Evaluation of Sequential Oral Versus Intravenous Antibiotic Treatment of Enterococcus faecalis Bloodstream Infections.

BACKGROUND: Intravenous (IV) antibiotics have historically been considered standard of care for treatment of bloodstream infections (BSIs). Recent literature has shown sequential oral (PO) therapy to be noninferior to IV antibiotics for certain pathogens and disease states. However, a gap exists in the literature for BSI caused by Enterococcus faecalis. OBJECTIVE: To compare outcomes of definitive sequential PO therapy to definitive IV therapy in patients with E faecalis BSI. METHODS: Multicenter, retrospective, matched cohort study of adult patients with at least one blood culture positive for E faecalis from January 2017 to November 2022. Patients with polymicrobial BSI, concomitant infections requiring prolonged IV antibiotic therapy, those who did not receive antibiotic therapy, and those who died within 72 hours of index culture were excluded. Subjects were matched based on source of infection in a 2:1 (IV:PO) ratio. The primary outcome was a composite of all-cause mortality and treatment failure. Secondary outcomes included hospital length of stay (LOS), antibiotic duration, and 30-day readmission rate. RESULTS: Of the 186 patients who met criteria for inclusion, there was no statistically significant difference in the primary composite outcome for PO compared to IV therapy (14.5% vs 21.8%; OR 0.53 [0.23-1.25]) or 30-day readmission (17.5% vs 29%; OR 0.53 [0.25-1.13]). Hospital LOS was significantly longer in patients receiving IV-only therapy (6 days vs 14 days; P < 0.001). CONCLUSION AND RELEVANCE: Sequential oral therapy for E faecalis BSI had similar outcomes compared to IV-only treatment and may be considered in eligible patients.

Development of Machine Learning Models to Validate a Medication Regimen Complexity Scoring Tool for Critically Ill Patients.

INTRODUCTION: The Medication Regimen Complexity -Intensive Care Unit (MRC-ICU) is the first tool for measuring medication regimen complexity in critically ill patients. This study tested machine learning (ML) models to investigate the relationship between medication regimen complexity and patient outcomes. METHODS: This study was a single-center, retrospective observational evaluation of 130 adults admitted to the medical ICU. The MRC-ICU score was utilized to improve the inpatient model's prediction accuracy. Three models were proposed: model I, demographic data without medication data; model II, demographic data and medication regimen complexity variables; and model III: demographic data and the MRC-ICU score. A total of 6 ML classifiers was developed: k-nearest neighbor (KNN), naïve Bayes (NB), random forest, support vector machine, neural network, and logistic classifier (LC). They were developed and tested using electronic health record data to predict inpatient mortality. RESULTS: The results demonstrated that adding medication regimen complexity variables (model II) and the MRC-ICU score (model III) improved inpatient mortality prediction.. The LC outperformed the other classifiers (KNN and NB), with an overall accuracy of 83%, sensitivity (Se) of 87%, specificity of 67%, positive predictive value of 93%, and negative predictive value of 46%. The APACHE III score and the MRC-ICU score at the 24-hour interval were the 2 most important variables. CONCLUSION AND RELEVANCE: Inclusion of the MRC-ICU score improved the prediction of patient outcomes on the previously established APACHE III score. This novel, proof-of-concept methodology shows promise for future application of the MRC-ICU scoring tool for patient outcome predictions.

Sepsis With Preexisting Heart Failure: Management of Confounding Clinical Features.

Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation followed by vasopressors (and potentially inotropes) if fluid is inadequate to restore perfusion; however, large fluid boluses and vasoactive agents are concerning amid the cardiac dysfunction of HF. This review summarizes evidence regarding the influence of HF on sepsis clinical outcomes, pathophysiologic concerns, resuscitation targets, hemodynamic interventions, and adjunct management (ie, antiarrhythmics, positive pressure ventilatory support, and renal replacement therapy) in patients with sepsis and preexisting HF. Patients with sepsis and preexisting HF receive less fluid during resuscitation; however, evidence suggests traditional fluid resuscitation targets do not increase the risk of adverse events in HF patients with sepsis and likely improve outcomes. Norepinephrine remains the most well-supported vasopressor for patients with sepsis with preexisting HF, while dopamine may induce more cardiac adverse events. Dobutamine should be used cautiously given its generally detrimental effects but may have an application when combined with norepinephrine in patients with low cardiac output. Management of chronic HF medications warrants careful consideration for continuation or discontinuation upon development of sepsis, and ß-blockers may be appropriate to continue in the absence of acute hemodynamic decompensation. Optimal management of atrial fibrillation may include ß-blockers after acute hemodynamic stabilization as they have also shown independent benefits in sepsis. Positive pressure ventilatory support and renal replacement must be carefully monitored for effects on cardiac function when HF is present.

Therapeutic Anticoagulation With an Ultra-Low Concentration Argatroban-Based Purge Solution for Percutaneous Ventricular Assist Device in Patient With Heparin-Induced Thrombocytopenia.

Purpose/Background: Percutaneous left ventricular assist devices (pVADs) require a continuous purge solution containing heparin to prevent pump thrombosis and device failure. Data regarding alternative options in patients who have suspected heparin-induced thrombocytopenia (HIT) are limited. Methods: In this report, we describe a 68-year-old white man with cardiogenic shock with an Impella CP device managed with a low concentration argatroban-based purge solution secondary to a suspected diagnosis of HIT. Results: The purge solution was initiated as argatroban in dextrose 10% at a concentration of 0.12 mg/mL and was subsequently decreased twice to 0.06 and 0.015 mg/mL based on the patient's clinical course. Conclusions: This case report describes the safe and effective use of argatroban purge solution necessary for anticoagulation although further studies are needed to confirm these findings.

Assessment of Electrolyte Replacement in Critically Ill Patients During a Drug Shortage.

Purpose: The purpose of this study was to determine if national drug shortages of electrolyte replacement products negatively impact patient care. Methods: This study was a single-center, retrospective, observational cohort of adults admitted to the medical, surgical, or trauma intensive care unit (ICU) that were ordered or would have qualified for the general or continuous renal replacement therapy electrolyte replacement protocol (ERP) between April 2017 and August 2018. In October 2017, ERP use was suspended and enteral replacement was promoted due to inability to maintain consistent inventory of intravenous replacement products. The primary objective was to compare the percentage of patient days that at least 1 critically low value of potassium, magnesium, and/or phosphorus existed between protocolized and nonprotocolized electrolyte replacement. Secondary objectives included characterizing the ratio of enteral replacement to duration of critically low electrolyte values during protocolized and nonprotocolized electrolyte replacement. Results: A total of 288 patients were included. The mean percentage of ICU days with low electrolyte levels in the protocolized period was significantly higher than in the nonprotocolized period (21.4% vs 17.5%, P = .0238). There was a negative relationship between the total electrolyte replacement that was given enterally and the percentage of patient days with critically low values indicating that as enteral replacement increased, percentage of days with low values decreased. The association between percentage of enteral replacement and days with critically low electrolyte values was significantly lower in the protocolized period. Conclusion: Intravenous electrolyte replacement product shortages did not result in an increased incidence of critically low electrolyte values. Enteral replacement was associated with a decreased incidence of low electrolyte values.

Patients with acute respiratory distress syndrome exhibit increased stromelysin1 activity in the blood samples.

Enzyme activity analyses in the blood are expected to be reliable, non-invasive diagnostic as well as prognostic markers to reflect disease progression in acute lung injury (ALI). The objective of the current study was to evaluate the enzymatic activity of stromelysin1 (matrix metalloprotease-3) in the plasma/serum samples collected from ALI patients compared to the samples collected from healthy controls. Gene expression omnibus (GEO) database analysis indicated a correlation between increased stromelysin1 gene expression and the incidence of ALI in various animal models. Our analysis of patient plasma/serum samples from healthy controls and ALI patients revealed a significant, 3-fold increase in stromelysin1 activity in ALI plasma/serum compared to healthy subjects with no difference in stromelysin1 activity between the serum and plasma samples. Interestingly, no significant difference in stromelysin1 activity between non-smoking and smoking subjects was observed. These findings provide fundamental information on the potential reliability of stromelysin1 activity analysis, combined with other biomarkers in development, in blood samples for the early detection of ALI.

Perioperative Bridging With Glycoprotein IIb/IIIa Inhibitors Versus Cangrelor: Balancing Efficacy and Safety.

OBJECTIVE: To review the efficacy and safety of perioperative administration of intravenous (IV) antiplatelet agents as a substitute for oral P2Y12 inhibitors and to provide clinicians guidance on optimal and cost-effective use of these medications. DATA SOURCES: A MEDLINE literature search (1950 to November 2018) was performed using the key search terms abciximab, bridging, cangrelor, cardiac surgery, coronary artery bypass surgery, eptifibatide, intravenous antiplatelet agent, and tirofiban. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: In all, 18 original research reports and case reports/series were included in the review. DATA SYNTHESIS: Prevention of postoperative bleeding is critical to decrease morbidity and mortality after cardiac surgery. IV antiplatelet medications have short half-lives and are frequently used to substitute for oral P2Y12 inhibitors to allow platelet function recovery before procedures. Functional recovery of platelets is delayed after abciximab discontinuation and increases postoperative bleeding risk. Eptifibatide and tirofiban have similar pharmacokinetic/pharmacodynamic properties and comparable efficacy and safety in the setting of perioperative bridging. Cangrelor may be considered in patients with renal insufficiency as decreased clearance of eptifibatide or tirofiban may increase the risk of postoperative bleeding. Relevance to Patient Care and Clinical Practice: Comparative studies of IV antiplatelet medications have not been published. Appropriate use of IV antiplatelet medications can prevent perioperative ischemic events and bleeding. CONCLUSIONS: Eptifibatide, tirofiban, and cangrelor are preferred over abciximab as a perioperative bridge. The choice of agent should be tailored to clinical characteristics of the patient and institutional acquisition costs.

Prescribing of Pressor Agents in Septic Shock: A Survey of Critical Care Pharmacists.

Background: Pressor agents are recognized as high-alert medications by the Institute for Safe Medication Practices, but little evidence is available to guide their use in septic shock. Objective: Characterize the use of pressor agents for septic shock in clinical practice. Methods: A cross-sectional electronic survey assessing demographics, institutional practices, and respondent perceptions related to pressor agents was distributed to the American College of Clinical Pharmacy Critical Care Practice and Research Network. The primary outcome was the use of a weight-based dosing (WBD) strategy versus non-WBD strategy for norepinephrine. Descriptive statistics were used to summarize survey results. Binary logistic regression was performed to determine variables associated with dosing strategies. Results: The survey was completed by 223 respondents. The typical respondent worked in a medical or mixed intensive care unit at a teaching hospital and had training and/or board certification beyond the Doctor of Pharmacy degree. Nearly all respondents (n = 221, 99%) reported norepinephrine as the first-line vasopressor for septic shock; however, 38% used WBD and 60% used non-WBD. In logistic regression, respondents located in the South and practicing at institutions with larger numbers of intensive care unit beds were more likely to use WBD for norepinephrine infusions. Similar findings were observed with epinephrine and phenylephrine. Conclusion: Wide variability exists in prescribing patterns of pressor agents and in pharmacist perceptions regarding best practices. The use of WBD varied based on institutional characteristics and resulted in higher maximum allowable infusion rates of pressor agents. Future research should compare dosing strategies to identify associations with patient outcomes.

Complications and Pharmacologic Interventions of Invasive Positive Pressure Ventilation During Critical Illness.

Objective: To review the fundamentals of invasive positive pressure ventilation (IPPV) and the common complications and associated pharmacotherapeutic management in order to provide opportunities for pharmacists to improve patient outcomes. Data Sources: A MEDLINE literature search (1950-December 2017) was performed using the key search terms invasive positive pressure ventilation, mechanical ventilation, pharmacist, respiratory failure, ventilator associated organ dysfunction, ventilator associated pneumonia, ventilator bundles, and ventilator liberation. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language original research and review reports were evaluated. Data Synthesis: IPPV is a common supportive care measure for critically ill patients. While lifesaving, IPPV is associated with significant complications including ventilator-associated pneumonia, sinusitis, organ dysfunction, and hemodynamic alterations. Optimization of pain and sedation management provides an opportunity for pharmacists to directly affect IPPV exposure. A number of pharmacotherapeutic interventions are related directly to prophylaxis against IPPV-associated adverse events or aimed at reduction of duration of IPPV. Conclusions: Enhanced knowledge of the common complications, associated pharmacotherapy, and monitoring strategies facilitate the pharmacist's ability to provide increased pharmacotherapeutic insight in a multidisciplinary intensive care unit setting.

A descriptive report of the rapid implementation of automated MRC-ICU calculations in the EMR of an academic medical center.

PURPOSE: Numerous clinical scoring tools exist for a variety of patient populations and disease states, but few tools provide information specifically designed for use by critical care pharmacists. The medication regimen complexity-intensive care unit (MRC-ICU) score was designed to provide high-level information about the complexity of critically ill patients' medication regimens for use by critical care pharmacists. To date, implementation of this score in the electronic medical record (EMR) has not been reported. SUMMARY: Using an agile project management framework, the MRC-ICU score was rapidly implemented into an academic medical center's EMR. The score is automatically calculated for all critically ill patients and is available for critical care pharmacists to triage patient review in their individual workflow. Reporting capabilities of the score also allow for granular complexity trending over time and between units, supplementing other objective measures of pharmacist workload. CONCLUSION: The MRC-ICU score can be quickly implemented into the EMR for pharmacist use in real time. Future investigations into how pharmacists utilize this information and how to harness reporting capabilities for pharmacist workload assessment are warranted.

Medication Regimen Complexity Score as an Indicator of Fluid Balance in Critically Ill Patients.

BACKGROUND: Critically ill patients are at increased risk for fluid overload, but objective prediction tools to guide clinical decision-making are lacking. The MRC-ICU scoring tool is an objective tool for measuring medication regimen complexity. OBJECTIVE: To evaluate the relationship between MRC-ICU score and fluid overload in critically ill patients. METHODS: In this multi-center, retrospective, observational study, the relationship between MRC-ICU and the risk of fluid overload was examined. Patient demographics, fluid balance at day 3 of ICU admission, MRC-ICU score at 24 hours, and clinical outcomes were collected from the medical record. The primary outcome was relationship between MRC-ICU and fluid overload. To analyze this, MRC-ICU scores were divided into tertiles (low, moderate, high), and binary logistic regression was performed. Linear regression was performed to determine variables associated with positive fluid balance. RESULTS: A total of 125 patients were included. The median MRC-ICU score at 24 hours of ICU admission for low, moderate, and high tertiles were 9, 15, and 21, respectively. For each point increase in MRC-ICU, a 13% increase in the likelihood of fluid overload was observed (OR 1.128, 95% CI 1.028-1.238, p = 0.011). The MRC-ICU score was positively associated with fluid balance at day 3 (ß-coefficient 218.455, 95% CI 94.693-342.217, p = 0.001) when controlling for age, gender, and SOFA score. CONCLUSIONS: Medication regimen complexity demonstrated a weakly positive correlation with fluid overload in critically ill patients. Future studies are necessary to establish the MRC-ICU as a predictor to identify patients at risk of fluid overload.

Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function.

BACKGROUND: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. OBJECTIVE: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. METHODS: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. RESULTS: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. CONCLUSION: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Fluid Stewardship of Maintenance Intravenous Fluids.

Despite the frequent use of maintenance intravenous fluids (mIVF) in critically ill patients, limited guidance is available. Notably, fluid overload secondary to mIVF mismanagement is associated with significant adverse patient outcomes. The Four Rights (right drug, right dose, right duration, right patient) construct of fluid stewardship has been proposed for the safe evaluation and use of fluids. The purpose of this evidence-based review is to offer practical insights for the clinician regarding mIVF selection, dosing, and duration in line with the Four Rights of Fluid Stewardship.