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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%. [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]

Purpose: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. Methods: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. Results: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. Conclusion: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation. [ABSTRACT FROM AUTHOR]

Background: There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting for these variables. Methods: We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset. Results: Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively (P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively (P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively (P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67-6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant. Conclusion: Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds. [ABSTRACT FROM AUTHOR]

Background Bacterial infections such as osteomyelitis and endocarditis routinely require several weeks of treatment with intravenous (IV) antimicrobials. Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive IV antimicrobials in an outpatient clinic or at home. The outcomes and costs of such treatments remain uncertain. Methods We conducted a retrospective observational cohort study over a 5-year study interval (1 June 2012 to 31 March 2018) using population-based linked administrative data from British Columbia, Canada. Patients receiving OPAT following a hospitalization for bacterial infection were matched based on infection type and implied duration of IV antimicrobials to patients receiving inpatient parenteral antimicrobial therapy (IPAT). Cumulative adverse events and direct healthcare costs were estimated over a 90-day outcome interval. Results In a matched cohort of 1842 patients, adverse events occurred in 35.6% of OPAT patients and 39.0% of IPAT patients (adjusted odds ratio, 1.04 [95% confidence interval {CI},.83–1.30; P =.61). Relative to IPAT patients, OPAT patients were significantly more likely to experience hospital readmission (30.5% vs 23.0%) but significantly less likely to experience Clostridioides difficile diarrhea (1.2% vs 3.1%) or death (2.0% vs 8.8%). Estimated mean direct healthcare costs were $30 166 for OPAT patients and $50 038 for IPAT patients (cost ratio, 0.60; average cost savings with OPAT, $17 579 [95% CI, $14 131–$21 027]; P <.001). Conclusions Outpatient IV antimicrobial therapy is associated with a similar overall prevalence of adverse events and with substantial cost savings relative to patients remaining in hospital to complete IV antimicrobials. These findings should inform efforts to expand OPAT use. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Current vancomycin monitoring guidelines recommend the use of area under the concentration‐time curve (AUC24) 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 AUC24 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 AUC24 estimates from two online, open‐access, single‐concentration vancomycin calculators compared with the two‐point pharmacokinetic (2PK) method. Methods: AUC24 estimates were made using the 2PK reference method and the single‐concentration vancomycin calculators, ClinCalc and VancoPK. The AUC24 estimates from the 2PK reference method were compared to the online calculators by assessing bias (median AUC24 difference) and precision (AUC24 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 AUC24 categories: (1) AUC24 < 400 mg*h/L; (2) AUC24 400–600 mg*h/L and (3) AUC24 > 600 mg*h/L. Results and Discussion: A total of 253 patients were included in the study. The AUC24 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 AUC24 estimates from the ClinCalc and VancoPK single‐concentration vancomycin calculators, suggesting clinical imprecision. What Is New and Conclusion: The AUC24 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. [ABSTRACT FROM AUTHOR]

Introduction: The latest vancomycin therapeutic drug monitoring guidelines for serious MRSA infections have made a pivotal change in dosing, switching from targeting trough levels to AUC dosing. Because of these new recommendations, antimicrobial stewardship programs across the country are tasked with implementing AUC based dosing. Objectives: To assess plans for institutional adoption of vancomycin AUC dosing programs and perceptions of currently used programs in hospitals across the US. Methods: An electronic survey was distributed to members of the American College of Clinical Pharmacy IDprn Listserv and American Society of Health-System Pharmacists between May and June 2020 to assess current institutional vancomycin dosing. Institutional program use and multiple software user parameters were analyzed using descriptive statistics. Results: Two hundred two pharmacists responded to the survey with the majority practicing in institutions with 251-500 beds. Most respondents have yet to implement AUC dosing (142/202, 70.3%) with many of them planning to do so in the next year (81/142, 57.0%). Of those that already implemented AUC dosing programs, purchased Bayesian software (23/60, 38.3%) and homemade software (21/60, 35.0%) were the 2 methods most frequently utilized. Purchased Bayesian software users were more likely to recommend their software to other institutions and ranked user friendliness higher compared to non-purchased software. Conclusion: Most respondents have not made the switch to vancomycin AUC dosing, but there is a growing interest with many institutions looking to adopt a program within the next year. [ABSTRACT FROM AUTHOR]

Objective: The transition to area under the curve (AUC) vancomycin monitoring requires substantial updates in pharmacy policies and procedures. The study facility was tasked with transitioning from a consult-based collaborative agreement to an automatic pharmacist management policy on all intravenous (IV) vancomycin orders. The purpose of this quality assessment (QA) study was to evaluate the effectiveness of this transition. Methods: The primary outcome was the proportion of patients with pharmacist assessment of pharmacokinetics and dosing with documentation in IV vancomycin treated patients from January-June 2020. Secondary outcomes included the proportion of AUC24 levels within therapeutic range, the incidence of acute kidney injury (AKI) and treatment failures in patients treated ≥72 hours compared to a historical, trough-based cohort. Results: There were 88 patients in the QA analysis with 100% having a pharmacist assessment with documentation. There were 34 patients treated ≥72 hours in the AUC group, 36 in the trough-based group. AUC24 fell within desired range in 45% of monitored patients. Rates of AKI (9% vs 11%, p = 0.75) and treatment failures were similar (3% vs 0%, p = 0.3). Conclusion: The transition from consult-based to an automatic pharmacy management agreement was successful with similar safety and efficacy compared to a historical trough-based cohort. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Levetiracetam is an antiepileptic medication commonly used in critical care areas for seizure treatment or prophylaxis. Compatibility data of levetiracetam with other critical care medications are limited, which can make administration challenging. This study aims to assess the physical Y-site compatibility of intravenous levetiracetam with some other commonly used critical care medications. Methods: Y-site administration was simulated by independently mixing levetiracetam with each of 11 selected medications in a 4-dram, colorless, screw-cap, glass vial, at a 1:1 ratio. Clinically used concentrations of each medication were compounded in 0.9% sodium chloride following United States Pharmacopeia chapter 797 standards. Physical compatibility was observed and assessed at 0, 15, and 30 minutes after mixing. Medication mixtures were considered physically incompatible if there was visual evidence of color change, gas evolution, haze, or particulate formation, pH change > 10%, or if they had an absorbance value > 0.010 A. Results: No evidence of physical incompatibility was observed during simulated Y-site testing with cisatracurium 1 mg/mL, dexmedetomidine 4 µg/mL, fosphenytoin 15 mg PE/mL, norepinephrine 16 mg/mL, norepinephrine 32 mg/mL, norepinephrine 64 mg/mL, piperacillin-tazobactam 33.75 mg/mL, propofol 10 mg/mL, vancomycin 5 mg/mL, or vasopressin 1 unit/mL when tested in 0.9% sodium chloride. Levetiracetam was incompatible with piperacillin-tazobactam 45 mg/mL. Conclusion: Levetiracetam 5 mg/mL in 0.9% sodium chloride was found to be physically compatible for 30 minutes with 10 of the 11 medications tested during simulated Y-site administration. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious Staphylococcus aureus infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort. Pharmacist perception of the practice change is largely unknown and warrants investigation. Methods: An electronic survey was disseminated via e-mail to pharmacists 5 months post-AUC implementation. Items of interest were focused on pharmacist perception, including quantity of patients monitored using AUC, justification of the practice change, differences in efficacy and safety, and changes in monitoring time requirements. Results: The pharmacist survey was distributed to 196 pharmacists and 84 responded (43% response rate). Eighty-one pharmacists had monitored patients using AUC methods. Sixty-nine percent of these respondents perceived the change to result in increased or slightly increased patient safety, 27% described no difference, and 4% stated safety was decreased or slightly decreased. Forty-two percent perceived the transition to result in increased or slightly increased efficacy, while 48% noted no difference and 10% responded that efficacy was decreased or slightly decreased. Pharmacists stated the creation of an institutional calculator decreased the time required to calculate AUC. Conclusion: After the change to AUC monitoring, pharmacists perceived improvements in safety outcomes while efficacy was at least similar if not increased. [ABSTRACT FROM AUTHOR]

Background Vancomycin optimization is challenging, requiring careful therapeutic drug monitoring (TDM) to avoid toxicity and ensure an efficacious concentration. Most prescriptions are empiric and often discontinued within 72 hours, which makes early TDM unnecessary. Although TDM using trough levels is common, the area under the concentration–time curve (AUC) is the preferred pharmacodynamic target. We studied the effect of a pharmacy-driven vancomycin collaborative practice agreement (CPA) at a children's hospital that delayed TDM up to 72 hours and targeted a 2-point 24-hour AUC of ≥400 mg × h/L. Methods We retrospectively reviewed vancomycin courses in patients aged ≥30 days who received vancomycin between April 1, 2011, and August 30, 2017. We implemented the CPA on June 1, 2014. Outcomes included CPA use, use of TDM, dosage adjustments, and development of acute kidney injury; we compared courses given while monitoring only trough levels (TO-TDM) with those given while using the CPA (AUC-TDM). We performed interrupted time series analyses to account for preintervention trends. Results We included 2379 courses in the TO-TDM period and 2155 in the AUC-TDM period. During AUC-TDM, 87% of the courses were managed by the CPA. In adjusted interrupted time series analyses, CPA implementation was associated with an initial change in level of −0.265 (95% confidence interval [CI], −0.336 to −0.189) TDM and an initial change in level of −0.332 (95% CI, −0.506 to −0.163) dosage adjustments. The 1-year risk of acute kidney injury decreased after CPA implementation (odds ratio, 0.695 [95% CI, 0.539–0.91]). Conclusion The pharmacy-driven vancomycin CPA resulted in less monitoring and fewer dose adjustments without increasing AKI. [ABSTRACT FROM AUTHOR]

Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range. [ABSTRACT FROM AUTHOR]

Background. To better monitor patients on outpatient parenteral antimicrobial therapy (OPAT), we need an improved understanding of risk factors for and timing of OPAT-associated adverse drug events (ADEs). Methods. We analyzed a prospective cohort of patients on OPAT discharged from 2 academic medical centers. Patients underwent chart abstraction and a telephone survey. Multivariable analyses estimated adjusted incident rate ratios (aIRR) between clinical and demographic risk factors and clinician-determined clinically significant ADEs. Descriptive data were used to present patient-reported ADEs. Results. Of 339 patients enrolled in the study, 18.0% experienced an ADE (N = 65), of which 49 were significant (14.5%, 2.24/1000 home-OPAT days). Patients with longer courses of therapy had lower rates of ADEs compared with patients treated for 0-13 days (14-27 days: aIRR, 0.44; 95% confidence interval [CI], 0.20-0.99; at least 28 days: aIRR, 0.11; 95% CI, 0.056-0.21). Risk factors for ADEs included female gender and receipt of daptomycin or vancomycin, while treatment for uncomplicated bacteremia and empiric treatment were associated with lower rates of ADEs. Conclusions. OPAT-related ADEs were common and often occurred within 2 weeks of hospital discharge. Patients on OPAT should be monitored more closely for ADEs, including clinical assessment and laboratory monitoring, especially within the first weeks after hospital discharge and particularly among women and patients who receive vancomycin. [ABSTRACT FROM AUTHOR]