to performing β-lactam TDM in the United States. We sought to estimate the prevalence of β-lactam TDM, describe monitoring practices, and identify actual and perceived barriers to implementation among health systems in the US., Methods: A multicenter, cross-sectional, 40-item electronic survey was distributed to all postgraduate year 2 (PGY2) infectious diseases (ID) pharmacy residency program directors (RPDs) listed in the American Society of Health-System Pharmacists pharmacy residency directory. The primary outcome was the percentage of institutions with established β-lactam TDM. Secondary outcomes included assessing β-lactam TDM methods and identifying potential barriers to implementation., Results: The survey was distributed to 126 PGY2 ID RPDs, with a response rate of 31.7% (40 of 126). Only 8% of respondents (3 of 39) performed β-lactam TDM. Patient populations, therapeutic targets, and frequency and timing of obtaining repeat β-lactam concentration measurements varied among institutions. The greatest barrier to implementation was lack of access to testing with a rapid turnaround time. Institutions were unlikely to implement β-lactam TDM within the next year but were significantly more inclined to do so within 5 years (P < 0.001)., Conclusion: β-lactam TDM was infrequently performed at the surveyed US health systems. Lack of access to serum concentration testing with rapid turnaround and lack of US-specific guidelines appear to be considerable barriers to implementing β-lactam TDM. Among institutions that have implemented β-lactam TDM, there is considerable variation in monitoring approaches., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban., Objective: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban., Methods: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration., Results: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159)., Conclusion and Relevance: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed., Competing Interests: Declaration of Competing Interest The authors' have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Stroke is one of the leading causes of disability in the United States. Prompt secondary prevention decreases the risk for recurrence. Pharmacists have taken a more active role in poststroke care and are initiating prompt follow-up after hospital discharge. There are, however, limited descriptions providing insight on how to implement programs that address this need. The purpose of this article is to provide insights into the development of a pharmacist-driven transitions of care program for patients with stroke., Methods: This study was a single-center, retrospective assessment of patients contacted by a pharmacist. All data were analyzed descriptively. Our initial evaluation of the Pharmacists Act on Care Transitions in Stroke (PACT-Stroke) service was to quantify and categorize drug-related problems (DRPs), which included drug selection, drug form, dose selection, treatment duration, dispensing, drug use process, patient-related problems, and other. Patients were included if they were adults who experienced an ischemic stroke. Exclusion criteria for this service included pediatric patients, patients with hemorrhagic strokes, patients with transient ischemic attacks, patients >89 years of age, pregnant patients, and patients discharged to a rehabilitation facility immediately after stroke., Findings: A total of 27 patients were included in this analysis, with a total of 30 DRPs identified. After pharmacist intervention, roughly 83% of these DRPs were resolved., Implications: Implementing secondary prevention measures for patients with stroke is crucial. A pharmacist-led transitions of care pilot program was implemented to address this high-risk patient population. This article serves as a framework for implementation at other institutions that aim to provide similar services and can potentially be applied to other high-risk groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Thrombocytopenia can occur when using an Impella percutaneous ventricular assist device (pVAD), and heparin-induced thrombocytopenia (HIT) is often suspected. Data on heparin- and anticoagulant-free purge solutions in these devices are limited. Previous case reports have described argatroban-based purge solutions, both with and without systemic argatroban, at varying concentrations in patients with known or suspected HIT., Summary: A 33-year-old male was transferred to our institution and emergently initiated on life support with venoarterial extracorporeal membrane oxygenation (ECMO), an Impella pVAD, and continuous venovenous hemofiltration to receive an urgent aortic valve replacement. Over the next several days, the patient's platelet count declined with a nadir of 17 × 103/μL on hospital day 13. The patient's 4T score for probability of HIT was calculated as 4. All heparin products were discontinued on hospital day 15, and the patient was initiated on systemic infusion with argatroban 1,000 μg/mL at a rate of 0.2 μg/kg/min with a purge solution of argatroban 0.05 mg/mL. The systemic infusion remained at a rate of 0.2 μg/kg/min, and the total argatroban dose was, on average, less than 0.25 μg/kg/min. On hospital day 21, the patient was transferred to another institution., Conclusion: Systemic infusion and a purge solution with argatroban were used in a patient with an Impella pVAD with multisystem organ dysfunction and suspected HIT. The patient achieved therapeutic activated partial thromboplastin times without adjustment of the systemic argatroban infusion and did not experience bleeding or thrombosis. Further studies concerning the safety and effectiveness of argatroban-based purge solutions in patients with pVADs are needed., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking., Objective: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer., Methods: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m 2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events., Results: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group ( P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups., Conclusion: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

Purpose: To evaluate the chemical and physical stability of an admixture containing cefepime and vancomycin in a single volume of lactated Ringer solution at refrigerated temperatures. Methods: Cefepime 2000 mg and vancomycin 1000 mg were, respectively, reconstituted with 10 and 20 mL of sterile water for injection (SWFI) per manufacturer instructions. This resulted in cefepime and vancomycin concentrations of 200 and 50 mg/mL, respectively. The resulting cefepime and vancomycin solutions at 10 and 20 mL, respectively, were drawn up and injected into 1000 mL lactated Ringer solution. Aliquot samples were obtained on days 0 to 9, visually inspected for gross incompatibility, and then stored at -80°C. Samples were thawed on the day of the analysis and run through ultraperformance liquid chromatography. Area under the concentration-time curve (AUC) on each day was compared with baseline AUC values. Chemical stability was defined as an AUC more than 93% of the baseline value. Results: No evidence of gross physical incompatibility was observed by visual inspection. Cefepime and vancomycin replicants were more than 94.5% and 98% of baseline AUC values. Therefore, all sample replicants were found to be more than 93% of their baseline AUC value. Conclusion: An admixture containing cefepime 2000 mg and vancomycin 1000 mg in 1000 mL lactated Ringer solution appears to be chemically and physically stable at refrigerated temperatures for up to 9 days., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Disclaimer: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Alvimopan is a peripherally acting opioid receptor antagonist indicated to accelerate gastrointestinal (GI) recovery following surgery, but its benefits past GI recovery are unknown and evidence suggests that it may increase risk for myocardial infarction. The purpose of this study was to evaluate the efficacy of a pilot alvimopan stewardship program aimed at intervening to discontinue alvimopan use following GI recovery., Methods: This was a retrospective, observational study examining the first 5 months of the alvimopan stewardship pilot program. During this initial period, a pharmacy resident assessed whether each patient met criteria for GI recovery, defined as solid food toleration and first bowel movement or flatus. If a patient met the criteria for GI recovery, the resident intervened and recommended that the primary team discontinue alvimopan. Primary outcomes were the percentage of patients with alvimopan continued past GI recovery and the percentage of patients for whom alvimopan ordered past GI recovery was discontinued following intervention by stewardship. Secondary outcomes included the percentage of accepted recommendations to discontinue alvimopan following GI recovery and the number of alvimopan doses ordered following GI recovery., Results: In total, 73 patients were included in the study analysis, all of whom underwent abdominal and/or urologic surgery. Alvimopan was ordered to be administered in 35.6% (26/73) of patients after GI recovery. The stewardship program intervened and recommended discontinuation on 50% (13/26) of the alvimopan doses ordered past GI recovery. Recommendations were accepted by the primary team for 92.3% (12/13) of the patients. A total of 51 doses of alvimopan were ordered for administration past GI recovery, with an average of 2 doses per patient., Conclusion: A pilot pharmacy-driven alvimopan stewardship program was able to identify and intervene on alvimopan orders continued past GI recovery. Interventions decreasing alvimopan use past GI recovery could be of benefit by minimizing potential risk and decreasing potential costs without a negative impact on patient outcomes., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We describe the structure, implementation, and initial evaluation of a formal residency research certificate program (RRCP) designed to further advance residents' knowledge and skills in research in an effort to better prepare residents for research involvement during their careers., Summary: Pharmacy residency programs vary in the degree of emphasis on research education and training and the structure of resident research activities. Limited data describing formal research education and training for pharmacy residents are available. To better educate and prepare residents in the research process, State University of New York Upstate University Hospital developed and implemented a formal RRCP designed to educate and train residents in essential areas of the research process. Research seminars are delivered by preceptors with experience and training in research throughout the academic year to align with residency project tasks. Residents are also required to complete at least 1 residency project and submit a manuscript suitable for publication in a peer-reviewed journal. Upon successful completion of the program and project requirements, residents earn a certificate of completion. Initial data collected through formal resident assessments before and after RRCP completion demonstrated significant improvement in research knowledge (from an average score of 61.3% out of 100% to an average score of 84.7%, P = 0.002)., Conclusion: Post-RRCP assessment showed improvements in residents' confidence in several areas of research, including but not limited to research project design, ethical and regulatory principles of research, data collection, selection of appropriate statistical tests, manuscript writing, and the publication process. Residents strongly agreed that the RRCP improved their overall knowledge and perceptions of research., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: It is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)-based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC-based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC- or trough-based monitoring., Design: This was a single-center, retrospective cohort study., Setting and Participants: This study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC-based monitoring at our institution., Outcome Measures: The primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay., Results: A total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07-$601.05) for the AUC:MIC-based group compared with $316.79 ($253.36-$520.96) for the trough-based group (P = 0.687)., Conclusion: Vancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C-I) or intermittent infusion (I-I) vancomycin in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics., Design: Single-center propensity score-matched retrospective cohort study., Setting: OPAT clinic affiliated with two nearby hospitals., Patients: We identified 300 patients who received C-I or I-I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups., Measurements and Main Results: After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22-fold decrease in nephrotoxicity risk (C-I 6.8% [5/74 patients] vs I-I 18.9% [14/74 patients]; odds ratio 3.22, 95% confidence interval 1.10-9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I-I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C-I and I-I groups (13.5% [10/74 patients] vs 23.0% [17/74 patients], p=0.147)., Conclusion: In an OPAT setting, C-I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I-I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C-I versus I-I vancomycin., (© 2020 Pharmacotherapy Publications, Inc.)

OBJECTIVE: To test the common hypothesis that pharmacists may use more caution and resources when processing pediatric versus geriatric medication orders in the hospital setting.
DESIGN: A 26-item electronic survey was distributed to a sample of participating academic medical-center pharmacy directors with the request to disseminate it to staff pharmacists. The survey was resent at two-week intervals on two occasions.
MAIN OUTCOME MEASURE(S): To identify if pharmacists take more caution when processing geriatric or pediatric medication orders, to characterize the frequency pharmacists use drug information resources when processing these orders, and to assess the level of importance pharmacists place on guidelines for medication error prevention when processing medication orders.
RESULTS: A total of 173 out of 271 pharmacists completed the survey, resulting in a high final completion rate of 63.8%. Most were clinical, residencytrained pharmacists. A majority of respondents stated that they take more caution when verifying pediatric medication orders than they do for orders for older people (125 out of 172, or 72.7%). Pharmacists report they were 4.2 times more likely to refer to a drug information resource for ≥ 50% of pediatric orders versus geriatric orders (pediatric: 118 out of 171, or 69.0% vs. geriatric: 59 out of 172, or 34.3%; P < 0.001, or 95% confidence interval [CI] 4.156 [2.647-6.524]). Finally, pharmacists familiar with the guidelines for medication error prevention were 2.3 times more likely to state the pediatric guidelines were very important (pediatric: 51/171, or 29.8% vs. geriatric: 27/172, or 15.7%; P = 0.002, or 95% CI 2.28 [1.35-3.86]).
CONCLUSION: This survey reveals evidence for attitudinal differences in work practices for pharmacists working with medication orders relating to different age groups. Given the challenges involved in drug treatment for the older patient population, a similar level of caution, preparedness to refer to drug information, and to use guidelines should apply for both pediatric medication orders and those for older people, in order to provide safe and comprehensive care.

Purpose: After a sentinel event related to long-acting (LA) opioid administration at our institution and subsequent root cause analysis, an inpatient LA opioid restriction policy was implemented to improve patient safety. The objectives of this study were to evaluate the effect of an inpatient LA opioid restriction policy on inpatient therapy utilization and to compare rates of naloxone reversal events among patients administered LA opioids before and after policy implementation. Methods: To evaluate the first objective, an electronic medical record report was created to capture all inpatient LA opioid orders prescribed to adults at our institution between March 1, 2014, and July 30, 2017. Utilization was compared before and after policy implementation and use controlled for by patient days. To evaluate the second objective, naloxone administrations were identified via a query of the medical record between March 1, 2014, and July 30, 2017. Naloxone reversal events were independently evaluated by 2 trained reviewers, and a third when discrepancies existed. Rates of naloxone reversal events related to LA opioid administration were compared between the pre- and post-policy phase. Results: The results of our first objective demonstrate that policy implementation was associated with a statistically significant reduction in LA opioid utilization that was sustained throughout the study duration. For our second objective, among the 144 patients deemed to have an opioid-related naloxone reversal event, a LA opioid was administered to 12 patients (18.9%) in the pre-policy phase and 17 patients (15.9%) in the post-policy phase. This difference was not statistically significant (odds ratio [OR] = 1.629, confidence interval [CI] = 0.711-3.732, P = .248). Conclusion: A LA opioid restriction policy significantly reduced LA opioid utilization at our institution. Despite this, we did not find a significant reduction in inpatient naloxone reversals related to LA opioids. Further study is warranted to identify an optimal method to reduce LA opioid-related toxicity., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2018.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution., Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L., Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107)., Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Purpose: The purpose of this study was to (1) determine whether academic medical centers implemented area under the concentration-time curve (AUC)-based monitoring for vancomycin and (2) characterize perceived barriers to implementation and challenges experienced during the implementation process., Methods: A multicenter, cross-sectional electronic survey was distributed to pharmacy representatives from 124 academic medical centers within the Vizient University Health System Consortium Pharmacy Network., Results: Seventy-eight institutions completed the survey, representing a 62.9% response rate. Most institutions were approximately 500-1,000 beds (68/78, 87.2%), and pharmacists were primarily responsible for vancomycin therapeutic drug monitoring (66/78, 84.6%) using pharmacist-driven protocols (57/78, 73.1%). Less than one fourth (18/78, 23.1%) of responding academic medical centers performed AUC-based vancomycin monitoring, and the majority (12/18, 66.7%) used 2-point pharmacokinetics, with a smaller fraction using either Bayesian software or population-based pharmacokinetics. Of the responding institutions that only perform trough-based therapeutic drug monitoring (60/78, 76.9%), most (53/60, 88.3%) did not plan to or were unsure about transitioning to AUC-based monitoring within the next year. Both the most common challenge encountered (13/18, 72.2%) for institutions performing AUC-based monitoring and the most common barrier (44/60, 73.3%) to implementation of this monitoring strategy were pharmacist and/or provider unfamiliarity., Conclusion: The majority of surveyed academic medical centers have not yet implemented AUC-based vancomycin monitoring, and most institutions did not plan to adopt or were unsure about adopting this monitoring strategy within the next year., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The United States has seen an increased consumption of carbapenem antibiotics in recent years. The increased utilization of these agents has potential negative consequences, including the increasing incidence of carbapenem-resistant Enterobacteriaceae. Reasons for the rise in carbapenem use among providers in acute care hospitals are not well elucidated in literature. The objectives of this study were to identify factors that influence empiric carbapenem use among providers in a single academic medical center, and to assess therapeutic knowledge pertaining to carbapenem use. Methods: A cross-sectional, single-center, 9-item electronic research survey was developed independently and validated by an infectious diseases pharmacist and infectious diseases physician. The survey was distributed to email accounts of providers at a single academic medical center. Demographic data, factors affecting carbapenem prescription, and baseline therapeutic knowledge were assessed. Results: Ninety-five of 416 providers responded to the survey (response rate of 22.8%). Respondents were well distributed across all levels of training with primary roles in internal medicine and surgery. The most important factors influencing empiric carbapenem use were suspected pathogens at the site of infection, drug allergies, history of multidrug resistant organisms, severity of illness, type of infection, and local resistance rates. A recommendation from a pharmacist was selected as the most likely factor for deterring carbapenem use. Misconceptions pertaining to penicillin drug allergy and beta-lactam cross reactivity, knowledge of local resistance rates according to the institutional antibiogram, and comparative efficacy data for carbapenems were apparent across all levels of training. Conclusions: Provider misconceptions regarding several factors appear to contribute to unnecessary use of carbapenems. An opportunity exists for hospital pharmacists to improve the prescribing patterns of carbapenems by correcting provider misconceptions through education., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Limited evidence exists evaluating pharmacokinetic thresholds for vancomycin efficacy and nephrotoxicity using non-Bayesian methods. The objective of this study was to evaluate the 24-h steady-state vancomycin area under the concentration-time curve (AUC 24 ) thresholds for efficacy and nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSA-B) after implementing two-point pharmacokinetic therapeutic drug monitoring. A single-centre, retrospective cohort study was performed including adult patients admitted between 1 June 2016 and 1 January 2018 with MRSA-B treated with vancomycin for ≥72 h. The AUC 24 was calculated using peak and trough vancomycin serum concentrations. Clinical success was defined as defervescence and blood culture sterilisation by Day 7. Nephrotoxicity was defined as an increase in serum creatinine of >0.5 mg/dL (or ≥50%) from baseline. Classification and regression tree (CART) analyses were performed to identify AUC 24 thresholds for efficacy and nephrotoxicity. Forty-six patients were included in the study. Clinical success and nephrotoxicity were observed in 81.8% and 13.0%, respectively. The CART-derived vancomycin AUC 24 thresholds for clinical success and nephrotoxicity were ≥297 mg·h/L and ≥710 mg·h/L, respectively. Patients with an AUC 24 ≥297 mg·h/L had a >2.7-fold increase in clinical success compared with those who did not (89.5% vs. 33.3%, respectively; P = 0.01), and patients with an AUC 24 ≥710 mg·h/L had a >7-fold increase in nephrotoxicity compared with those with an AUC 24 <710 mg·h/L (66.7% vs. 9.3%, respectively; P = 0.04). This study supports current recommendations to target vancomycin AUC 24 values of 400-600 mg·h/L when calculated using two-point pharmacokinetics, although a wider range may exist., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: Strategies that reduce the time to antimicrobial administration, such as the availability of premix antimicrobials (PMAs) in the emergency department (ED), may better align with the goals of the Surviving Sepsis Campaign and improve outcomes in septic patients. The objective of this study was to evaluate the impact of antimicrobial preparation on time to administration in septic patients located in the emergency department (ED)., Methods: This was a retrospective, single-center, cohort study and adult patients with a diagnosis of sepsis who received at least one initial intravenous (IV) antimicrobial in the ED were included. Time to complete an empiric antimicrobial therapy was defined as the time between prescriber order entry and the infusion initiation time of the final antimicrobial agent of a patient's antimicrobial regimen. Appropriate, empiric antimicrobial therapy was based on treatment recommendations by nationally accepted guidelines for the specific indication., Results: The first antimicrobial was initiated earlier when available as a PMA preparation (median (IQR): premix 25 minutes (16.5-42.3) vs. non-premix 46 minutes (20-102), p=0.027). When comparing complete, empiric antimicrobial regimen administration, there was no difference in time to administration between regimens containing one or more non-premix antimicrobials and regimens containing all PMAs (median (IQR): premix 69 minutes (21-115) vs. non-premix 65 minutes (38.5-133.8); p=0.455)., Conclusions: PMA preparations significantly reduced time to administration of the first antimicrobial agent for septic patients treated in the ED, but time to administration of subsequent antimicrobials were not improved.

Background: Severe sepsis and septic shock represent common presentations in the emergency department (ED) and have high rates of mortality. Guideline-recommended goals of care have been shown to benefit these patients, but can be difficult to provide., Objective: To determine whether the use of a premixed bag consisting of 2 g cefepime and 1 g vancomycin in 1000 mL of normal saline increases the probability of patients receiving Surviving Sepsis Campaign (SSC) recommendations for the initiation of antimicrobials and fluid challenge., Methods: This was a 6-month retrospective analysis conducted to determine the impact of an intervention on time to antimicrobials and fluid administration in patients with severe sepsis and septic shock. Patients presenting to the ED who received a diagnosis of severe sepsis or septic shock and were administered 2 antibiotics were eligible for inclusion. The primary outcome assessed was compliance with SSC recommendations for antibiotic and fluid goals within 3 hours of ED arrival., Results: A total of 160 patients were included. In the intervention group, 63.8% of patients met the primary outcome compared with 22.5% in the historical group (odds ratio = 2.32; 95% CI = 1.67-3.23). Time to administration of antibiotics was less with the combination antibiotic bag (CAB: median (IQR) = 72 (48-115) minutes; non-CAB: median (IQR) = 135 (102-244) minutes; P ≤ 0.001)., Conclusion: This intervention significantly increased the proportion of patients provided with SSC goals of care. Such interventions have not been reported previously and could be meaningful in the management of severe sepsis and septic shock.

Background: Despite the numerous benefits of outpatient parenteral antimicrobial therapy (OPAT), appreciable risks of drug-related problems (DRPs) exist. No studies to date comprehensively assess DRPs in this population., Objectives: Objectives of this study were to (1) characterize the frequency and types of DRPs experienced by patients discharged on OPAT and (2) determine the fraction of adverse drug reactions (ADRs) resulting in hospital readmission or emergency department (ED) presentation and changes in therapy., Methods: This was a retrospective chart analysis evaluating consecutive adult patients discharged on OPAT between May 2015 and October 2015. Patients were assessed for the presence of DRPs until the cessation of antimicrobial treatment, including oral step-down therapy. The outcome of each ADR was recorded, including those resulting in hospital readmissions, presentation to the ED, or changes in antimicrobials., Results: Among 144 patients discharged on OPAT, 199 DRPs occurred in 91 (63.2%) patients. Harm and potential impaired efficacy occurred in 76.9% and 23.1%, respectively. The ADRs comprised 59% of DRPs, occurring in 44.4% of patients. The second most common DRP type was drug interactions (DIs), accounting for 22.6% of DRPs. Rifampin, fluoroquinolones, and daptomycin had the highest frequencies of preventable DRPs in the form of DIs, whereas cephalosporins had the fewest DRPs. Approximately 26% of ADRs caused changes in therapy and 9% resulted in hospital readmission or ED utilization., Conclusion: DRPs with the potential to cause patient harm or impair treatment efficacy often occur with OPAT, most commonly ADRs and DIs. Enhanced monitoring and transitions of care management may reduce the incidence of these DRPs.

Purpose: To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400., Methods: A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: <10, 10 to 14.9, and >20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment., Results: Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs <10 mg/L were 73% less likely to attain an AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P < .001)., Conclusion: Achieving vancomycin serum trough concentrations of 15 to 20 mg/L did not result in an increased attainment of the AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

Background: Anti-Xa monitoring is utilized to measure the extent of anticoagulation in certain patient populations receiving enoxaparin. It is essential to accurately obtain this pharmacodynamic marker for safe and effective anticoagulation management. Objectives: To determine the frequency of correctly drawn anti-Xa concentrations in accordance with predefined institutional criteria and to determine the number of dose adjustments implemented based on incorrectly drawn anti-Xa concentrations. Methods: This was a retrospective, single-center, cohort study among adult patients who received treatment doses of enoxaparin with measured anti-Xa concentrations. Patients were excluded if they were pregnant, on hemodialysis, or received prophylactic dosing. Anti-Xa levels were defined as correctly measured if they were drawn 3 to 5 hours after the dose during steady state concentrations. Descriptive statistics were performed and analyzed via SPSS software. Results: Overall, 203 patients were reviewed and 59 patients with 74 anti-Xa levels were included. The majority of anti-Xa levels (57/74; 77%) were drawn incorrectly and often resulted in collection of repeat anti-Xa samples. There were 12 documented dose adjustments and approximately 42% (5/12) were based on incorrectly drawn anti-Xa levels. Anti-Xa levels were within target range approximately 45% of the time. Conclusions: Enoxaparin anti-Xa concentrations are frequently drawn incorrectly and dose adjustments are often performed based on these unsupported anti-Xa levels. This may present a potential risk to compromise patient safety.

Background: Published literature has demonstrated commercially available premix vancomycin (5 mg/mL) and piperacillin-tazobactam (67.5 mg/mL) as physically compatible via simulated Y-site methodology. Compatibility via actual Y-site infusion has yet to be established. Objective: To assess and compare the compatibility of commercially available premix concentrations of vancomycin and piperacillin-tazobactam via simulated and actual Y-site evaluation. Methods: Vancomycin and piperacillin-tazobactam were tested using simulated and actual Y-site infusion methodologies. Simulated Y-site compatibility was performed using previously published methods via visual inspection, turbidity evaluation, and pH evaluation. Evaluation occurred immediately, 60 minutes, 120 minutes, and 240 minutes following mixing for each mixture and control. Mixtures were considered physically incompatible if there was visual evidence of precipitation or haze, an absorbance value was greater than 0.01 A, or an absolute change of 1.0 pH unit occurred. Actual Y-site infusion was simulated to mirror antibiotic infusion in the clinical setting by nursing personnel using smart pumps and intravenous tubing. Results: No evidence of physical incompatibility was observed during simulated Y-site testing via visual inspection, turbidity assessment, and pH evaluation. Conversely, physical incompatibility was observed to the unaided eye within 2 minutes during actual Y-site infusion. Conclusions: Despite observed compatibility between vancomycin and piperacillin-tazobactam via simulated Y-site testing, visual evidence of physical incompatibility was observed during actual Y-site infusion. This poses a potential compromise to patient safety if these antibiotics are administered simultaneously in the clinical setting. Actual Y-site testing should be performed prior to clinical adoption of compatibility studies that are based solely on simulated methodologies.

Background & objective: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15–20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. Method: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. Results: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41–2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23–0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73–3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31–1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73–1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62–0.90), p = 0.002]. Conclusion: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. [ABSTRACT FROM AUTHOR]

Limited data exists on the safety and efficacy with the concomitant use of 4 factor prothrombic complex concentrate (4F-PCC) and andexanet alfa (AA). This case series describes 7 patients at our institution who received both 4F-PCC and AA for the management of life-threatening bleeding associated with apixaban or rivaroxaban. Four patients received AA due to worsening bleeding after 4F-PCC. Of the 7 patients in this case series, 1 had a documented thrombotic event which was an acute ischemic stroke. The thrombotic event rate in our case series was similar to the incidence of thrombotic events reported with the use of AA alone. In-hospital mortality occurred in 2 of 7 patients with 1 additional patient discharged to hospice care. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the impact of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) protocol on the vancomycin length of therapy (LOT) for skin and soft tissue infections (SSTIs). Design: Retrospective quasi-experimental pre- and post- MRSA nasal PCR protocol implementation study. Setting: Tertiary-care academic medical center in Jacksonville, Florida. Patients: Eligible patients received empiric vancomycin for SSTIs from January 1st to September 30th 2020 (pre-implementation group) and from January 1st to September 30th 2022 (post-implementation group). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with SSTIs. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary outcomes were incidence of acute kidney injury (AKI), number of vancomycin levels collected, and hospital length of stay (LOS). Results: The study included 131 patients (pre-implementation, n = 86 and post-implementation, n = 45). There was no significant difference in vancomycin length of therapy (LOT) between implementation groups: mean LOT in days and standard deviation (SD) were 2.7 (1.9) and 2.6 (1.3), respectively, p-value 0.493. Of significance, in the post-implementation group, vancomycin LOT between patients with a negative and positive MRSA PCR were 2.3 (1.1) and 3.9 (1.6), p-value 0.006. There was no difference in secondary outcomes. Conclusion: The utilization of the MRSA nasal PCR to guide vancomycin de-escalation did not significantly change the vancomycin LOT, however in the post-implementation group there was a significant difference in vancomycin LOT between negative and positive MRSA PCRs. [ABSTRACT FROM AUTHOR]

Background: Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity., Methods: A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Random-effects models were used to compare the differences in nephrotoxicity., Results: Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy., Conclusions: The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Background: Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM., Methods: This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks., Results: Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings., Conclusions: Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice., Competing Interests: M. H. Scheetz reports a previous research contract with Allecra. E. F. Barreto reports an ongoing consultancy agreement with Wolters-Kluwer. For the remaining authors, no conflicts of interest were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4–8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available. [ABSTRACT FROM AUTHOR]

Objective: Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who receive both andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC). The aim of this case series is to evaluate the safety and efficacy outcomes in patients receiving the two agents in combination. Methods: Electronic medical records of patients who received both 4F-PCC and andexanet alfa for nontraumatic intracranial hemorrhage from January 2019 to March 2022 were retrospectively reviewed. Hemostatic efficacy and complications related to concurrent use of 4F-PCC with andexanet alfa were documented. Results: Nine patients received 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated intracranial bleeding, eight of whom required reversal of apixaban. Of these nine patients, five patients died within 28 days for a 56% incidence of mortality. The average time from 4F-PCC administration to andexanet alfa administration was 3 hours and 9 minutes. Most doses of andexanet alfa were given for concern for bleed expansion after 4F-PCC administration. Hemostatic efficacy based on stability of repeat computed tomography scans post-administration of both agents was found in six patients (66.67%), with a 55.56% n incidence of thromboembolism, including two pulmonary embolisms, two deep vein thromboses, and one renal artery thrombosis. Conclusion : Risks and benefits should be weighed to determine if there is benefit to adding andexanet alfa to 4F-PCC in patients with incomplete hemostasis and life-threatening hemorrhage. The combination of andexanet alfa and 4F-PCC may increase the risk of thrombotic complications without improving mortality. [ABSTRACT FROM AUTHOR]