Methadone-Induced Hypoglycemia in a Hospitalized Patient.

Methadone is used as an agent for chronic pain and management of opioid use disorder. While similar pharmacologically to other opioids, methadone does have unique characteristics, including long half-life, low cost, and high oral bioavailability. While advantageous in some ways, methadone is associated with unique adverse effects not seen with other opioids (ie, hypoglycemia). In this case, we describe a patient in his late-60s with opioid use disorder on chronic methadone who presents with symptoms of generalized weakness, fatigue, and decreased appetite for 2 days. The hospital course was complicated by hypoglycemia, without obvious cause other than methadone-induced hypoglycemia. The patient was managed with supportive care to maintain normoglycemia. He was continued on methadone and instructed to follow-up with his opioid treatment program to assess for dose de-escalation to minimize future hypoglycemia risk. While other case reports of methadone-induced hypoglycemia highlight the risk of this adverse effect, our case highlights the importance of assessing methadone as a cause of hypoglycemia and provides discussion around the legality of dose de-escalation at discharge from an acute care setting.

Hydroxychloroquine-Induced Hypoglycemia in a Patient Without Diabetes.

Hydroxychloroquine is a disease-modifying antirheumatic drug commonly used in the treatment of autoimmune diseases. Although rare, hydroxychloroquine is associated with hypoglycemia in patients with or without diabetes due to its ability to alter insulin metabolism. There have been several cases described in the literature, but none of which, to our knowledge, detail follow-up and time to resolution of hypoglycemia. We describe a 55-year-old female who presents for episodes of hypoglycemia. She reported hypoglycemic symptoms and fasting blood glucoses in the 60-70s mg/dL regularly. Based on the Naranjo adverse drug reaction probability scale, hydroxychloroquine was the probable etiology of her hypoglycemic episodes due to the improvement at her 3-month follow up appointment after discontinuing the drug. Providers should be mindful of the hypoglycemia risk when using hydroxychloroquine and be aware that the effects may take an extended amount of time to resolve given the drug's long half-life.

Use of antithymocyte globulin (rabbit) in a patient with known alpha-gal syndrome undergoing allogenic stem cell transplantation.

INTRODUCTION: Alpha-gal syndrome (AGS) is a hypersensitivity disorder in which tick bites-most commonly from the lone star tick (Ambylomma americanum)-trigger immunoglobulin E-mediated hypersensitivity reaction upon exposure to oligosaccharide galactosse-alpha-1,3-galactose (α-gal). α-gal is most notorious for being found in "red meat" products but is present in mammalian meats such as beef, pork, lamb, rabbit, and others. Manifestations of AGS hypersensitivity are variable. There is currently no in vivo data describing allergic reactions against rabbit products in patients with AGS. CASE REPORT: Here, we describe a case of a 44-year-old male with myelodysplastic syndrome and a known history of AGS undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) with the use of rabbit antithymocyte globulin (rATG) for graft-versus-host disease (GVHD) prophylaxis. MANAGEMENT AND OUTCOME: The risk of cross-reactivity against rATG in our patient with AGS could not be ruled out and, therefore, a test dose was administered. The patient tolerated the test dose with no signs of anaphylaxis. After demonstrating tolerance to the test dose, rATG was utilized for GVHD prophylaxis. DISCUSSION: Due to the heterogeneity of AGS manifestations in patients, the use of rATG in patients with known AGS should be considered on a case-by-case basis. The administration of a test dose may help predict the occurrence of severe hypersensitivity reactions. The limited data surrounding the risk of AGS with rabbit-containing products and the various indications for the use of rATG warrants more in-depth study of the reactivity of this medication in this population.

Missed Antimicrobial Stewardship Opportunities for Hospitalized Patients with Urinary Tract Infections Receiving Ceftriaxone.

Background: Ceftriaxone is a commonly utilized antibiotic for the treatment of urinary tract infections (UTI) despite the limited literature supporting its use. Opportunities for antimicrobial stewardship (ASP), including IV-to-PO conversions and de-escalation of therapy, are often missed in the hospital setting. Objective: The study reported here describes the utilization of ceftriaxone in patients admitted to the hospital and treated for UTIs in a large health system, focusing on opportunities for IV-to-PO conversion of antibiotic therapy. Methods: This was a multi-center, retrospective, descriptive study conducted in a large health system. Patients admitted from January 2019 to July 2019 were included for analysis if they were 18 years or older at admission, diagnosed with acute cystitis, acute pyelonephritis, or unspecified UTI, and received two or more doses of ceftriaxone. The primary outcome was to evaluate the percentage of patients who were eligible for conversion from IV ceftriaxone to oral antibiotics while admitted to the hospital based on the defined criteria for automatic pharmacist conversion in the health system. Percentage of urine cultures with susceptibility to cefazolin, the duration of antibiotic therapy in the hospital, and an evaluation of oral antibiotics prescribed at discharge were also recorded. Results: A total of 300 patients were included; 88% met the pre-specified criteria for IV-to-PO conversion, but only 12% were converted from IV-to-PO antibiotics during hospitalization. Approximately 65% of patients remained on IV ceftriaxone until discharge, at which time they were converted to a PO antibiotic, most commonly fluoroquinolones followed by third-generation cephalosporins. Conclusion: Patients admitted to the hospital and receiving treatment with ceftriaxone for UTI were infrequently converted to oral therapy prior to discharge despite meeting criteria for automatic pharmacist IV-to-PO conversion. Findings highlight opportunities to contribute to antimicrobial stewardship initiatives across the health system and the importance of tracking and reporting results to frontline providers.

Can't keep it SECRET: system evaluation of carbapenem restriction against empirical therapy.

Objectives: Carbapenems are appealing agents for empirical use given their broad spectrum of activity; however, selective use is vital in minimizing the risk for development of carbapenem-resistant pathogens. We aimed to examine the impact of carbapenem restriction criteria and a pre-authorization process on utilization and cost savings across a health system. Methods: This retrospective study was conducted across five adult hospitals. The pre-implementation period was 8 February 2020 to 30 April 2020 and the post-implementation period was 8 February 2022 to 30 April 2022. The primary outcome was to compare the number of orders for carbapenems between the study periods for both the intervention and non-intervention hospitals. Secondary outcomes included projected annual cost and an estimated cost-savings evaluation using a stratified analysis for the intervention and non-intervention facilities to account for more resource-limited settings. Results: The total number of carbapenem orders decreased between study periods at the intervention hospital (246 versus 61, P < 0.01). At the non-intervention hospitals, orders decreased, although not significantly (333 versus 279, P = 0.58). Meropenem orders decreased by 66% compared with 12% for the intervention and the non-intervention hospitals, respectively (P < 0.001). Annual estimated cost for all facilities was $255 561 in the pre-implementation period compared with $29 593 in the post-implementation period (P < 0.001). Using a stratified analysis to account for available resources, the estimated annual cost saving was $225 968 for the system. Conclusions: Implementation of carbapenem restriction at the intervention hospital decreased utilization and provided significant cost savings. Furthermore, resource-limited facilities can still experience significant cost savings using a stratified antimicrobial stewardship intervention approach.

A Review of Current and Emerging Therapeutic Options for Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: To provide an overview of clinical sequelae and emerging treatment options for hemophagocytic lymphohistiocytosis (HLH). DATA SOURCES: A literature search was conducted using the search terms "hemophagocytic lymphohistiocytosis," "hemophagocytic syndrome," "macrophage activation syndrome," and "treatment" on Ovid and PubMed from January 1, 2017, through September 28, 2022. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials, meta-analyses, case reports, review articles, package inserts, and guidelines to identify current and emerging therapeutic options for the management of HLH. DATA SYNTHESIS: Genetic disorders and secondary causes may trigger HLH in both children and adults. Notable improvements in the diagnosis of HLH were seen with implementation of the HLH-2004 standard diagnostic criteria; however, timely and accurate identification of HLH remain significant barriers to optimal management. Multiagent immunochemotherapy are the backbone of aggressive therapy for acutely ill patients with HLH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The global coronavirus 2019 (COVID-19) pandemic and emerging immune effector cell therapies have served to highlight the concerns with immune dysregulation and subsequent HLH precipitation. Without prompt identification and treatment, HLH can be fatal. Historically, the clinician's armamentarium for managing HLH was sparse, with etoposide-based protocols serving as the standard of care. Relapsed or refractory disease portends a poor prognosis and requires additional treatment options. Second- or subsequent-line options now include hematopoietic stem cell transplantation, emapalumab, alemtuzumab, anakinra, ruxolitinib, and tocilizumab. CONCLUSIONS: Improvements in diagnostic methods and novel immunosuppressive treatment strategies, including noncytotoxic immunochemotherapy, have transformed the therapeutic landscape. Unfortunately, many unanswered questions remain. Additional studies are required to optimize dosing, schedules, treatment sequences, and indications for novel treatment options.

Safety of early antiplatelet administration in patients with acute ischemic stroke treated with alteplase (SEAPT-24).

OBJECTIVES: Alteplase, a tissue-type plasminogen activator, is recommended for ischemic stroke patients presenting within 4.5 h. Due to bleeding risks, current guidelines advise delaying antiplatelet therapy for 24 h after alteplase. However, specific scenarios may require antiplatelet therapy to be given within the 24 h window. This study aimed to examine the safety of early antiplatelet therapy administration within the first 24 h after alteplase. MATERIALS AND METHODS: This study is a retrospective, observational study of adult patients with acute ischemic stroke who received alteplase across a multi-hospital system. Patients were grouped based on early antiplatelet therapy (within 24 h window) or as recommended per guidelines. The occurrence of bleeding events, including symptomatic intracranial hemorrhage and/or gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes (modified Rankin score 3-6), and hospital length of stay, were compared between groups. RESULTS: Patients were predominantly African American (72%) and female (53%) with a median age of 62 years. Median baseline NIHSS scores were higher in the early group (5 vs. 7; p = 0.04), and patients in the early group were more likely to undergo endovascular therapy (26% vs. 8%, p < 0.0001). In patients treated with alteplase only and who did not undergo endovascular therapy, there was no difference in symptomatic intracranial hemorrhage (1.4% vs. 0%, p = 0.1), gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes, or length of stay. CONCLUSIONS: In our retrospective analysis, early administration of antiplatelet therapy (< 24 h post-alteplase) did not increase the risk of symptomatic intracranial hemorrhage, gastrointestinal bleeding, or unfavorable outcomes in patients who received alteplase alone for management of acute ischemic stroke. Prospective studies are needed to validate these findings.

Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): a quasi-experimental carbapenem restriction pilot at a large academic medical centre.

The broad-spectrum activity of carbapenems makes them appealing for empirical use; however, they are associated with development of Clostridioides difficile infection (CDI) and multidrug resistance. Selective carbapenem use is vital in maintaining their effectiveness. We examined the impact of meropenem restriction criteria on utilisation and patient outcomes. This quasi-experimental study was conducted at a single academic medical centre after medication use evaluation found frequent inappropriate meropenem utilisation. Antimicrobial stewardship-led restriction criteria were developed and implemented in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilisation across 8 weeks in the pre- (February-April 2020) versus post-implementation period (February-April 2022). The primary outcome was inappropriateness of meropenem utilisation. Secondary outcomes included days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), CDI Standardized Infection Ratio (SIR), and acquisition cost. Across the 8-week timeframes, reductions in inappropriate meropenem use (64.5% vs. 12.8%; P < 0.001), duration of therapy [5.8 (3.2-7.3) vs. 2.4 (1.0-5.5) days; P < 0.001] and utilisation (30.5 vs. 8.3 DOT/1000 PD; P < 0.001) pre- versus post-implementation were observed. Total meropenem orders decreased by 65% (P < 0.001). Median hospital LOS also decreased between periods [11.9 (7.8-20.4) vs. 9.2 (5.4-15.2) days], although not statistically significant (P = 0.051). There was no difference in CDI SIR (0.1 vs. 0.1; P = 0.99). Projected annual cost savings were ∼US$57 300. Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate meropenem utilisation, overall number of orders, and total duration of therapy.

Gabapentinoid dosing and adverse events in patients with chronic kidney disease.

BACKGROUND: Gabapentinoids (GPs) are frequently prescribed in individuals with chronic kidney disease (CKD); however, their exclusive renal elimination warrants dose adjustments to decrease risk of toxicity. This study evaluated GP prescribing patterns and whether excessive dosing was associated with increased incidence of gabapentinoid-related adverse events (GRAEs). MATERIALS AND METHODS: A retrospective analysis of adult CKD and end-stage kidney disease (ESKD) patients hospitalized from 2014 to 2020 and receiving GPs was conducted. Patients were grouped based on whether the average daily dose prescribed was higher than recommended (inappropriately dosed, (ID)) or as recommended (appropriately dosed (AD)) for CKD stage. The occurrence of GRAEs was compared between groups. Patient characteristics, CKD stage, and hospital length of stay (LOS) were evaluated to determine association with GRAEs. RESULTS: The 200 patients included were predominantly female (51%), black (72%), CKD 5/ESKD (84%), and prescribed gabapentin (90%) with a mean age 61 ± 14 years. For the 111 (55%) patients in the AD group and 89 (45%) in the ID group there was no statistically significant difference in GRAEs (18 vs. 19%, p = 0.84). GRAEs were associated with older age (66 vs. 61 years; p < 0.001), seizure history (14% for GRAE vs. 3% for no GRAE, p = 0.02), and concomitant antipsychotic use (24% for GRAE vs. 5% for no GRAE; p < 0.001) but not with CKD severity. LOS was significantly longer for patients experiencing a GRAE (8.5 vs. 5.3 days; p < 0.001). CONCLUSION: Appropriate dosing of GPs is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use. There is a need for prescriber education given the high frequency of inappropriate GP dosing observed in patients with advanced kidney disease.