Characterization of initial CLABSI culture results to support antimicrobial de-escalation in pediatric GI inpatients.

OBJECTIVES: Central Line-associated Bloodstream Infections (CLABSIs) pose a serious mortality and morbidity risk. An institutional protocol was developed for the evaluation and empirical antibiotic treatment of possible CLABSIs. The potential impact of de-escalating antimicrobial therapy based on initial Gram stain and molecular identification was assessed. METHODS: All positive blood cultures from patients admitted to the gastroenterology service at a large pediatric medical center were collected from 1/1/14 to 12/31/20. Cultures that were negative, repeated, or causative organisms that were unable to be identified with susceptibility data were excluded. Timepoints and organism(s) from each culture were recorded. Polymicrobial cultures were classified as containing only gram-positive organisms (polymicrobial GP), only gram-negative organisms (polymicrobial GN), or mixed spectrum. RESULTS: During the 6-year period, 361 positive blood cultures were included in the study. Single isolates were identified in 79.5% (287/361) of cultures. Polymicrobial cultures from confirmed central line source accounted for 15.0% (54/361), with 6.4% (23/361) Polymicrobial GP, 4.4% (16/361) Polymicrobial GN, and 4.2% (15/361) being mixed-spectrum cultures. Both organism types were detected on initial gram-stain in 40% (6/15) of the mixed-spectrum cultures, another 26.7% (4/15) had the opposite-spectrum organism identified within an average of <3 h and the remaining 33.3% (5/15) had the opposite-spectrum organism identified by culture growth. CONCLUSIONS: Polymicrobial mixed-spectrum cultures accounted for <5% of positive blood cultures and most isolates were identified within 3 h of first positivity. This may allow for further investigation of early de-escalation of therapy for this population and limit antimicrobial exposure.

Pharmacokinetics of Levetiracetam Seizure Prophylaxis in Severe Traumatic Brain Injury.

BACKGROUND: Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown. OBJECTIVE: This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis. METHODS: This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center. Patients with sTBI receiving seizure prophylaxis with LEV8 or LEV12 were eligible for enrollment. Five sequential, steady-state, postdose serum levetiracetam concentrations were obtained. Non-compartmental analysis (NCA) and compartmental approaches were employed for estimating pharmacokinetic parameters and projecting steady-state trough concentrations. Pharmacokinetic parameters were compared between LEV8 and LEV12 patients. Monte Carlo simulations (MCS) were performed to determine probability of target trough attainment (PTA) of 6 to 20 mg/L. A secondary analysis evaluated PTA for weight-tiered levetiracetam dosing. RESULTS: Ten male patients (5 LEV8; 5 LEV12) were included. The NCA-based systemic clearance and elimination half-life were 5.3 ± 1.2 L/h and 4.8 ± 0.64 hours. A one-compartment model provided a higher steady-state trough concentration for the LEV8 group compared with the LEV12 group (13.7 ± 4.3 mg/L vs 6.3 ± 1.7 mg/L; P = 0.008). Monte Carlo simulations predicted regimens of 500 mg every 6 hours, 1000 mg every 8 hours, and 2000 mg every 12 hours achieved therapeutic target attainment. Weight-tiered dosing regimens achieved therapeutic target attainment using a 75 kg breakpoint. CONCLUSION AND RELEVANCE: Neurocritically ill patients exhibit rapid levetiracetam clearance resulting in a short elimination half-life. Findings of this study suggest regimens of levetiracetam 500 mg every 6 hours, 1000 mg every 8 hours, or 2000 mg every 12 hours may be required for optimal therapeutic target attainment. Patient weight of 75 kg may serve as a breakpoint for weight-guided dosing to optimize levetiracetam therapeutic target attainment for seizure prophylaxis.

Aligning Provider Prescribing With Guidelines for Soft Tissue Infections.

OBJECTIVE: Despite evidence-based guidelines, antibiotics prescribed for uncomplicated skin and soft tissue infections can involve inappropriate microbial coverage. Our aim was to evaluate the appropriateness of antibiotic prescribing practices for mild nonpurulent cellulitis in a pediatric tertiary academic medical center over a 1-year period. METHODS: Eligible patients treated in the emergency department or urgent care settings for mild nonpurulent cellulitis from January 2017 to December 2017 were identified by an International Classification of Diseases, Tenth Revision, code for cellulitis. The primary outcome was appropriateness of prescribed antibiotics as delineated by adherence with the Infectious Diseases Society of America guidelines. Secondary outcomes include reutilization rate as defined by revisit to the emergency department/urgent cares within 14 days of the initial encounter. RESULTS: A total of 967 encounters were evaluated with 60.0% overall having guideline-adherent care. Common reasons for nonadherence included inappropriate coverage of MRSA with clindamycin (n = 217, 56.1%) and single-agent coverage with sulfamethoxazole-trimethoprim (n = 129, 33.3%). There were 29 revisits within 14 days of initial patient encounters or a reutilization rate of 3.0%, which was not significantly associated with the Infectious Diseases Society of America adherence. CONCLUSIONS: Our data show antibiotic prescription for nonpurulent cellulitis as a potential area of standardization and optimization of care at our center.

Cefepime Population Pharmacokinetics and Target Attainment in Critically Ill Patients on Continuous Renal Replacement Therapy.

Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT), which will affect their antimicrobial exposure. We aimed to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. Patients who were ≥18 years old, were admitted to the ICU, and received cefepime 2 g every 8 h as a 4-h infusion while on CRRT were enrolled prospectively. Samples were collected from the predialyzer ports, postdialyzer ports, and effluent fluid at 1, 2, 3, 4, and 8 h after the first dose and at steady state. Age, sex, weight, urine output, and CRRT parameters were recorded. Pmetrics was used for population PK and simulations. The target exposure was 100% of the dosing interval during which the free beta-lactam concentration is above the MIC (fT>MIC). Ten patients were included; their mean age was 53 years, and mean weight was 119 kg. Seventy percent were males. Cefepime was described by a five-compartment model. The downtime was applied to the CRRT flow rates, which were used to describe the rates of transfer between the compartments. At MICs of ≤8 mg/liter, intermittent infusion of 2 g cefepime every 8 h achieved good target attainment both early in therapy and at steady state. Only extended- and continuous-infusion regimens achieved good target attainment at MICs of 16 mg/liter. In conclusion, 2 g cefepime infused over 30 min followed by extended infusion of 2 g every 8 h achieved good target attainment at MICs of ≤16 mg/liter with different CRRT flow rates and may be considered in resistant bacterial infections.

Predicting Oral Beta-lactam susceptibilities against Streptococcus pneumoniae.

BACKGROUND: Oral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory concentration (MIC) testing. Currently, Clinical and Laboratory Standards Institute provides comments to use penicillin MIC ≤0.06 to predict oral cephalosporin susceptibility. However, no guidance is provided when cefotaxime MIC is known, leading to uncertainty with interpretation. The purpose of this study was to evaluate cefotaxime and penicillin MICs and their respective correlation to oral beta-lactam categorical susceptibility patterns. METHODS: 249 S. pneumoniae isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF) and then tested by broth microdilution method to penicillin, cefotaxime, amoxicillin, cefdinir, cefpodoxime, and cefuroxime. RESULTS: Using Clinical and Laboratory Standards Institute (CLSI) non-meningitis breakpoints for cefotaxime, 240/249 isolates were classified as susceptible. Of the cefotaxime susceptible isolates, 23% of the isolates are misrepresented as cefdinir susceptible. Amoxicillin correlated well with penicillin MIC breakpoints with only 1 discordant isolate out of 249. CONCLUSION: The correlation between amoxicillin and penicillin creates a very reliable predictor to determine categorical susceptibility. However oral cephalosporins were not well predicted by either penicillin or cefotaxime leading to the possible risk of treatment failures. Caution should be used when transitioning to oral cephalosporins in cefotaxime susceptible isolates, especially with higher cefotaxime MICs.

Variability in Antibiotic Use Across PICUs.

OBJECTIVES: To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. DESIGN: Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. SETTING: Forty-one freestanding children's hospital. SUBJECTS: Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. INTERVENTIONS: To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. RESULTS: The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared by all 41 PICUs. CONCLUSIONS: The wide variation in antibiotic use observed across children's hospital PICUs suggests inappropriate antibiotic use.

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream.

Home Insulin Pump Use in Hospitalized Children With Type 1 Diabetes.

Importance: Pediatric data on inpatient home insulin pumps are absent in the literature. Understanding safety of home insulin pumps, managed by patients or caregivers, during times of illness will help diabetes technology securely move into pediatric hospitals. Objective: To examine whether insulin can be safely and accurately delivered to hospitalized children through home insulin pumps when managed by patients or caregivers. Design, Setting, and Participants: This single-center, retrospective, observational cohort study included children with insulin-dependent diabetes admitted to a tertiary children's hospital from January 1, 2016, to December 31, 2021. In all these patients, diabetes was the primary or secondary diagnosis on admission. Exposure: Insulin delivery via home insulin pump, hospital insulin pump, or subcutaneous injection. Main Outcomes and Measures: Hyperglycemia (glucose, >250 mg/dL) and hypoglycemia (glucose, <45 mg/dL) rates (quantified as the proportion of total insulin-days), glucose variability, and diabetic ketoacidosis (DKA) recurrences were compared for hospital pumps (manual mode), home pumps (manual mode), and subcutaneous injections using bivariate tests. Results: There were 18 096 insulin-days among 2738 patients aged 0.5 to 25 years (median age, 15.8 years [IQR, 12.3-18.3 years]). Overall, 990 (5.5%) of insulin-days involved hospital insulin pumps, and 775 (4.3%) involved home pumps. A total of 155 insulin-days (15.7%) involving hospital pumps were hyperglycemic, compared with 209 (27.0%) involving home pumps and 7374 (45.2%) involving injections (P < .001). Moderate hypoglycemia days comprised 31 insulin-days (3.1%) involving hospital pumps compared with 35 (4.5%) involving home pumps and 830 (5.1%) involving injections (P = .02). Severe hypoglycemia did not differ significantly according to insulin delivery method. Two patients using injections (0.01%) developed DKA; no patients using hospital or home pumps developed DKA. Conclusions and Relevance: In this cohort study, home insulin pump use was found to be safe in a children's hospital regarding hyperglycemia and hypoglycemia. These data support use of home insulin pumps during pediatric admissions in patients who do not require intensive care and without active DKA.

Population pharmacokinetics of sirolimus in pediatric patients with neurofibromatosis type 1.

PURPOSE: The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex. METHODS: Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses. RESULTS: Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively). CONCLUSIONS: Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.

Beta-Lactam Allergy Association with Surgical Site Infections in Pediatric Procedures: A Matched Cohort Study.

BACKGROUND: Little is known about surgical site infection (SSI) risk among pediatric patients with reported beta-lactam allergy (BLA). METHODS: We performed a retrospective cohort study at a quaternary children's hospital and compared procedures in patients ages 1-19 years old with and without BLA that required antimicrobial prophylaxis (AMP) during 2010-2017. Procedures were matched 1:1 by patient age, complex chronic conditions, year of surgery, and National Surgical Quality Improvement Program current procedural terminology category. The primary outcome was SSI as defined by National Healthcare Safety Network. The secondary outcome was AMP protocol compliance as per American Society of Health-System Pharmacists. RESULTS: Of the 11 878 procedures identified, 1021 (9%) had a reported BLA. There were 35 (1.8%) SSIs in the matched cohort of 1944 procedures with no significant difference in SSI rates in BLA procedures (1.8%) compared to no-BLA (1.9%) procedures. Tier 3 AMP was chosen more frequently among BLA procedures (P < .01). Unmatched analysis of all procedures showed that 23.7% of BLA procedures received beta-lactam-AMP (vs. 93.7% of procedures without BLA). There were no major differences in SSI on sensitivity analysis of BLA procedures that did not receive beta-lactam AMP (1.4%) compared to no-BLA procedures with beta-lactam AMP (1.6%). CONCLUSIONS: Our retrospective matched analysis of 1944 pediatric procedures found no increase in SSIs in procedures with reported BLA, which differs from studies in adults. We observed that the choice of beta-lactam-AMP was common, even in BLA procedures. More data are needed to delineate an association between non-beta-lactam AMP and SSI in children.

Tocilizumab for Treatment of Children and Young Adults With Severe Acute COVID-19: Experience at a Quaternary-care Children's Hospital.

We describe the clinical characteristics and outcomes of 16 children and young adults with severe acute COVID-19 who were treated with tocilizumab. Patients who were discharged by day 28 were more likely to be treated with tocilizumab earlier in their COVID-19 illness and had lower ferritin and interleukin-6 levels compared with those who were not discharged by day 28.

An Initiative to Reduce Insulin-Related Adverse Drug Events in a Children's Hospital.

OBJECTIVES: Adverse drug events (ADEs) during hospitalization are common. Insulin-related events, specifically, are frequent and preventable. At a tertiary children's hospital, we sought to reduce insulin-related ADEs by decreasing the median event rate of hyper- and hypoglycemia over a 12-month period. METHODS: Using Lean 6 σ methodology, we instituted a house-wide process change from a single-order ordering process to a pro re nata (PRN) standing order process. The standardized process included parameters for administration and intervention, enabling physician and nursing providers to practice at top of licensure. Automated technology during dose calculation promoted patient safety during dual verification processes. Control charts tracked rates of insulin-related ADEs, defined as hyperglycemia (glucose level >250 mg/dL) or hypoglycemia (glucose level <65 mg/dL). Events were standardized according to use rates of insulin on each nursing unit. The rates of appropriately timed insulin doses (within 30 minutes of a blood sugar check) were assessed. RESULTS: Baseline median house-wide frequencies of hyperglycemic and hypoglycemic episodes were 55 and 6.9 events (per 100 rapid-acting insulin days), respectively. The median time to insulin administration was 32 minutes. The implementation of the PRN process reduced the median frequencies of hyperglycemic and hypoglycemic episodes to 45 and 3.8 events, respectively. The median time to insulin administration decreased to 18 minutes. CONCLUSIONS: A PRN ordering process and education decreased insulin-associated ADEs and the time to insulin dosing compared with single-entry processes. Engaging bedside providers was instrumental in reducing insulin-related ADEs. Strategies that decrease the time from patient assessment to drug administration should be studied for other high-risk drugs.

Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplantation Patients.

Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but data supporting this practice are inconsistent. In addition to concern for lack of benefit, there are also concerns that this practice could increase the rates of Clostridioides difficile (C diff) infections, the incidence of multidrug-resistant organisms (MDRO) or lead to increased incidence of acute graft-versus-host disease (aGVHD) by disrupting the gut microbiome. This study aimed to assess the safety and efficacy of levofloxacin as bacterial prophylaxis in pediatric and young adult patients undergoing allogeneic or autologous HSCT at a single pediatric center. We conducted a retrospective chart review evaluating patients age ≥6 months who underwent HSCT at our center between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin prophylaxis, whereas those who underwent transplantation after April 2018 did receive levofloxacin prophylaxis. Each transplantation was included as a separate episode if the patient underwent more than 1 transplantation during the inclusion time. The primary outcome of this study was the proportion of patients who experienced at least 1 bacterial bloodstream infection (BSI) in the first 100 days post-transplantation. Secondary outcomes included the number of non-levofloxacin antibiotic days post-transplantation, the incidence of aGVHD, the occurrence of C diff infections, and development of MDRO. A total of 370 HSCT recipients with a median age of 6.7 years (range, 0.5 to 39 years) were included in this study. Seventy-two patients had undergone more than 1 transplantation, and thus we had 443 transplantations to observe. Of these, 216 did not include levofloxacin prophylaxis and 227 included levofloxacin prophylaxis. There were no differences in baseline characteristics between the 2 groups except for age; patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs 9.6 years; P = .05). There were no between-group differences in rates of death at 100 days, antibiotic use, fungal infections, or MDRO infections. Patients in the non-prophylaxis group developed more bacterial BSI in the first 100 days post-HSCT (27% versus 17%; P = .004) and more C diff infections (20% versus 9%; P = .003) than patients who received levofloxacin prophylaxis. In addition, more aGVHD was seen in the patients without levofloxacin prophylaxis (P = .014). Levofloxacin prophylaxis given from day -2 of HSCT through engraftment was significantly associated with decreased bacterial BSI in the first 100 days post-transplantation and was not associated with increased risks of C diff, aGVHD, or MDRO. Our study supports the use of levofloxacin prophylaxis in the peritransplantation period. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Distinct Characteristics and Chronology of Amoxicillin-Associated Reactions in Pediatric Acute Care Settings.

BACKGROUND: Amoxicillin-associated reactions (AARs) in children presenting as rashes are common, and recent data suggest that >90% tolerate amoxicillin on re-exposure. However, additional data would help pediatricians and allergists gain confidence in referring and testing children who experienced systemic symptoms perceived as "worrisome," thus leading to urgent medical evaluations. By characterizing the entire spectrum of AAR symptoms in pediatric patients presenting to emergency department (ED)/urgent care (UC) settings, we sought to increase our diagnostic acumen to guide subsequent allergy evaluations. OBJECTIVE: To fully characterize clinical features of rash and systemic symptoms in children presenting to the ED/UC with AARs. METHODS: A retrospective chart review of children seen in the ED/UC from July 1, 2015, to June 30, 2017, was conducted. Clinical features, chronology, and seasonality were detailed, and cases were classified into 3 previously described AAR phenotypes: maculopapular exanthem (MPE), urticaria, and serum sickness-like reactions (SSLRs), if they experienced joint symptoms. RESULTS: Children (n = 668; median age: 1.8 years) presented to the ED/UC with urticaria (44%), MPE (36%), and SSLRs (11%) typically on days 7 to 10 of amoxicillin. Although children with SSLRs were more frequently treated with corticosteroids (28%, P < .0001) and exhibited higher rates of "worrisome" features (fever, angioedema, or gastrointestinal symptoms; 73%, P < .0001), delayed-onset systemic symptoms were identified frequently in all 3 groups. ED/UC reutilization was unexpectedly high with 66 children (10%) returning to the ED/UC for re-evaluation. CONCLUSION: "Worrisome" symptoms are common in children presenting to the ED/UC with AARs. Future studies are needed to determine the impact on subsequent referral and allergy testing.

Predictors of Acute Care Reutilization in Pediatric Patients With Amoxicillin-Associated Reactions.

BACKGROUND: Amoxicillin-associated reactions (AARs) contribute to substantial health care utilization, with a reutilization rate of 10% in pediatric emergency department (ED) and urgent care (UC) settings. OBJECTIVE: To identify predictors of ED/UC reutilization by examining patients' clinical features and providers' management of AARs. METHODS: Through a retrospective chart review of 668 patients presenting with AARs over 2 years to the pediatric ED/UC, we examined clinical features associated with ED/UC reutilization, including rash phenotype, systemic symptoms (fever, angioedema, joint involvement, gastrointestinal symptoms), and providers' management (pharmacologic treatment and counseling). We then constructed a statistical model to predict ED/UC reutilization using stepwise backward model selection. RESULTS: ED/UC reutilizers were more likely to be male (P = .008) and have fever (P = .0001), angioedema (P < .0001), joint involvement (P < .0001), and gastrointestinal symptoms (P = .0001) during their AAR course. Rash phenotypes differed between groups (P < .0001), as ED/UC reutilizers more frequently exhibited urticaria. However, there were no differences in clinical management between groups, including pharmacologic recommendations, at the initial ED/UC encounter. In addition, our statistical model identified younger patients <2 years of age as more likely to reutilize ED/UC resources if providers did not document specific return precautions (odds ratio, 3.6; 95% confidence interval, 1.7-7.7). CONCLUSION: Recognition of clinical features and treatment gaps associated with ED/UC reutilization will guide interventions to optimize care in children presenting with AARs, such as improved anticipatory guidance and early allergy consultation. Prospective studies are needed to determine whether these interventions will reduce ED/UC reutilization and facilitate timely allergy testing.

Single Site Experience of the use of Monoclonal Antibodies for the Treatment of COVID-19 in High-risk Pediatric and Young Adult Patients.

BACKGROUND: Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for the treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. METHODS: Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild-to-moderate COVID-19 disease at Cincinnati Children's Hospital Medical Center from 5/1/2020 to 3/1/2022 were identified retrospectively. Patient data including demographics, adverse events, and outcomes were extracted from patients' charts and summarized by standard descriptive summaries. RESULTS: Ninety-four patients received monoclonal antibody therapy, of which 14 (14.9%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (57.4%) received casirivimab-imdevimab, and 26 (27.6%) received sotrovimab. Ten patients (10.6%) experienced one or more infusion-related adverse event. Of the patients who experienced adverse events, all resolved with cessation of infusion. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 12 patients (12.7%) required additional medical care for ongoing COVID symptoms. Five of these were either hospitalized or received escalation of care while already in the hospital. All subsequently fully recovered. Neither infusion-related adverse events nor progression to hospitalization for ongoing COVID-19 symptoms following monoclonal antibody administration were associated with any particular underlying condition. CONCLUSIONS: Overall, monoclonal antibodies are reasonably well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations.

Inaccurate Glucose Sensor Values After Hydroxyurea Administration.

Objective: To assess the degree, duration, mean absolute relative difference (MARD), and error analysis of discrepant values per continuous glucose monitoring (CGM) systems after hydroxyurea (HU) administration. Research Design and Methods: Inpatient glucometer and CGM data from 16 total pancreatectomy/islet autotransplantation patients using Dexcom Professional G4 and 12 patients using Dexcom G6 were analyzed after daily dosing with HU. Timing of HU dosing and median of 9.5 days of sensor and glucometer values were assessed per patient. Results: A large positive elevation of sensor readings was identified after HU dosing. The greatest discrepancy between glucometer and sensor readings occurred 0.5-2 h after HU administration [G4 (mean 3.0 mmol/L, median 2.4 mmol/L, MARD 55%), G6 (mean 4.2 mmol/L, median 4.6 mmol/L, MARD 91%)]. The discrepancy was <1.1 mmol/L, mean (-0.5 mmol/L) and median (-0.5 mmol/L), MARD 14% (G4) and <1.1 mmol/L, mean (0.3 mmol/L) and median (0.3 mmol/L), MARD 17% (G6), by 6 h after administration. Error analysis with the G6 system found 94% of pairs in clinically acceptable range by 6-9 h after HU administration. Aspirin, also given once daily, did not result in glucose value discrepancy with the G6 system but variability was observed with the G4 system. Conclusions: There was marked elevation of sensor glucose readings compared with glucometer values [up to 13.9 mmol/L (G4), 13 mmol/L (G6)] from 0.5 to 6 h after HU administration. It is important to counsel a patient using a Dexcom CGM system and HU therapy on this finding and to advise reliance on glucometer testing for accurate glucose assessment up to 6-9 h after HU administration.

Improved Glycemic Outcomes with Early Initiation of Insulin Pump Therapy in Pediatric Postoperative Total Pancreatectomy with Islet Autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44-6.66 mmol/L (80-120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

Continuous Glucose Monitoring in the Intensive Care Unit Following Total Pancreatectomy with Islet Autotransplantation in Children: Establishing Accuracy of the Dexcom G6 Model.

Hyperglycemia is detrimental to postoperative islet cell survival in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). This makes continuous glucose monitoring (CGM) a useful management tool. We evaluated the accuracy of the Dexcom G6 CGM in pediatric intensive care unit patients following TPIAT. Twenty-five patients who underwent TPIAT had Dexcom G6 glucose values compared to paired serum glucose values. All paired glucose samples were obtained within 5 minutes of each other during the first seven days post TPIAT. Data were evaluated using mean absolute difference (MAD), mean absolute relative difference (MARD), %20/20, %15/15 accuracy, and Clarke Error Grid analysis. Exclusions included analysis during the CGM "warm-up" period and hydroxyurea administration (known drug interference). A total of 183 time-matched samples were reviewed during postoperative days 2-7. MAD was 14.7 mg/dL and MARD was 13.4%, with values of 15.2%, 14.0%, 12.1%, 11.4%, 13.2% and 14.1% at days 2, 3, 4, 5, 6 and 7, respectively. Dexcom G6 had a %20/20 accuracy of 78%, and a %15/15 accuracy of 64%. Clarke Error Grid analysis showed that 77% of time-matched values were clinically accurate, and 100% were clinically acceptable. The Dexcom G6 CGM may be an accurate tool producing clinically acceptable values to make reliable clinical decisions in the immediate post-TPIAT period.