Robert W. Seabury

Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

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.

Y-site Incompatibility between Premix Concentrations of Vancomycin and Piperacillin-Tazobactam: Do Current Compatibility Testing Methodologies Tell the Whole Story?:

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.

Characterization of Drug-Related Problems Occurring in Patients Receiving Outpatient Antimicrobial Therapy:

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.

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.

Pharmacy impact on medication reconciliation in the medical intensive care unit

Objective: Pharmacy-driven medication history (MH) programs have been shown to reduce the number of serious or potentially life-threatening (S/PLT) medication discrepancies (MDs) in many settings, but not Intensive Care Units (ICUs). Methods: MHs were repeated over a 6-week period. Demographics, number, and nature of MDs were documented. Discrepancy severity was graded using a previously published method. Primary outcome was the proportion of MHs containing >1 S/PLT MDs. Findings: Sixty-three MHs were repeated. Pharmacy MHs were less likely to contain ≥1 S/PLT MDs (0% vs. 50%, P < 0.001). Conclusion: Pharmacy MHs contained fewer S/PLT MDs in this small sample. S/PLT MDs on admission and home medication lists were common in patients admitted to the medical ICU. Pharmacy-driven medication reconciliation (MR) reduced the number and frequency of these discrepancies. Further research is required to improve current MR procedures.

Significant Hyperbilirubinemia and Acute Hepatocellular Jaundice in a Pediatric Patient Receiving Deferasirox: A Case Report

Despite a boxed warning, postmarketing reports of deferasirox-associated hepatic injury in patients with chronic transfusions are not well described. Hepatic impairment, including failure, has been reported to occur more frequently in patients older than 55 years and in those with significant comorbidities, including liver cirrhosis and multiorgan failure. In this case report, we describe significant hyperbilirubinemia and acute hepatocellular jaundice related to deferasirox in a 7-year-old female being treated for iron overload secondary to chronic transfusions. This report outlines a unique case without preexisting risk factors in which other causes of liver injury are excluded as defined by the Roussel Uclaf Causality Assessment Method, which indicates a probable score of deferasirox causing the injury.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection

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.

Impact of premix antimicrobial preparation and time to administration in septic patients.

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 patients 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.

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.

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.