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Asymptotic results for the Euclidean minimal spanning tree on n random vertices in Rd can be obtained from consideration of a limiting infinite forest whose vertices form a Poisson process in all Rd. In particular we prove a conjecture of Robert Bland: the sum of the d'th powers of the edge-lengths of the minimal spanning tree of a random sample of n points from the uniform distribution in the unit cube of Rd tends to a constant as n→∞. Whether the limit forest is in fact a single tree is a hard open problem, relating to continuum percolation. © 1992 Springer-Verlag.

Background: Many Postgraduate Year One (PGY1) Pharmacy residencies provide research training however, details of this training are not well described. Publication rates have been utilized to assess residency research learning experiences. Higher publication rates have been reported by programs that have implemented a structured research learning experience. Objective: The primary objective was to identify differences in the research learning experiences for American Society of Health-System Pharmacists (ASHP) accredited PGY1 Pharmacy residencies with reported resident publication rates of ≥20% vs <20%. Methods: This survey was distributed to PGY1 Pharmacy residency program directors (RPDs). Seven sections were analyzed to identify research learning experience differences between programs with reported publication rates of ≥20% vs <20%: (1) program characteristics/research outcomes; (2) involved individuals; (3) requirements; (4) learning experience structure; (5) educational methods; (6) formal education; (7) barriers/RPD perceptions. Variables with P < 0.05 on logistic regression were considered statistically significant. Results: The survey response rate was 31.3% (308/984). Significant positive predictors for reported publication rates of ≥20% were: involved individuals: research director/coordinator, individuals trained in statistics, non-pharmacy medical staff; requirements: Collaborative Institutional Training Initiative training, research seminars/training courses, research manuscript; learning experience structure: research committee; educational methods: didactic residency-led lectures/courses, formal workshops, self-taught online modules; and formal education: manuscript preparation. Conclusion: This study suggests there are differences in the research learning experiences at PGY1 Pharmacy residencies with reported resident publications rates of ≥20% vs <20%. We encourage PGY1 Pharmacy residency programs to consider implementing elements associated with reported resident publication rates of ≥20%., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It is unknown whether ChatGPT provides quality responses to infectious diseases (ID) pharmacotherapy questions. This study surveyed ID pharmacist subject matter experts (SMEs) to assess the quality of ChatGPT version 3.5 (GPT-3.5) responses., Methods: The primary outcome was the percentage of GPT-3.5 responses considered useful by SME rating. Secondary outcomes were SMEs' ratings of correctness, completeness, and safety. Rating definitions were based on literature review. One hundred ID pharmacotherapy questions were entered into GPT-3.5 without custom instructions or additional prompts, and responses were recorded. A 0-10 rating scale for correctness, completeness, and safety was developed and validated for interrater reliability. Continuous and categorical variables were assessed for interrater reliability via average measures intraclass correlation coefficient and Fleiss multirater kappa, respectively. SMEs' responses were compared by the Kruskal-Wallis test and chi-square test for continuous and categorical variables., Results: SMEs considered 41.8% of responses useful. Median (IQR) ratings for correctness, completeness, and safety were 7 (4-9), 5 (3-8), and 8 (4-10), respectively. The Fleiss multirater kappa for usefulness was 0.379 (95% CI, .317-.441) indicating fair agreement, and intraclass correlation coefficients were 0.820 (95% CI, .758-.870), 0.745 (95% CI, .656-.816), and 0.833 (95% CI, .775-.880) for correctness, completeness, and safety, indicating at least substantial agreement. No significant difference was observed among SME responses for percentage of responses considered useful., Conclusions: Fewer than 50% of GPT-3.5 responses were considered useful by SMEs. Responses were mostly considered correct and safe but were often incomplete, suggesting that GPT-3.5 responses may not replace an ID pharmacist's responses., Competing Interests: Potential conflicts of interest. J. M. S. served on an advisory board for Paratek Pharmaceuticals. E. B. C. served on an advisory board and speakers bureau for Seqirus. W. D. K. received research grants from Melinta, Merck & Co, and Shionogi, Inc and served on an advisory board for Theratechnologies, Inc. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Medical training can be a challenging time for residents both professionally and personally. Resident support programs must be able to address a range of potential experiences, be accessible and easy to navigate, and consider the unique context of residency. Rigorous evaluation of resident support programs is needed to determine whether these programs are meeting these goals., Methods: The Directors of Resident Support (DRS) program, launched in January 2021 at the Cumming School of Medicine at the University of Calgary, is a near-peer support model consisting of three faculty physicians, trained in peer support, who receive contacts from residents needing support for any issue. DRS physicians provide empathetic listening, referral to existing resources, and peer support for residents. A multisource evaluation of the DRS program, including field notes, data collection forms, and surveys, was guided by the Donabedian framework., Results: There were 62 total contacts in the 2-year evaluation period which required a median 2 h to address (range 5 min to more than 40 h). The most common topic for contact was to discuss feedback or evaluation (n = 10, 24.4%) and the most common response was listening and support (n = 29, 70.7%). Residents also contacted DRS to discuss experiences of racism, physical assault, sexual harassment, and mental health crises. Residents (n = 13) rated a median score of 74 out of possible 100 for usefulness (interquartile range [IQR] 1-100, with higher scores suggesting greater usefulness). Free text survey responses suggested that residents felt validated by contact with the program though some residents felt that additional follow-up would have been helpful., Conclusion: The DRS program has been well-utilized by residents for a variety of issues. Postgraduate Medical Education offices seeking to create resident support programs may anticipate that about 3% of residents may use a similar program per year and that the typical interaction would last 2 h, with a wide range. Feedback suggested that similar programs should have a formal process for follow-up with residents to ensure their concern was addressed and that resident supporters should have diverse lived experiences., (© 2024. The Author(s).)

Background: Cefazolin is guideline recommended for perioperative prophylaxis in orthopedic surgery. Despite its unique R1 side chain, cefazolin is often avoided in patients with beta-lactam allergy with concern for cross reactivity. Objectives: The primary outcome was the percentage of patients who received cefazolin perioperatively. Secondary outcomes included the percentage of patients with a beta-lactam allergy clarified following the telephone interview and clinical outcomes including acute kidney injury, surgical site infection, Clostridioides difficile infection, and re-admission at 30 and 90 days. Methods: This single-center, quasi-experimental study evaluated a pilot program in which a pharmacist phoned patients > 18 years of age with a scheduled orthopedic surgery and a documented beta-lactam allergy to assess their allergy preoperatively. Recommendations to use cefazolin were based on an algorithm. Patients were divided into pre- and post-intervention cohorts. Results: A total of 832 patients were screened for inclusion with 135 and 66 patients included in the pre- and post-intervention cohorts. No significant difference was identified in the primary outcome. In the post-intervention cohort, 62% had a beta-lactam reaction updated in the electronic medical record. Those with a beta-lactam allergy delabeled or made less severe were numerically more likely to receive cefazolin than those with an unchanged reaction or a reaction made more severe (95.2% vs 68% vs 65%). There were no differences in clinical outcomes between groups. Conclusion: A pharmacist-conducted preoperative beta-lactam allergy interview in adult patients undergoing elective orthopedic surgery improved beta-lactam allergy documentation but, did not result in increased utilization of cefazolin., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Wesley D. Kufel has received research grants from Merck and Co. and Melinta Therapeutics and served on the advisory board for Theratechnologies. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM)., Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging., Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up., Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM., Funding: The U.S. Food and Drug Administration., Competing Interests: SSJ, LGW, SA, JMS, HCW, JCM, JHS, RSB, VM, XJ, OHF, BF, SB, RCA, SAM, NM, JAS, SS, DV, AKVH, MJC, JK, SH, CM, MDC, MS, LN, JYA, SCU, PR, JKP, JGM, JAV, MPD, MB, PB, PE, KM, KG, MLD, KAA, AK, SBB, ALD, PKM, JS, ALC, JDR, ZP, AC, YS, LG, MA, MJ, JDR, NN, EDD report no competing interests. ASH: Site PI for the CAMP study—NHLBI funded, Site PI for MUSIC—NIH funded, Site PI for PREVAIL, supported by a sub-agreement from the Johns Hopkins University with funds provided by Grant No. R61HD105591 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the Office of the Director, National Institute of Health (OD). Scientific advisory board member of OP2 DRUGS (“OP2”), states that no work has been done. ABY: Institution received funds for conducting phase 3 clinical trials for Pfizer mRNA COVID-19 vaccine (C4591007 and C4591048). LEH: Patent US11457889B2, issued: Oct 4, 2022, Patent US2023/0016283A1 Published: Jan 19, 2023. JK: $530 Honorarium for speaking at Cleveland Clinic Valve Disease, Structural Interventions, and Diastology/Imaging Summit in 2/2023. FH: Payment for Expert Testimony in pending court case as an expert witness to discuss the risk of C-VAM. DT and SS: Grant or contract from New England Research Institute for participation in Pediatric Heart Network CAMP Study. MJC: Subject matter expert for CDC CISA program, Consulting fees Longerone Inc., (© 2024 The Author(s).)

Atrial function provides insight into ventricular diastolic function. Invasive assessment of left ventricular (LV) diastolic function correlates with development of sustained ventricular tachyarrhythmias in patients with repaired tetralogy of Fallot (rTOF). Non-invasive assessment of atrial function may prove key towards assessment of diastolic function. We longitudinally evaluated the progression of biatrial function in patients with rTOF, regardless of pulmonary valve replacement (PVR). Patients with rTOF who had multiple CMR were identified. CMR examinations were retrospectively reviewed. Left (LA) and right (RA) atrial size and function were measured in the two and four-chamber views and assessed over time and after PVR. Left and right atrial reservoir, conduit, pump strain and strain rates were determined using tissue tracking. Thirty-six patients with rTOF were identified (64% male), ten (28%) had PVR during the study. Median age of PVR was 16.5 years. No improvement in RA or LA function was observed after PVR. A decline in RA reservoir strain rate (p < 0.05) and RA pump strain (p < 0.05) were observed despite improvements in right ventricular systolic function (p < 0.05). In patients who had multiple CMR without PVR, RA reservoir strain rate (p < 0.05) and pump strain rate (p < 0.05) worsened over time. LA pump strain decreased over time in all patients. There is progressive decline of several RA functional parameters over time. No significant improvement in LA or RA function after PVR was observed. Additional studies are needed to understand how these changes may relate to poor outcomes and potentially better guide timing of PVR., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase., Design: This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31., Setting: The study was conducted in a 752-bed tertiary care, academic medical center., Intervention: Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults., Results: For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics., Conclusions: Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.

Background: The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection., Objective: We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB., Methods: This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation., Results: Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively., Conclusions and Relevance: D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Wesley D. Kufel has received research grants from Merck and Melinta and has served on the advisory board for Theratechnologies, Inc. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other authors have nothing to disclose.

Background: The risk of linezolid-associated serotonin toxicity remains unclear. This study sought to evaluate the incidence of serotonin toxicity among hospitalized patients who received linezolid with or without concurrent serotonergic agents (SAs). Secondary outcomes were to assess the dose, agent selection and number of SAs., Methods: A single-centre, retrospective cohort study of hospitalized patients aged ≥18 years who received at least one dose of linezolid with or without SAs between 1 January 2014 and 30 June 2021 was performed. Patients were excluded if they were aged <18 years, had linezolid ordered but not administered, were pregnant or were incarcerated. Up to five concurrent SAs were assessed, and dose category was classed as low, moderate or high (dose <33%, 33-66% or >66% of maximum daily dose, respectively). Serotonin toxicity was identified by searching patients' electronic medical records. If identified, the Sternbach criteria and Hunter criteria were applied., Results: Of 2022 patients screened, 1743 were included in this study. Mean age, weight and linezolid duration were 58.5 years, 90.7 kg and 3.8 days, respectively. Approximately 67% (1168/1743) of patients received linezolid with at least one SA, and several patients received multiple SAs. Most patients (53.8%; 616/1144) received moderate- and/or high-dose SAs. Only two patients (0.11%) were identified as possible cases of serotonin toxicity based on the electronic medical record search. However, the incidence of serotonin toxicity was 0.06% (1/1743) based on the Sternbach criteria and 0% (0/1743) based on the Hunter criteria., Conclusions: Serotonin toxicity among hospitalized patients who received linezolid with or without SAs was exceedingly rare, even among those who received multiple and high-dose SAs., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited., Objective: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs., Methods: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel., Results: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%., Conclusions: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Background: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described., Objective: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use., Methods: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale., Results: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use., Conclusion and Relevance: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

We present a case of a newborn with a rare presentation of obstructed supracardiac total anomalous pulmonary venous connection who required emergent cannulation to extracorporeal membrane oxygenation (ECMO). Computed tomographic angiography of the heart was performed and using novel virtual dissection techniques aided in surgical planning and guidance. Computed tomographic angiography can be successfully performed in neonates with complex congenital heart disease on ECMO without adjustment of flows to aid in surgical management and novel virtual dissection techniques aid in complex anatomical delineation and spatial orientation with noncardiac structures. The preoperative imaging in this case allowed for appropriate and detailed presurgical planning and contributed to the excellent outcome of this patient.

Background: Compliance with guideline recommendations for surgical antibiotic prophylaxis (SAP) in colorectal surgery, particularly redosing, has been suboptimal at many institutions including ours. This study aimed to evaluate if single-dose antibiotic prophylaxis with ertapenem improves compliance with guideline recommendations for SAP versus multiple-dose antibiotic prophylaxis in elective colorectal surgery. Methods: A retrospective, cohort study of the use of ertapenem compared with standard of care antibiotic agents was performed in adult patients undergoing elective colorectal surgery at an academic medical center between January 2020 and February 2022. The primary outcome was compliance with guideline-recommended SAP for colorectal surgery. The secondary outcome was surgical site infections (SSIs) within 30 days after surgery. Results: A total of 135 patients were included in this study. Fifty-eight patients received single-dose antibiotic prophylaxis with ertapenem and 77 patients received multiple-dose antibiotic prophylaxis. Cefazolin plus metronidazole was the most common multiple-dose regimen (65 of 77). Single-dose antibiotic prophylaxis with ertapenem increased overall SAP compliance (96.6% vs. 64.9%; p < 0.001) as well as compliance with antibiotic administration within the recommended time period before incision (96.6% vs. 84.4%; p = 0.022), compliance with intra-operative antibiotic redosing when warranted (100% vs. 83.1%; p < 0.001), and compliance with guideline-recommended dosing (100% vs. 92.2%; p = 0.037). Surgical site infection rates were not statistically different between the groups (12.1% vs. 19.4%; p = 0.248). Conclusions: Single-dose antibiotic prophylaxis with ertapenem increased compliance with guideline-recommended SAP for elective colorectal surgeries. No statistically significant difference was observed in SSI rates regardless of the antibiotic regimen used.

Study Objective: The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post-ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day readmission for MRSAB, 90-day all-cause mortality, MRSAB-related mortality, and incidence of antibiotic-associated adverse effects., Design: Single-center, retrospective cohort study between January 1, 2016, and December 31, 2021., Setting: State University of New York Upstate University Hospital, a 748-bed tertiary care, academic medical center in Syracuse, NY., Patients: Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti-MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated., Measurements and Main Results: Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin-associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline-associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post-ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90-day readmission for MRSAB. 90-day all-cause mortality and MRSAB-related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively., Conclusions: Vancomycin plus ceftaroline may represent an effective and well-tolerated salvage regimen option for persistent MRSAB., (© 2022 Pharmacotherapy Publications, Inc.)

Background: To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use., Objectives: To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2 g IV q6h (regimen 1) and 2 g IV q8h (regimen 2)] during treatment of CRAB meningitis., Patients and Methods: A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course., Results: CSF AUC was 146.49 and 118.28 mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF/AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed., Conclusions: Cefiderocol, when given as 2 g q8h and 2 g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4 mg/L) for 100% of the dosing interval., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting, and limited data describe AS interventions at hospital discharge. Acknowledging the potential value of discharge AS, we used our existing resources to review discharge oral antimicrobial prescriptions., Objective: The primary objective of this retrospective, single-center study was to evaluate the impact of an AS program on discharge oral antimicrobial prescriptions., Methods: Discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious diseases (ID) pharmacist, and recorded into our data collection tool from September 1, 2020, to February 28, 2021, were evaluated retrospectively. The primary outcome was to identify the frequency a drug-related problem (DRP) was identified by an ID pharmacist. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted., Results: Of the 803 discharge oral antimicrobial prescriptions reviewed, at least 1 DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. At least 1 intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). The most common types of interventions included recommendations for a different duration, a different dose or frequency, and antimicrobial discontinuation. When interventions to reduce treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5-10) days to 4 (0-5.5) days ( P < 0.001)., Conclusion and Relevance: An ID pharmacist's review of discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.

Purpose: While some guidelines recognize the need for β-lactam therapeutic drug monitoring (TDM), there is still a paucity of data regarding the prevalence of and barriers to performing β-lactam TDM in the United States. We sought to estimate the prevalence of β-lactam TDM, describe monitoring practices, and identify actual and perceived barriers to implementation among health systems in the US., Methods: A multicenter, cross-sectional, 40-item electronic survey was distributed to all postgraduate year 2 (PGY2) infectious diseases (ID) pharmacy residency program directors (RPDs) listed in the American Society of Health-System Pharmacists pharmacy residency directory. The primary outcome was the percentage of institutions with established β-lactam TDM. Secondary outcomes included assessing β-lactam TDM methods and identifying potential barriers to implementation., Results: The survey was distributed to 126 PGY2 ID RPDs, with a response rate of 31.7% (40 of 126). Only 8% of respondents (3 of 39) performed β-lactam TDM. Patient populations, therapeutic targets, and frequency and timing of obtaining repeat β-lactam concentration measurements varied among institutions. The greatest barrier to implementation was lack of access to testing with a rapid turnaround time. Institutions were unlikely to implement β-lactam TDM within the next year but were significantly more inclined to do so within 5 years (P < 0.001)., Conclusion: β-lactam TDM was infrequently performed at the surveyed US health systems. Lack of access to serum concentration testing with rapid turnaround and lack of US-specific guidelines appear to be considerable barriers to implementing β-lactam TDM. Among institutions that have implemented β-lactam TDM, there is considerable variation in monitoring approaches., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort., Methods and Results: Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0-13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19-47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87-23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18-21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction., Conclusion: No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage., Clinical Trial Registration: The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered., (© 2021. The Author(s).)

Objective: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB)., Methods: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures., Results: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed., Conclusions: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes., Competing Interests: Declaration of competing interest Wesley D. Kufel has received research grants from Merck and Melinta Therapeutics, and served on the advisory board for Theratechnologies, Inc. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other others have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: In this study, we aimed to characterize the clinical presentation, short-term prognosis, and myocardial tissue changes as noted on cardiovascular magnetic resonance (CMR) or cardiac MRI in pediatric patients with coronavirus disease 2019 vaccination-associated myocarditis (C-VAM)., Methods: In this retrospective multicenter study across 16 US hospitals, patients <21 years of age with a diagnosis of C-VAM were included and compared with a cohort with multisystem inflammatory syndrome in children. Younger children with C-VAM were compared with older adolescents., Results: Sixty-three patients with a mean age of 15.6 years were included; 92% were male. All had received a messenger RNA vaccine and, except for one, presented after the second dose. Four patients had significant dysrhythmia; 14% had mild left ventricular dysfunction on echocardiography, which resolved on discharge; 88% met the diagnostic CMR Lake Louise criteria for myocarditis. Myocardial injury as evidenced by late gadolinium enhancement on CMR was more prevalent in comparison with multisystem inflammatory syndrome in children. None of the patients required inotropic, mechanical, or circulatory support. There were no deaths. Follow-up data obtained in 86% of patients at a mean of 35 days revealed resolution of symptoms, arrhythmias, and ventricular dysfunction., Conclusions: Clinical characteristics and early outcomes are similar between the different pediatric age groups in C-VAM. The hospital course is mild, with quick clinical recovery and excellent short-term outcomes. Myocardial injury and edema are noted on CMR. Close follow-up and further studies are needed to understand the long-term implications and mechanism of these myocardial tissue changes., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose of Review: Significant improvements in the diagnosis and management of patients with congenital heart disease (CHD) have led to improved survival. These patients require life-long noninvasive evaluation. The use of advanced imaging such as cardiac magnetic resonance imaging (CMR) and cardiac computed tomography (CCT) has increased to support this need. The purpose of this review is to discuss the basics of advanced cardiac imaging, indications and review the recent innovations., Recent Findings: Recent literature has demonstrated the increasing reliance of advanced imaging for CHD patients. In addition, research is focusing on CMR techniques to shorten scan time and address previous limitations that made imaging younger and sicker patients more challenging. CCT research has involved demonstrating high-quality images with low radiation exposure. Advances in digital technology have impacted the interactivity of 3D imaging through the use of virtual and augmented reality platforms. With the increased reliance of advanced imaging, appropriate use criteria have been developed to address possible under or over utilization., Summary: The utilization of advanced cardiac imaging continues to increase. As CMR and CCT continue to grow, increased knowledge of these modalities and their usage will be necessary for clinicians caring for CHD patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cefiderocol is a novel siderophore cephalosporin that forms a complex with extracellular free ferric iron, which leads to transportation across the outer cell membrane to exert its bactericidal activity through cell wall synthesis inhibition. This pharmacological property has rendered cefiderocol active against several clinically relevant MDR Gram-negative bacteria as evidenced by several in vitro and in vivo studies. Cefiderocol was first approved by the US FDA on 14 November 2019 for the treatment of complicated urinary tract infections. On 28 September 2020, cefiderocol was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The FDA-approved indications are based on clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In APEKS-cUTI, cefiderocol demonstrated non-inferiority to imipenem/cilastatin for the treatment of complicated urinary tract infection caused by MDR Gram-negative bacteria. In APEKS-NP, cefiderocol demonstrated non-inferiority to meropenem for treatment of nosocomial pneumonia. However, in CREDIBLE-CR, higher all-cause mortality was observed with cefiderocol compared with best available therapy for the treatment of severe infections caused by Gram-negative bacteria, primarily in the subset of patients with Acinetobacter spp. infections. Several case reports/series have demonstrated clinical success with cefiderocol for a variety of severe infections. The purpose of this article is to review available data on the mechanism of action, in vitro and in vivo data, pharmacokinetics, pharmacodynamics, susceptibility testing, efficacy and safety of cefiderocol to address its role in therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Adults with obesity and type 2 diabetes mellitus (T2DM) related to obesity are at increased risk of heart failure with preserved ejection fraction (HFpEF). Whether left ventricular (LV) diastolic function abnormalities related to obesity and T2DM start in adolescence and early adulthood is unknown. We non-invasively evaluated the differences seen in LV diastolic and left atrial (LA) function in adolescents and young adults with obesity and T2DM., Methods: We analyzed echocardiographic measures of LV diastolic function in patients with structurally normal hearts which were divided into 3 groups (normal weight, obese, and T2DM). Spectral and tissue Doppler and 2-D speckle tracking measurements of diastolic function were obtained. Logistic regression was performed to compare the prevalence of abnormalities in diastolic function based on the worst 25th percentile for each measure to determine the prevalence of diastolic and LA function abnormalities in obese and T2DM patients., Results: 331 teenagers and young adults (median age 22.1 years) were analyzed (101 normal weight, 114 obese, 116 T2DM). Obese and T2DM group had lower E/A and higher E/e'. Obese and T2DM patients had significantly lower atrial reservoir, conduit, and booster strain and worse reservoir and conduit strain rate compared to normal patients (p < 0.001 for all measures). All patients had normal LA volumes. On multivariable analysis, conduit strain and reservoir and conduit strain rate were independently associated with having below the 25th percentile e'. Conduit strain rate was independently associated with having below the 25th percentile for mitral E/A ratio on multivariable analysis., Conclusions: Abnormal indices of LV diastolic function are detected in adolescents and young adults with obesity and T2DM. LA function and strain analysis were able to detect evidence of decreased reservoir, conduit, and booster strain in these patients although LA volume was normal. The use of LA function strain may increase our ability to detect early diastolic function abnormalities in this population.

Objectives: It is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)-based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC-based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC- or trough-based monitoring., Design: This was a single-center, retrospective cohort study., Setting and Participants: This study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC-based monitoring at our institution., Outcome Measures: The primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay., Results: A total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07-$601.05) for the AUC:MIC-based group compared with $316.79 ($253.36-$520.96) for the trough-based group (P = 0.687)., Conclusion: Vancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Cefiderocol is a novel siderophore cephalosporin antibacterial with activity against carbapenem-resistant Gram-negative bacteria including Pseudomonas aeruginosa . We report a medically complex patient treated with compassionate use cefiderocol for an empyema caused by extensively drug-resistant P. aeruginosa as well as clinical considerations for cefiderocol use based on our findings. We observed a potential discordance in cefiderocol susceptibility testing results depending if disk diffusion or iron-depleted cation-adjusted Mueller Hinton Broth dilution is used. Furthermore, interpretative criteria differ between the Clinical Laboratory Standards Institute and United States Food and Drug Administration for P. aeruginosa , which makes cefiderocol interpretation potentially challenging for clinicians. We may have also observed selective pressure from prior cefiderocol exposure given the respective increases and decreases in MIC values and zone diameters for P. aeruginosa isolates following cefiderocol treatment. Additional data are needed to further describe cefiderocol use, susceptibility testing, and resistance development as real-world clinical use expands., Competing Interests: W.D.K. has received grant funding from Melinta and Merck and has served on the advisory board for Theratechnologies, Inc. J.M.S has served on the advisory board for Paratek Pharmaceuticals. All other authors have nothing to disclose., (© 2020 The Authors.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Objective: To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C-I) or intermittent infusion (I-I) vancomycin in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics., Design: Single-center propensity score-matched retrospective cohort study., Setting: OPAT clinic affiliated with two nearby hospitals., Patients: We identified 300 patients who received C-I or I-I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups., Measurements and Main Results: After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22-fold decrease in nephrotoxicity risk (C-I 6.8% [5/74 patients] vs I-I 18.9% [14/74 patients]; odds ratio 3.22, 95% confidence interval 1.10-9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I-I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C-I and I-I groups (13.5% [10/74 patients] vs 23.0% [17/74 patients], p=0.147)., Conclusion: In an OPAT setting, C-I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I-I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C-I versus I-I vancomycin., (© 2020 Pharmacotherapy Publications, Inc.)

Diastolic dysfunction has correlated with adverse outcomes in various forms of unrepaired and repaired or palliated congenital heart disease (CHD). The non-invasive assessment of diastolic function in pediatric and adult patients with CHD remains challenging. Atrial size has a pivotal role in the evaluation of diastolic function; however, a growing body of evidence supports the additional role of atrial function as a more sensitive parameter of ventricular diastolic dysfunction. While the importance of atrial function is becoming clearer in adult acquired heart disease, it remains ambiguous in those with CHD. In this review we set the stage with the current understanding of diastolic function assessment in CHD, followed by insight into atrial form and function including its non-invasive assessment, and conclude with the current knowledge of atrial function in CHD. A general pattern of decrease in reservoir and conduit function with compensatory increase followed by decompensatory decrease in contractile function seems to be the common pathway of atrial dysfunction in most forms of CHD.

Objective: Deciding on a surgical pathway for neonates with ≥2 left heart obstructive lesions is complex. Predictors of the successful biventricular (2V) repair in these patients are poorly defined. The goal of our study was to identify patients who underwent the 2V repair and assess anatomic and echocardiographic predictors of success., Design: Infants born between July 2015 and August 2017 with ≥2 left heart obstructive lesions with no prior interventions were identified (n = 19). Patients with aortic or mitral valve (MV) atresia and critical aortic stenosis were excluded. Initial echocardiograms were reviewed for aortic, MV, tricuspid valve annulus size, and left (LV) and right (RV) ventricle diastolic longitudinal dimensions. The valve morphology and presence of a ventricular septal defect (VSD) and coarctation were assessed. Clinical outcomes included successful 2V repair, complications, and repeat interventions or surgeries. Failed 2V repair was defined as a takedown to single ventricle (1V) physiology, cardiac transplantation, or death., Results: For 2V repair, 14/19 patients were selected and for 1V, 5/19 patients were selected. Initial surgical procedures of the 2V group were simple coarctation repair (5), complex coarctation/arch reconstruction +/- septal defect closure (6), hybrid stage 1 (2), and none (1). Three of the 2V patients required reintervention in the first 90 days. The LV to RV diastolic longitudinal ratio >0.75 and mitral/tricuspid ratio of <0.8 were observed in 13/14 of the 2V patients. The LV:RV ratio and the aortic valve z score were significantly larger in the 2V group compared to the 1V group. All patients in the 1V group had a nonapex forming LV. There was no mortality with follow-up to three years of age., Conclusions: This study showed excellent short-term and midterm surgical results in the 2V population. The LV:RV diastolic longitudinal ratio may be a useful tool in the risk stratification of a successful 2V repair even in cases with a small MV., (© 2019 Wiley Periodicals, Inc.)

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution., Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L., Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107)., Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Objectives: To determine the prevalence, age of onset, and risk factors for overweight and obesity in children with congenital heart disease (CHD)., Study Design: Children with CHD who were seen at our institution from 1996 to 2017 were studied. Patients were full-time residents of the United States and were receiving all cardiac care at our institution. Patients were categorized by age and CHD diagnosis. The date of last normal weight for age and the date of first recorded weight in the range of overweight and obese were documented., Results: Nine hundred sixty-eight patients with CHD were included. The prevalence of overweight and obesity was 31.5% and 16.4%, respectively. For patients who became overweight or obese, the last recorded normal weight was between 6 and 10 years of age. Electrophysiologic disease and older age were risk factors for obesity., Conclusions: Children with CHD have an increasing risk of becoming overweight and obese in early childhood. This study provides important information and identifies critical period to implement preventative measures and counsel families about the risk of obesity in CHD., (© 2019 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to (1) determine whether academic medical centers implemented area under the concentration-time curve (AUC)-based monitoring for vancomycin and (2) characterize perceived barriers to implementation and challenges experienced during the implementation process., Methods: A multicenter, cross-sectional electronic survey was distributed to pharmacy representatives from 124 academic medical centers within the Vizient University Health System Consortium Pharmacy Network., Results: Seventy-eight institutions completed the survey, representing a 62.9% response rate. Most institutions were approximately 500-1,000 beds (68/78, 87.2%), and pharmacists were primarily responsible for vancomycin therapeutic drug monitoring (66/78, 84.6%) using pharmacist-driven protocols (57/78, 73.1%). Less than one fourth (18/78, 23.1%) of responding academic medical centers performed AUC-based vancomycin monitoring, and the majority (12/18, 66.7%) used 2-point pharmacokinetics, with a smaller fraction using either Bayesian software or population-based pharmacokinetics. Of the responding institutions that only perform trough-based therapeutic drug monitoring (60/78, 76.9%), most (53/60, 88.3%) did not plan to or were unsure about transitioning to AUC-based monitoring within the next year. Both the most common challenge encountered (13/18, 72.2%) for institutions performing AUC-based monitoring and the most common barrier (44/60, 73.3%) to implementation of this monitoring strategy were pharmacist and/or provider unfamiliarity., Conclusion: The majority of surveyed academic medical centers have not yet implemented AUC-based vancomycin monitoring, and most institutions did not plan to adopt or were unsure about adopting this monitoring strategy within the next year., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The United States has seen an increased consumption of carbapenem antibiotics in recent years. The increased utilization of these agents has potential negative consequences, including the increasing incidence of carbapenem-resistant Enterobacteriaceae. Reasons for the rise in carbapenem use among providers in acute care hospitals are not well elucidated in literature. The objectives of this study were to identify factors that influence empiric carbapenem use among providers in a single academic medical center, and to assess therapeutic knowledge pertaining to carbapenem use. Methods: A cross-sectional, single-center, 9-item electronic research survey was developed independently and validated by an infectious diseases pharmacist and infectious diseases physician. The survey was distributed to email accounts of providers at a single academic medical center. Demographic data, factors affecting carbapenem prescription, and baseline therapeutic knowledge were assessed. Results: Ninety-five of 416 providers responded to the survey (response rate of 22.8%). Respondents were well distributed across all levels of training with primary roles in internal medicine and surgery. The most important factors influencing empiric carbapenem use were suspected pathogens at the site of infection, drug allergies, history of multidrug resistant organisms, severity of illness, type of infection, and local resistance rates. A recommendation from a pharmacist was selected as the most likely factor for deterring carbapenem use. Misconceptions pertaining to penicillin drug allergy and beta-lactam cross reactivity, knowledge of local resistance rates according to the institutional antibiogram, and comparative efficacy data for carbapenems were apparent across all levels of training. Conclusions: Provider misconceptions regarding several factors appear to contribute to unnecessary use of carbapenems. An opportunity exists for hospital pharmacists to improve the prescribing patterns of carbapenems by correcting provider misconceptions through education., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D  in vitro models for studying the physiology and physiopathology of the central nervous system.

Pediatric chest pain is a common reason for cardiology referral, and evaluation of exertional chest pain requires proper delineation of coronary anatomy. Congenital coronary anomalies are rare and often benign. However, certain anomalies such as intramural coronary arteries and myocardial bridges have been associated with angina, ventricular arrhythmias, and sudden cardiac death. We present a case of a 10-year-old male with exertional chest pain whose coronary anatomy could not be defined by echocardiography and further evaluation by computed tomography angiography revealed a rare congenital coronary anomaly.

Limited evidence exists evaluating pharmacokinetic thresholds for vancomycin efficacy and nephrotoxicity using non-Bayesian methods. The objective of this study was to evaluate the 24-h steady-state vancomycin area under the concentration-time curve (AUC 24 ) thresholds for efficacy and nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSA-B) after implementing two-point pharmacokinetic therapeutic drug monitoring. A single-centre, retrospective cohort study was performed including adult patients admitted between 1 June 2016 and 1 January 2018 with MRSA-B treated with vancomycin for ≥72 h. The AUC 24 was calculated using peak and trough vancomycin serum concentrations. Clinical success was defined as defervescence and blood culture sterilisation by Day 7. Nephrotoxicity was defined as an increase in serum creatinine of >0.5 mg/dL (or ≥50%) from baseline. Classification and regression tree (CART) analyses were performed to identify AUC 24 thresholds for efficacy and nephrotoxicity. Forty-six patients were included in the study. Clinical success and nephrotoxicity were observed in 81.8% and 13.0%, respectively. The CART-derived vancomycin AUC 24 thresholds for clinical success and nephrotoxicity were ≥297 mg·h/L and ≥710 mg·h/L, respectively. Patients with an AUC 24 ≥297 mg·h/L had a >2.7-fold increase in clinical success compared with those who did not (89.5% vs. 33.3%, respectively; P = 0.01), and patients with an AUC 24 ≥710 mg·h/L had a >7-fold increase in nephrotoxicity compared with those with an AUC 24 <710 mg·h/L (66.7% vs. 9.3%, respectively; P = 0.04). This study supports current recommendations to target vancomycin AUC 24 values of 400-600 mg·h/L when calculated using two-point pharmacokinetics, although a wider range may exist., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Delafloxacin is a novel anionic fluoroquinolone (FQ) approved for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by a number of Gram-positive and Gram-negative organisms including MRSA and Pseudomonas aeruginosa. The unique chemical structure of delafloxacin renders it a weak acid and results in increased potency in acidic environments. In Phase III studies, delafloxacin had similar outcomes to comparator regimens for treatment of ABSSSIs, and was well tolerated overall. Similar to other FQs, delafloxacin is available in both intravenous and oral formulations, but differs in that delafloxacin exerts a minimal effect on cytochrome P450 enzymes and on the corrected QT interval. This novel FQ has the potential to be utilized across a wide variety of clinical settings; however, post-marketing surveillance and long-term safety and resistance data will be essential to identify optimal use scenarios.

What Is Known and Objective: Limited evidence describes dalbavancin use in infective endocarditis (IE)., Case Description: A 27-year-old pregnant female received 4 weeks of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and tricuspid valve IE after conventional therapy was no longer an option due to non-compliance. Despite having a smaller cardiac vegetation following dalbavancin, she was bacteraemic <2 weeks later with vancomycin-intermediate (VISA) and telavancin-non-susceptible S. aureus., What Is New and Conclusion: This is the first report of unsuccessful IE treatment with dalbavancin. Blood cultures grew VISA and lipoglycopeptide-non-susceptible S. aureus <2 weeks following dalbavancin. Both outcomes raise concerns about using dalbavancin for IE., (© 2017 John Wiley & Sons Ltd.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been associated with serious urinary tract infections (UTIs) including pyelonephritis and urosepsis. The Food and Drug Administration (FDA) issued a label change to include this warning in December 2015 due to a small number of cases (n = 19) reported to the FDA Adverse Event Reporting System. Details of these cases are limited and none involved empagliflozin. To date, there has been no published literature comprehensively describing serious UTIs attributed to empagliflozin. We describe a case of septic shock due to Serratia marcescens pyelonephritis and bacteremia that required intensive care unit admission in a well-controlled, type 2 diabetic patient who had begun taking empagliflozin 2 months prior. The patient was treated successfully with intravenous antibiotics followed by oral ciprofloxacin. After discontinuation of empagliflozin and completion of antibiotic therapy, no subsequent UTIs were documented in the following 4 months.