Antibiotic stewardship bundle for uncomplicated gram-negative bacteremia at an academic health system: a quasi-experimental study.

Objective: To evaluate whether an antimicrobial stewardship bundle (ASB) can safely empower frontline providers in the treatment of gram-negative bloodstream infections (GN-BSI). Intervention and Method: From March 2021 to February 2022, we implemented an ASB intervention for GN-BSI in the electronic medical record (EMR) to guide clinicians at the point of care to optimize their own antibiotic decision-making. We conducted a before-and-after quasi-experimental pre-bundle (preBG) and post-bundle (postBG) study evaluating a composite of in-hospital mortality, infection-related readmission, GN-BSI recurrence, and bundle-related outcomes. Setting: New York University Langone Health (NYULH), Tisch/Kimmel (T/K) and Brooklyn (BK) campuses, in New York City, New York. Patients: Out of 1097 patients screened, the study included 225 adults aged ≥18 years (101 preBG vs 124 postBG) admitted with at least one positive blood culture with a monomicrobial gram-negative organism. Results: There was no difference in the primary composite outcome (12.9% preBG vs. 7.3% postBG; P = 0.159) nor its individual components of in-hospital mortality, 30-day infection-related readmission, and GN-BSI recurrence. Vancomycin (VAN) discontinuation (DC) was done more frequently by the primary team in postBG (37.9% vs 66.7%; P < 0.001). In postBG, de-escalation done by the primary team increased by 8.8%, P = 0.310 and there was an 11.1% increase in the use of aminopenicillin-based antibiotics, P = 0.043. Conclusions: GN-BSI bundle worked as a nudge-based strategy to guide providers in VAN DC and increased de-escalation to aminopenicillin-based antibiotics without negatively impacting patient outcomes.

Don't wait, vaccinate: evaluation of routine vaccination administration and reactogenicity in preterm infants.

OBJECTIVE: To evaluate the incidence of cardiorespiratory events in preterm infants when administering the 2-month vaccine series all at once compared to spreading vaccines over multiple days. STUDY DESIGN: This single-center, retrospective cohort study from 2019-2022 included preterm neonates receiving 2-month vaccinations. The primary outcome was incidence of cardiorespiratory events from time of initial vaccine administration up to 48 h after final administration. Univariate analysis was performed to identify predictors of primary outcome. RESULTS: There were 127 patients (pre-practice change n1 = 52, post-practice change n2 = 75) included with no difference in the number of cardiorespiratory events between groups. Predictors of severe event included younger gestational age, smaller birth weight, shorter birth length, and greater cardiorespiratory events at baseline. Vaccine schedule interruptions occur more often when administration is spread over multiple days. CONCLUSION: Administration of 2-month vaccinations all at once was not associated with increased cardiorespiratory events and prevents interruptions to vaccine schedule.

A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

BACKGROUND: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Evaluating the Use of Unfractionated Heparin with Intra-Aortic Balloon Counterpulsation.

BACKGROUND: Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. OBJECTIVES: The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). METHODS: This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. RESULTS: Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67-196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. CONCLUSIONS: We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting.

Evaluation of the Safety of Slow IV Push Versus Slow IV Infusion Administration of 23.4% Sodium Chloride.

Background and Purpose: Increased intracranial pressure due to cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Currently, safety data is limited on slow IV push (IVP) administration. The purpose of this study was to evaluate the safety of IVP administration of 23.4% NaCl and determine the number of infusion-related adverse events (IRAEs) compared to slow IV infusion (SIV) administration. Methods: We performed a retrospective review of patients who received a dose of 23.4% NaCl at the (removed institution) from January 2015 to June 2020 as either SIV over 30 minutes or IVP over 2-5 minutes. Results: In total, 81 patients, 55 in the IVP group and 26 in the SIV group, were included in the analysis. There was a significantly faster time from order entry to dose completion (IVP 25 [13,58] vs SIV 73 [55,113] minutes, P < .001). There was no difference in IRAEs between the groups (IVP 17 [31%] vs SIV 6 [23%], P = .466). Hypotension was most common (IVP 13 [24%] vs SIV 5 [19%], P = .656) followed by bradycardia (IVP 6 [11%] vs SIV 1 [4%], P = .291). There were no extravasations reported. Conclusions: Overall, among a cohort of patients with cerebral edema, we found no difference in the incidence of IRAEs between SIV and IVP administration of 23.4% NaCl, and found a faster time to complete administration fssor the latter. In emergent scenarios where time may impact neurologic function, 23.4% NaCl administered IVP may be an alternative to SIV administration.

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow Assay.

ABSTRACT: Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients who had percutaneous coronary intervention within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event. Secondary outcomes included VerifyNow platelet reactivity units (PRUs) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42%-45%), followed by NPO status (26%-28%) and MCS alone (22%-24%). The primary outcome of major adverse cardiovascular event occurred in 1 patient (1.1%). Of 92 patients, 77% had a P2Y12 level collected within 24 hours, and 89% of the cohort was able to achieve the goal P2Y12 PRU of <194. The median P2Y12 value within 24 hours of cangrelor initation was 115 PRU (40-168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients who received a drug-eluting stent in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer.

OBJECTIVE: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. RESULTS: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. CONCLUSIONS: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

The association of body mass index with tumor aggression among men undergoing radical prostatectomy.

OBJECTIVES: To evaluate the association of preoperative body mass index (BMI) on adverse pathology in peripheral (PZ) and transition zone (TZ) tumors at time of prostatectomy for localized prostate cancer. METHODS: Clinical and pathologic characteristics were obtained from up to 100 consecutive prostatectomy patients from 10 prostate surgeons. BMI groups included normal (18.5-24.9), overweight (25-29.9) and obese (> 29.9). "Aggressive" pathology was defined as the presence of Grade Group (GG) 3 or higher and/or pT3a or higher. Pathologic characteristics were evaluated for association with BMI using univariate analyses. Our primary outcome was the association of BMI with adverse pathology, which was assessed using logistic regression accounting for patient age. We hypothesized that obese BMI would be associated with aggressive TZ tumor. RESULTS: Among 923 patients, 140 (15%) were classified as "normal" BMI, 413 (45%) were "overweight", and 370 (40%) were "obese." 474 patients (51%) had aggressive PZ tumors while 102 (11%) had aggressive TZ tumors. "Obese" BMI was not associated with aggressive TZ tumor compared to normal weight. Increasing BMI group was associated with overall increased risk of aggressive PZ tumor (HR 1.56 [95CI 1.04-2.34]; P = 0.03). Among patients with GG1 or GG2, increasing BMI was associated with presence of pT3a or higher TZ tumor (P = 0.03). CONCLUSIONS: Increased BMI is associated with adverse pathology in PZ tumors. TZ adverse pathology risk may be increased among obese men with GG1 or GG2 disease, which has implications for future studies assessing behavioral change among men whose tumors are actively monitored.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Impact of oral vancomycin treatment duration on rate of Clostridioides difficile recurrence in patients requiring concurrent systemic antibiotics.

BACKGROUND: There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics. OBJECTIVES: To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. METHODS: In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE). RESULTS: Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11-14) and 20 days (16-26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). CONCLUSIONS: Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism.

INTRODUCTION: The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS: This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS: A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION: We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

A Case Report of Cardiac Arrest After Intravenous Administration of Sulfur Hexafluoride (Lumason®) Ultrasound Enhancing Agent.

Ultrasound enhancing agents (UEAs) are medications that enable clear visualization of ultrasound images. While large studies have demonstrated the safety of these agents, case reports of life-threatening reactions temporally associated with their use have been published and reported to the Food and Drug Administration. Current literature describes the most serious adverse reactions due to UEAs to be allergic in nature; however, embolic phenomena may play a role as well. Here, we report a case of unexplained cardiac arrest following the administration of sulfur hexafluoride (Lumason®) in an adult inpatient undergoing echocardiography where resuscitative efforts were ultimately unsuccessful, and review possible mechanisms of cardiac arrest based on prior published literature.

Treatment of Piperacillin-Tazobactam-Nonsusceptible/Ceftriaxone-Susceptible Infections With Carbapenem Versus Carbapenem-Sparing Antimicrobials.

Background: Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam-nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods: This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results: Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3-9] vs 6 [4-9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074-1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions: Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

Evaluation of Parenteral Potassium Supplementation in Pediatric Patients.

OBJECTIVE: The primary objective was to evaluate the effect of parenteral potassium chloride (KCl) supplementation on potassium (K+) concentrations in a non-cardiac pediatric population. Secondary outcomes were to identify variables that may influence response to KCl supplementation (i.e., change in K+ concentration after KCl administration) and assess the incidence of hyperkalemia. METHODS: This single-center, retrospective study evaluated infants and children who received parenteral KCl supplementation of 0.5 or 1 mEq/kg between January 2017 and December 2019. RESULTS: The study included 102 patients with a median age of 1 year (IQR, 0.4-3.9) and weight of 9.1 kg (IQR, 4.9-14.2) who received 288 parenteral KCl administrations. One hundred seventy-three administrations were in the 1 mEq/kg group, and 115 administrations were in the 0.5 mEq/kg group. The median changes in K+ were 0.8 and 0.5 mEq/L in the 1 mEq/kg and 0.5 mEq/kg groups, respectively. Patients who had a repeat K+ concentration within 4 hours of the end of a 1 to 2-hour infusion had a higher median change in K+ compared with those who had a concentration drawn after this time frame (0.8 vs 0.6 mEq/L; p < 0.01). CONCLUSIONS: There is a paucity of data on the correlation between parenteral KCl supplementation and change in K+ concentrations in pediatric patients. Our study demonstrated an association between KCl supplementation doses of 1 and 0.5 mEq/kg and changes in K+ of 0.8 and 0.5 mEq/L, respectively, in non-cardiac pediatric patients, with low observed incidence of hyperkalemia.

Quetiapine for the Treatment of Pediatric Delirium.

BACKGROUND: Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE: The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS: A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS: This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE: Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Novel Multidisciplinary Approach for Outpatient Antimicrobial Stewardship Using an Emergency Department Follow-Up Program.

Purpose: Outpatient antimicrobial stewardship programs (ASPs) are becoming increasingly prevalent in healthcare. Many programs have demonstrated the effectiveness of pharmacist-driven outpatient consultations or follow-up programs to ensure appropriate antimicrobial prescribing. However, there is a paucity of literature describing multidisciplinary approaches in large healthcare systems for patients discharged from the emergency department (ED). The objective of this study was to describe the feasibility and impact of a combined effort between ASP pharmacotherapy specialists and nurse practitioners (NPs) in managing an ED follow-up center. Methods: A retrospective analysis was conducted for patients discharged from the ED between January 2018 and June 2019. Patients were identified for inclusion based on documentation by ASP pharmacotherapy specialists in the electronic health record for patient-specific inquiries from ED follow-up center NPs. The primary outcome of this study was to describe the number and types of interventions made by ASP pharmacotherapy specialists. Results: A total of 1088 patients were included in the study, for 1114 documented ASP calls. The urinary tract was the most common source of positive culture (79%), and third-generation cephalosporins were the most frequent antibiotic associated with calls (20%). Out of total calls, 60% lead to ASP interventions. Among total calls, the most frequent interventions were to correct drug-bug mismatches (20%), initiate new therapy (10%), and discontinue therapy (7%). Conclusion: This report describes a novel initiative that combines the efforts of ED NPs and ASP pharmacotherapy specialists in managing an ED follow-up center at a large healthcare system.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.