Accuracy of 4 Free Online Dosing Calculators in Predicting the Vancomycin Area Under the Concentration-Time Curve Calculated Using a 2-Point Pharmacokinetic Approach.

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.

Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis.

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.

Validation of Methicillin-Resistant Staphylococcus aureus (MRSA) Risk Factors in Predicting MRSA Community-Acquired Pneumonia at an Academic Medical Center.

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

Prophylactic Enoxaparin in Critically Ill Trauma Patients: Evaluation of the Initial Dose.

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.

Chemical and Physical Stability of an Admixture Containing Cefepime and Vancomycin in Lactated Ringer Solution.

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.

Effect of a Standardized Treatment Panel on Hypoglycemic Events in Hospitalized Acute Hyperkalemic Patients Treated With Intravenous Regular Insulin.

Purpose: Regular insulin is a commonly utilized treatment option for acute hyperkalemia. Despite its benefit, hypoglycemia and associated morbidity/mortality remain important concerns. This institution recently created a treatment panel to standardize regular insulin dosing (0.1 unit/kg) and blood glucose (BG) monitoring in patients with acute hyperkalemia. The purpose of this study is to investigate whether the order panel reduces hypoglycemic events in adults treated with intravenous (IV) regular insulin for hyperkalemia and to determine the effect the treatment panel has on regular insulin dosing, serum potassium, BG monitoring, and dextrose supplementation. Methods: This retrospective study was performed at a single academic medical center. Adults receiving IV regular insulin for acute hyperkalemia were included if BG was assessed prior to and following regular insulin administration. Primary outcome was hypoglycemia within 4 hours of regular insulin administration. Secondary outcomes were the change from baseline serum potassium, frequency of severe hypoglycemia, BG checks within 30 minutes prior to and within 4 hours following insulin administration, regular insulin dosing, and administration of dextrose 50% in water (D50W) following regular insulin administration. Hypoglycemia and severe hypoglycemia were defined as a BG concentration of <70 mg/dL and <50 mg/dL, respectively. Results: One hundred sixty-five patients were included; 75 using the treatment panel and 90 not. Patients using the treatment panel received a lower median (interquartile range [IQR]) regular insulin dose (.10 [0.09-0.10 unit/kg] vs 0.11 [0.09-0.14 unit/kg], P = .004) and had more frequent BG checks during the 4 hours following regular insulin administration (median [IQR]: 4 [3-5] vs 2 [1-3], P < .001). Hypoglycemia (13.3% vs 27.8%, P = .024) and severe hypoglycemia (2.7% vs 11.1%, P = .038) occurred less frequently with the treatment panel. Similar decreases in serum potassium were noted following IV regular insulin administration. Conclusions: Acute hyperkalemic patients utilizing a standardized treatment panel for the dosing and monitoring of IV regular insulin experienced fewer hypoglycemic and severe hypoglycemic episodes and had similar potassium lower effects. The treatment panel decreased regular insulin dosing and increased BG monitoring prior to and following regular insulin administration.

Evaluation of a Long-Acting Opioid Restriction Policy: Does Restriction Reduce the Need for Naloxone Reversal?

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.

Impact of a Combination Antibiotic Bag on Compliance With Surviving Sepsis Campaign Goals in Emergency Department Patients With Severe Sepsis and Septic Shock.

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.

Changes in Pharmacy Residency Training Design Between 2012 and 2017: A Perspective of Academic Medical Centers.

Purpose:The role of health-system pharmacists continues to expand, and this area of pharmacy practice increasingly requires augmented baseline training. It is unclear how Post Graduate Year 1 (PGY-1) pharmacy residencies may be changing to meet these needs.The objectives of our survey were to describe PGY-1 pharmacy residency program design among academic medical centers, characterize program changes enacted over 5-year period, and describe career paths among PGY-1 pharmacy residency graduates. Methods: A 32-item questionnaire was developed independently, which was reviewed and validated by 4 residency program directors. The survey was uploaded to an online survey tool and sent electronically to residency program directors of 109 Vizient academic medical centers with PGY-1 pharmacy residency programs. Residency program directors were identified from a list of Vizient-participating hospitals. The survey was re-sent at 2-week intervals on 4 occasions to improve response rates. SPSS version 23.0 was used to analyze the data. Results: Overall, 49 (45%) of hospitals responded to the survey. Survey responses showed statistically significant increases over the 5-year survey period in the following areas: the number of PGY-1 resident positions offered (P = .001), percent of time spent on teaching experiences (P = .001), and percentage of PGY-1 residents pursuing PGY-2 or fellowship training (P = .026). Conclusion: We found that PGY-1 pharmacy residency programs at Vizient academic medical centers have undergone limited changes over the 5-year survey period and substantial variation exists between program designs. The most common change to program design was an increase in the percentage of time residents spend on teaching experiences. There was an increase in residents pursuing PGY-2 or fellowship training, which may suggest a shift toward increased specialization in clinical pharmacy practice or may reflect changes in the availability of job opportunities.

Clinical Feasibility of Monitoring Enoxaparin Anti-Xa Concentrations: Are We Getting It Right?

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.

Evaluation of dabigatran utilization and risk among hospitalized patients.

BACKGROUND: Few data exist to evaluate the use of dabigatran among hospitalized patients and this population that may be at increased risk for toxicity or reduced efficacy. As such, the objectives of this study were to describe the characteristics of hospitalized patients prescribed dabigatran and to compare select characteristics with patients included in the Randomized Evaluation of Long-Term Anticoagulation (RE-LY) phase III clinical trial. METHODS: A cross-sectional study was performed at Upstate University Hospital. Select patient characteristics, including age, renal function, and drug interaction exposure, were compared with those for patients in the RE-LY trial. RESULTS: The study included 140 patients. Mean age was 69.7 years (SD = 13.8) and 72 (51.4%) were male. The mean CHADS2 score was 2.48 as compared with 2.2 in RE-LY. Significantly more patients in our study had moderate to severe renal dysfunction (creatinine clearance [CrCl] < 50 mL/min) as compared with the RE-LY trial (27.5% vs 19.4%, P = .0207) when analyzing our study patients' worst recorded CrCl. Among the 29 patients prescribed dose-adjusted dabigatran, 3 were correctly dose adjusted, 2 were overdosed, and 26 were underdosed. At least 1 pharmacokinetic drug interaction with dabigatran occurred in 110 study patients (78.6%). Use of proton pump inhibitors was more predominant in our study population when compared with RE-LY (64.3% vs 13.9%, P < .0001). CONCLUSIONS: Hospitalized patients exhibit multiple characteristics that place them at heightened risk for altered dabigatran drug concentrations and may have a heightened risk for clinical sequelae related to dabigatran use.

Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer.

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/m2 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.

Implementation of a formal pharmacy residency research certificate program.

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.