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.

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.

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.

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.

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.

Decreasing Hospital Observation Time for Febrile Infants.

BACKGROUND: Febrile infants aged 0 to 60 days are often hospitalized for a 36-to-48 hour observation period to rule out invasive bacterial infections (IBI). Evidence suggests that monitoring blood and cerebrospinal fluid (CSF) cultures for 24 hours may be appropriate for most infants. We aimed to decrease the average culture observation time (COT) from 38 to 30 hours among hospitalized infants 0 to 60 days old over 12 months. METHODS: This quality improvement initiative occurred at a large children's hospital, in conjunction with development of a multidisciplinary evidence-based guideline for the management of febrile infants. We included infants aged 0 to 60 days admitted with fever without a clear infectious source. We excluded infants who had positive blood, urine, or CSF cultures within 24 hours of incubation and infants who were hospitalized for other indications (eg, bronchiolitis). Interventions included guideline dissemination, education regarding laboratory monitoring practices, standardized order sets, and near-time identification of failures. Our primary outcome was COT, defined as time between initiation of culture incubation and hospital discharge in hours. Interventions were tracked on an annotated statistical process control chart. Our balancing measure was identification of IBI after hospital discharge. RESULTS: In our cohort of 184 infants aged 0 to 60 days, average COT decreased from 38 hours to 32 hours after structured guideline dissemination and order-set standardization; this decrease was sustained over 17 months. IBI was not identified in any patients after discharge. CONCLUSIONS: Implementation of an evidence-based guideline through education, transparency of laboratory procedures, creation of standardized order sets, and near-time feedback was associated with shorter COT for febrile infants aged 0 to 60 days.

Increased clinical failures when treating acute otitis media with macrolides: a meta-analysis.

BACKGROUND: Macrolide antibiotics are often used to treat children with acute otitis media (AOM); however, the 2004 American Academy of Pediatrics (AAP) and American Academy of Family Physicians guidelines recommend against their use in patients without history of a type I allergic reaction to penicillins. OBJECTIVE: To evaluate via meta-analysis the comparative efficacy of amoxicillin or amoxicillin/clavulanate to that of macrolide antibiotics in the treatment of children with AOM. METHODS: A systematic literature search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted from the earliest available date through September 2008. We used the following MeSH and key words: amoxicillin, amoxicillin/clavulanate, Augmentin, azithromycin, ceftriaxone, clarithromycin, macrolides, AND media, otitis media, and effusion. Included studies were randomized, blinded, and controlled trials evaluating guideline-recommended antibiotics (amoxicillin or amoxicillin/clavulanate) compared to macrolide antibiotics (azithromycin or clarithromycin) in AOM in children. The primary outcome assessed was clinical failure measured between days 10 and 16 after starting antibiotic therapy. Results are reported as relative risks (RRs) with 95% confidence intervals and were calculated using a random-effects model. RESULTS: A total of 10 trials (N = 2766) evaluating children 6 months-15 years old were included in the meta-analysis. Upon meta-analysis, the use of macrolide antibiotics was associated with an increased risk of clinical failure (RR 1.31 [95% CI 1.07 to 1.60]; p = 0.008) corresponding to a number needed to harm of 32. Upon safety analysis, rates of any adverse reaction (RR 0.74 [95% CI 0.60 to 0.90]; p = 0.003) and diarrhea (RR 0.41 [95% CI 0.32 to 0.52]; p < 0.0001) were significantly lower in the macrolide group. CONCLUSIONS: The meta-analysis suggests that patients treated with macrolides for AOM may be more likely to have clinical failures. As such, it supports the current AAP AOM recommendation that macrolides be reserved for patients who can not receive amoxicillin or amoxicillin/clavulanate.

Evaluation for Neonatal HSV in Infants Undergoing Workup for Serious Bacterial Infection: A 5-Year Retrospective Review.

OBJECTIVES: To describe the characteristics of infants evaluated for serious bacterial infection, focusing on empirical testing and treatment of herpes simplex virus (HSV) and describe the characteristics of HSV-positive patients. METHODS: We included infants aged 0 to 60 days undergoing evaluation for serious bacterial infection in the emergency department. This descriptive study was conducted between July 2010 and June 2014 at a tertiary-care children's hospital. Eligible patients were identified on the basis of age at presentation to the hospital and laboratory specimens. Infant characteristics, symptoms on presentation, and laboratory workup were compared between HSV-positive and HSV-negative patients by using the 2-sample t test or the Wilcoxon rank test. RESULTS: A total of 1633 infants were eligible for inclusion, and 934 (57.2%) were 0 to 28 days of age. HSV was diagnosed in 19 infants, 11 of whom had disseminated disease. Compared with those without HSV, HSV-positive infants were younger, less likely to be febrile and to present with nonspecific symptoms, and more likely to have a mother with HSV symptoms (P < .05). Testing from all recommended locations was only performed in 22% of infants. Infants tested or empirically treated with acyclovir had a longer median length of stay compared with children who were not tested or treated (P < .01). CONCLUSIONS: The absence of fever should not preclude a workup for HSV in neonates, and when a workup is initiated, emphasis should be placed on obtaining samples from serum, cerebrospinal fluid, and surface specimens. Physicians may benefit from a guideline for evaluation of HSV with specific guidance on high-risk features of presentation and recommended testing.

Improving the Transition of Intravenous to Enteral Antibiotics in Pediatric Patients with Pneumonia or Skin and Soft Tissue Infections.

BACKGROUND: Despite national recommendations for early transition to enteral antimicrobials, practice variability has existed at our hospital. OBJECTIVE: The aim of this study was to increase the proportion of enterally administered antibiotic doses for Pediatric Hospital Medicine patients aged >60 days admitted for uncomplicated community-acquired pneumonia or skin and soft tissue infections from 44% to 75% in eight months. METHODS: This quality improvement study was conducted at a large, urban, academic children's hospital. The study population included Hospital Medicine patients aged >60 days with diagnoses of pneumonia or skin and soft tissue infections. Interventions included education on intravenous and enteral antibiotic charge differentials, documentation of transition plan, structured discussions of transition criteria, and real-time identification of failures with feedback. Our process measure was the total number of enteral antibiotic doses divided by all antibiotic doses in patients receiving enteral medications on the same day. An annotated statistical process control chart tracked the impact of interventions on the administration route of antibiotic doses over time. Additional outcome measures included antimicrobial costs per patient encounter using average wholesale prices and length of stay. RESULTS: The percentage of enterally administered antibiotic doses increased from 44% to 80% within eight months. Antimicrobial costs per patient encounter and the associated standard deviation of costs for our target diagnoses decreased by 70% and 84%, respectively. Average length of stay did not change. CONCLUSIONS: Standardized communication about criteria for transition from intravenous to enteral antibiotics can lead to earlier transitions for patients with pneumonia or skin and soft tissue infections, subsequently reducing costs and prescribing variability.

Optimizing bactericidal exposure for beta-lactams using prolonged and continuous infusions in the pediatric population.

BACKGROUND: Administration of beta-lactams via prolonged or continuous infusion has been utilized in adults to optimize drug exposure and clinical outcomes. As children exhibit increased drug clearance, this may further the benefit of prolonged or continuous infusions. This dosing approach was applied to several beta-lactams commonly utilized in children. PROCEDURE: A variety of cefepime, ceftazidime, imipenem/cilastatin, meropenem, and piperacillin/tazobactam regimens using administration times of 0.5, 3, or 24 hr infusions were simulated in populations of 2- and 12-year-old children using Monte Carlo techniques. The probability of target attainment (PTA) was calculated for each dosing regimen. Minimum inhibitory concentration (MIC) frequencies for Pseudomonas aeruginosa were obtained for two pediatric acute care institutions in order to calculate cumulative fractions of response (CFR). RESULTS: Standard 0.5 hr infusions resulted in poor PTA for most study agents at their susceptibility breakpoint, whereas 3 hr infusions markedly improved PTA for cefepime (79 to 100%), ceftazidime (80 to 100%), imipenem (41 to 91%), and meropenem (33 to 97%). Piperacillin/tazobactam could not achieve a PTA > 21% for any dosing regimen at its breakpoint, though large improvements were observed at lower MICs. Continuous infusion regimens resulted in similar PTA results to the same dose administered as 3 hr infusions. CFR values for all drugs at both institutions improved when 3 hr or continuous infusions were employed. CONCLUSIONS: Prolonged and continuous infusion dosing strategies improved the likelihood of obtaining bactericidal targets for these beta-lactams in a simulated pediatric population. Based on these data, pediatric studies employing these strategies are warranted.