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.

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.

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.

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.

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.

A single-center cost analysis assessing a change in vasopressin formulation.

PURPOSE: Cost savings achieved at an academic medical center by reformulating the institution's standard vasopressin infusions to reduce waste are described. SUMMARY: After a retrospective review of vasopressin utilization over a 4-month period revealed that only approximately 40% of dispensed vasopressin units were actually administered to patients, pharmacy leaders determined that the institution's standard vasopressin concentration for continuous infusions (100 units in 100 mL of sodium chloride 0.9% injection) was resulting in substantial waste, as many infusion preparations were not needed within the 18- to 24-hour expiration window. A concentration of 20 units/100 mL was adopted as the new standard formulation for vasopressin continuous infusions, with use of alternative concentrations allowed on a restricted basis. A pre-post study to assess the impact of the formulation change indicated a 38.7% decrease in vasopressin utilization (from 21,900 to 8,480 units) relative to utilization in a retrospective sample of patients who received vasopressin infusions prior to the formulation change. This reduced utilization equated to a cost decrease of $55,656.20 (as calculated on the basis of 2017 cost estimates) or $77,214.23 (as calculated on the basis of 2019 cost estimates) for the time period collected. It was estimated that the new formulations could yield annual cost savings ranging from $222,625 to $308,857. CONCLUSION: To our knowledge, this is the first description of cost savings following a change in formulation of vasopressin for continuous infusions. Other institutions could consider employing a similar approach in addition to the previously reported cost-saving interventions, such as lower vasopressin starting doses and vasopressin restriction policies.

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.

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.

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.

Verifying Medication Orders in the Older Population: Are We Using Enough Caution?

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.

Nephrotoxicity Risk and Clinical Effectiveness of Continuous versus Intermittent Infusion Vancomycin Among Patients in an Outpatient Parenteral Antimicrobial Therapy Program.

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.

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.

Readiness to implement vancomycin monitoring based on area under the concentration-time curve: A cross-sectional survey of a national health consortium.

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.