State of the Management of Infections Caused by Multidrug-Resistant Gram-Negative Organisms.

In the past decade, the prevalence of multidrug-resistant gram-negative (MDR-GN) bacterial infections has increased significantly, leading to higher rates of morbidity and mortality. Treating these infections poses numerous challenges, particularly when selecting appropriate empiric therapy for critically ill patients for whom the margin for error is low. Fortunately, the availability of new therapies has improved the treatment landscape, offering safer and more effective options. However, there remains a need to establish and implement optimal clinical and therapeutic approaches for managing these infections. Here, we review strategies for identifying patients at risk for MDR-GN infections, propose a framework for the choice of empiric and definitive treatment, and explore effective multidisciplinary approaches to managing patients in the hospital while ensuring a safe transition to outpatient settings.

An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers.

BACKGROUND: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. RESEARCH QUESTION: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? STUDY DESIGN AND METHODS: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. RESULTS: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. INTERPRETATION: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics.

Managing toxicities associated with immune checkpoint inhibitors.

ABSTRACT: Recent development of immunotherapy has led to remarkable advancement in cancer therapy. Drugs that inhibit the cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1) immune checkpoint pathways have shown improved patient survival. However, by altering the immune response to fight cancer, a new class of adverse reactions has emerged, known as immune-related adverse events. These adverse events are due to overactivation of the immune system in almost any organ of the body, can occur at any point in a patient's treatment course, and may become life-threatening. This article describes how to promptly recognize and manage these toxicities.

Stevens-Johnson Syndrome Associated With Chlordiazepoxide.

Objective: To report a case of chlordiazepoxide-associated Stevens-Johnson syndrome (SJS). Case Summary: This case provides insight into a serious adverse drug reaction secondary to a drug not commonly associated with SJS. A 29-year-old female presented with a 4-day history of rash and pruritus. The rash started on her arms and spread all over her body. The patient was started on chlordiazepoxide 3½ weeks ago. On examination, there were multiple, raised, round erythematous lesions in various stages of healing. Skin erosions were noted on her lips and buccal mucosa. However, the rash did not involve the conjunctiva, inner ears, or genitalia. The patient was discharged home with a follow-up appointment with dermatology and instructions to discontinue chlordiazepoxide. Two days after her initial presentation, the patient's rash spread to her eyes and genitalia. A painful, white film developed on her tongue, and she was unable to tolerate oral intake. She was emergently sent back to hospital and transferred to a Burn Unit. The biopsy report revealed full-thickness necrotizing keratinocytes in the epidermis consistent with SJS. Discussion: To our knowledge, there is only one other case report of chlordiazepoxide-associated SJS. Chlordiazepoxide is thought to be the cause of this patient's biopsy-confirmed SJS and overall presentation. SJS is a rare but serious condition that is usually a result of drug exposure. Conclusions: The close temporal relationship between chlordiazepoxide initiation and onset of SJS provides a convincing theory as to the etiology of SJS in our patient.

Recommendations From the 2016 Guidelines for the Management of Adults With Hospital-Acquired or Ventilator-Associated Pneumonia.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to represent the most common nosocomial-associated infections, resulting in significant attributable mortality, increased length of hospital stay, and financial burden.1 The updated Infectious Diseases Society of America (IDSA) guidelines provide guidance on the diagnosis and management of nonimmunocompromised hosts with HAP and VAP.

Management of Hepatic Encephalopathy: A Primer.

OBJECTIVE: To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. DATA SOURCES: A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis All published articles evaluating treatments for HE were considered. STUDY SELECTION AND DATA EXTRACTION: Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS: HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. CONCLUSION: Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Potassium-Binding Agents for the Clinical Management of Hyperkalemia.

Use of sodium polystyrene sulfonate (SPS) dominates the long-term treatment of hyperkalemia, but two new agents, sodium zirconium cyclosilicate and the recently FDA-approved patiromer, may offer potential advantages compared with SPS.

Mepolizumab (Nucala) For Severe Eosinophilic Asthma.

Mepolizumab (Nucala) for severe eosinophilic asthma.

Pharmacological Management and Prevention Of Exacerbations of Chronic Obstructive Pulmonary Disease in Hospitalized Patients.

Rapid-acting bronchodilators, systemic corticosteroids, and antibiotics are among the keys to managing exacerbations of chronic obstructive pulmonary disease. Preventing exacerbations should also be a component of therapy for the disease.

Topiramate-Related Hyperammonemia.

Objective: To report a case of hyperammonemia associated with the interaction between topiramate and valproic acid. Case Summary: We present a patient case with topiramate-related hyperammonemia. The patient was on topiramate prior to admission and presented with an elevated ammonia level following 2 doses of valproic acid. The increased dosing frequency of valproic acid further exacerbated the hyperammonemia. On discontinuation of topiramate and the tapering of the dose of valproic acid the patient's ammonia level returned to normal. Discussion: Valproic acid-induced hyperammonemic encephalopathy is well documented and there are several proposed mechanisms. The interaction between valproic acid and topiramate causing drug-induced hyperammonemia encephalopathy is documented in several case reports. The interaction is associated with the addition of topiramate to a patient's medication regimen that previously included valproic acid. Topiramate also has several proposed mechanisms for predisposing patients for hyperammonemia. There are limited data on topiramate monotherapy or long-term use of topiramate use causing hyperammonemia-associated encephalopathy or enhancing hyperammonemia with the addition of valproic acid. Conclusions: This case supports topiramate-related hyperammonemia and the pharmacodynamic interaction with the co-administration of valproic acid.

Pharmacologic management of chronic stable angina.

Chronic stable angina is a significant problem in older adults. The goal of therapy is to provide symptomatic relief, improve patient quality of life, and prevent subsequent angina or myocardial infarction that could lead to sudden death. The efficacy and safety of drugs such as beta-blockers and calcium channel blockers for managing chronic stable angina in older adults has not been rigorously investigated. Drug selection should be based on physiologic alterations, patient comorbidities, adverse reaction profile, and cost.

Critical care pharmacist perspectives on optimal practice models and prioritization of professional activities: A cross-sectional survey.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Critical care pharmacists (CCPs) are essential members of the multidisciplinary critical care team. Professional activities of the CCP are outlined in a 2020 position paper on critical care pharmacy services. This study looks to characterize CCP perspectives for priorities in optimizing pharmacy practice models and professional activities. METHODS: This was a cross-sectional survey conducted from July 24 to September 20, 2023. A 41-question survey instrument was developed to assess 7 domains: demographics, CCP resource utilization, patient care, quality improvement, research and scholarship, training and education, and professional development. This voluntary survey was sent to members of the American College of Clinical Pharmacy's Critical Care Practice and Research Network. The survey was open for a total of 6 weeks. RESULTS: There was a response rate of 20.7% (332 of 1,605 invitees), with 66.6% of respondents (n = 221) completing at least 90% of the survey questions. Most respondents were clinical specialists (58.2%) and/or practiced at an academic medical center (58.5%). Direct patient care, quality improvement and medication safety, and teaching and precepting were identified as the CCP activities of highest importance to CCPs. The CCP-to-patient ratios considered ideal were 1:11-15 (selected by 49.8% of respondents) and 1:16-20 (33.9% of respondents). The ideal percentage of time dedicated to direct patient care activities, as identified by survey respondents, was 50% (interquartile range, 40-50). CONCLUSION: These findings highlight the professional activities viewed as having the highest priority by CCPs. Future research is needed to define optimal CCP practice models for the delivery of patient care in real-world settings.

Risk Factors and Clinical Outcomes of Candidemia Associated With Severe COVID-19.

COVID-19 can cause serious illness requiring multimodal treatment and is associated with secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear. OBJECTIVES: To describe clinical characteristics, outcomes and risk factors of candidemia among patients hospitalized with severe COVID-19. DESIGN SETTING AND PARTICIPANTS: A multicenter, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 and August 2021. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, clinical and mycological characteristics, concomitant interventions (antibiotics, immunosuppressive agents, parenteral nutrition, degree of oxygen support, mechanical ventilation, surgery), treatment regimens, and outcomes (length of stay and discharge disposition). RESULTS: A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of patients received biologic for COVID-19. In-hospital mortality was significantly higher in the cases compared with the controls (68% vs 40%; p < 0.01). Candida albicans was the most common (53%), followed by C. glabrata (19%). Use of central lines, biologic, and paralytics were independent risk factors for candidemia. CONCLUSIONS AND RELEVANCE: Candidemia following COVID-19 infection is a concern that requires clinical consideration and patient monitoring. Risk factors for the development of candidemia in the setting of COVID-19 infection are largely consistent with traditional risk factors for candidemia in hospitalized patients.

Multicenter Retrospective Review of Ketamine Use in the ICU.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study. CONCLUSIONS AND RELEVANCE: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Descriptive analysis of the unwarranted continuation of antipsychotics for the management of ICU delirium during transitions of care: A multicenter evaluation across New Jersey.

PURPOSE: Nearly half of intensive care unit (ICU) patients will develop delirium. Antipsychotics are used routinely for the management of ICU delirium despite limited reliable data supporting this approach. The unwarranted continuation of antipsychotics initiated for ICU delirium is an emerging transitions of care concern, especially considering the adverse event profile of these agents. We sought to evaluate the magnitude of this issue across 6 centers in New Jersey and describe risk factors for continuation. METHODS: This multicenter, retrospective study examined adult ICU patients who developed ICU delirium from June 2016 to June 2018. Patients were included in the study if they received at least 3 doses of antipsychotics while in the ICU with presence of either a clinical diagnosis of delirium or a positive Confusion Assessment Method score. Patients were excluded if they were on an antipsychotic before ICU admission. RESULTS: Of the 300 patients included and initiated on antipsychotics for ICU delirium, 157 (52.3%) were continued on therapy upon transfer from the ICU to another level of inpatient care. The number of patients continued on newly initiated antipsychotics further increased to 183 (61%) upon discharge from the hospital. CONCLUSION: The continuation of antipsychotics for the management of delirium during transitions of care was a common practice across ICUs in New Jersey. Several risk factors for continuation of antipsychotics were identified. Efforts to reduce unnecessary continuation of antipsychotics at transitions of care are warranted.

Implementation and evaluation of a virtual learning advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 restricted student involvement in direct patient care. Virtual learning is an effective education strategy in pharmacy curriculums. This study aimed to evaluate student perceptions of virtual learning advanced pharmacy practice experiences (APPE) utilizing an electronic 12-question survey. EDUCATIONAL ACTIVITY AND SETTING: Virtual learning was developed and implemented, and students were surveyed at the end of the APPE. The survey was comprised of one open-ended and 11 Likert scale questions. It assessed implementation and use of virtual learning in place of a standard on-site APPE. FINDINGS: Responses were attained from 19 students. Questions regarding resources provided and virtual learning enabling autonomous, independent learning had the highest percent of strong agreement. No responses indicated strong disagreement. Three questions solicited >10% response rate of somewhat disagree, 16% associated with virtual learning helping the student become a better member of the healthcare team after graduation. Open-ended responses acknowledged appreciation of the virtual APPE and presented material. One in six students commented on the ability to apply the learned information to direct patient care. Feedback was delivered on consideration for increased utility of patient care-orientated applications to facilitate simulation of real-life patient cases. SUMMARY: Students who completed the virtual APPE were satisfied overall. Virtual teaching modalities may be incorporated into APPEs, particularly when direct patient care access is limited, but should not be used to completely replace the experience gained during direct patient care.

Integrating high fidelity patient simulation into a skills-based doctor of pharmacy curriculum: A literature review with focus on the bedrock pilot course.

INTRODUCTION: Simulation-based teaching is an effective instructional strategy gaining momentum in pharmacy education but remains variable across programs. This is the first known report depicting the development of a multifaceted, integrated simulation program during concurrent initiation of a new skills-based pharmacy curriculum. METHODS: A significant infrastructure expansion created simulation areas whose availability corresponded with the initiation of a new skills-based curriculum. Integration of simulation occurred with existing personnel resources using area pilots. Pilots developed operational and educational design standards spanning the pre-simulation, simulation, and debriefing phases. The value of high-fidelity simulation pilots detailed here was assessed through both student survey and successful transference of tools to other courses. RESULTS: The pilots developed core operational and educational design standards, super-user faculty groups, and created an operational director position, essential for simulation promulgation throughout the curriculum. In the high-fidelity patient simulation pilot, operational elements included mannequin and equipment procedures, best practices for faculty and confederate engagement, and formulary development. Educational design standards addressed objective development, session flow, team roles, and debriefing. A grading rubric template aligned goals and assessed outcomes. All elements were structured into a planning worksheet. Student survey reflected the perceived value of this pilot. CONCLUSIONS: Operational support, integration coordination, and perceived value are all essential elements for successful curricular integration of simulation in a pharmacy curriculum. The pilots created the operational and educational structure establishing standards and defining required resources to sustain success. These pilots allowed for rapid curricular proliferation of simulation across the first and third professional years.