The first 1000 symptomatic pediatric SARS-CoV-2 infections in an integrated health care system: a prospective cohort study.

BACKGROUND: The spectrum of illness and predictors of severity among children with SARS-CoV-2 infection are incompletely understood. METHODS: Active surveillance was performed for SARS-CoV-2 by polymerase chain reaction among symptomatic pediatric patients in a quaternary care academic hospital laboratory beginning March 12, 2020. We obtained sociodemographic and clinical data 5 (+/-3) and 30 days after diagnosis via phone follow-up and medical record review. Logistic regression was used to assess predictors of hospitalization. RESULTS: The first 1000 symptomatic pediatric patients were diagnosed in our institution between March 13, 2020 and September 28, 2020. Cough (52 %), headache (43 %), and sore throat (36 %) were the most common symptoms. Forty-one (4 %) were hospitalized; 8 required ICU admission, and 2 required mechanical ventilation (< 1 %). One patient developed multisystem inflammatory syndrome in children; one death was possibly associated with SARS-CoV-2 infection. Symptom resolution occurred by follow-up day 5 in 398/892 (45 %) patients and by day 30 in 443/471 (94 %) patients. Pre-existing medical condition (OR 7.7; 95 % CI 3.9-16.0), dyspnea (OR 6.8; 95 % CI 3.2-14.1), Black race or Hispanic ethnicity (OR 2.7; 95 % CI 1.3-5.5), and vomiting (OR 5.4; 95 % CI 1.2-20.6) were the strongest predictors of hospitalization. The model displayed excellent discriminative ability (AUC = 0.82, 95 % CI 0.76-0.88, Brier score = 0.03). CONCLUSIONS: In 1000 pediatric patients with systematic follow-up, most SARS-CoV-2 infections were mild, brief, and rarely required hospitalization. Pediatric predictors of hospitalization included comorbid conditions, Black race, Hispanic ethnicity, dyspnea and vomiting and were distinct from those reported among adults.

Risk Factors for Adverse Events in Children Receiving Outpatient Parenteral Antibiotic Therapy.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) can decrease length of hospital stay but is associated with adverse events (AEs). The purpose of this study was to quantify and identify risk factors for OPAT-associated AEs in children. METHODS: Retrospective single-center study of children ≤21 years old discharged on OPAT from January 2016 to April 2019 with infectious diseases follow-up. Demographic and clinical factors and medication and central venous catheter (CVC)-associated AEs were assessed through chart review. Univariable and multivariable analyses were performed. RESULTS: Among 181 OPAT courses, an AE occurred in 70 (39%). Medication AEs occurred in 30 of 181 courses (16.6%). Children residing in an urban area had a 4.5 times higher risk of having a medication-related AE compared with those in a rural area (odds ratio: 4.51; 95% confidence interval: 1.60-12.77; P = .005). CVC AEs occurred in 47 of 181 courses (26%). Every additional day of OPAT increased the odds of having a CVC-related AE by 4% (odds ratio: 1.04; 95% confidence interval: 1.01-1.07; P = .003). Twenty (11.1%) courses resulted in readmission to the hospital because of an AE. CONCLUSIONS: In this cohort, 39% of children experienced an OPAT-associated AE, and CVC AEs were more common than medication AEs. Longer duration of intravenous therapy and urban residence were independently associated with OPAT-associated AEs, highlighting the importance of converting to oral antibiotic therapy as soon as feasible to reduce OPAT-associated AEs.

Use of a Procalcitonin-guided Antibiotic Treatment Algorithm in the Pediatric Intensive Care Unit.

BACKGROUND: The utility of procalcitonin testing in the pediatric intensive care unit (PICU) is not known. We sought to determine the impact of a procalcitonin-guided antibiotic treatment algorithm implemented with antibiotic stewardship (AS) guidance vs. usual care on antibiotic use in critically ill children. METHODS: Single center, pragmatic, randomized prospective clinical trial of critically ill children admitted to an ICU setting and started on intravenous antibiotics from February 15, 2018, to April 11, 2019. Patients were assigned on a monthly basis to either the procalcitonin or usual care arm. The procalcitonin arm had procalcitonin testing on hospital days 0, 1, 2, and 4 and stewardship assistance with algorithm result interpretation. Both arms had routine AS audit and feedback. The primary outcome was median antibiotic days of therapy per patient in the first 14-days after enrollment. RESULTS: Among 270 patients, 137 were in the procalcitonin arm and 133 in the usual care arm. Antibiotic days of therapy (DOT) were not significantly different between the procalcitonin arm (6.6, IQR: 3.1-10.9) and the usual care arm (7.6, IQR: 3-11.8; P = 0.37). More AS recommendations were made in the procalcitonin vs. control arm (54 vs. 37; P = 0.03). Adherence with algorithm-based antibiotic recommendations was high in the procalcitonin arm (70%). CONCLUSIONS: We found no difference in antibiotic DOT between study arms. This trial was underpowered but demonstrates feasibility of using a procalcitonin-guided antibiotic treatment algorithm with AS audit and feedback in the PICU.

Characteristics and clinical features of SARS-CoV-2 infections among ambulatory and hospitalized children and adolescents in an integrated health care system in Tennessee.

Background Little is known regarding the full spectrum of illness among children with SARS-CoV-2 infection across ambulatory and inpatient settings. Methods Active surveillance was performed for SARS-CoV-2 by polymerase chain reaction among asymptomatic and symptomatic individuals in a quaternary care academic hospital laboratory in Tennessee from March 12-July 17, 2020. For symptomatic patients ≤18 years of age, we performed phone follow-up and medical record review to obtain sociodemographic and clinical data on days 2, 7, and 30 after diagnosis and on day 30 for asymptomatic patients ≤18 years. Daily and 7-day average test positivity frequencies were calculated for children and adults beginning April 26, 2020. Results SARS-CoV-2 was detected in 531/10327 (5.1%) specimens from patients ≤18 years, including 46/5752 (0.8%) asymptomatic and 485/4575 (10.6%) specimens from 459 unique symptomatic children. Cough (51%), fever (42%), and headache (41%) were the most common symptoms associated with SARS-CoV-2 infection. SARS-CoV-2-related hospitalization was uncommon (18/459 children; 4%); no children with SARS-CoV-2 infection during the study period required intensive care unit admission. Symptom resolution occurred by follow-up day 2 in 192/459 (42%), by day 7 in 332/459 (72%), and by day 30 in 373/396 (94%). The number of cases and percent positivity rose in late June and July in all ages. Conclusions In an integrated healthcare network, most pediatric SARS-CoV-2 infections were mild, brief, and rarely required hospital admission, despite increasing cases as community response measures were relaxed.

Incidence of Acute Kidney Injury Among Infants in the Neonatal Intensive Care Unit Receiving Vancomycin With Either Piperacillin/Tazobactam or Cefepime.

OBJECTIVES: To determine whether combination therapy with vancomycin and TZP is associated with a higher incidence of acute kidney injury (AKI) compared with vancomycin with cefepime in infants admitted to the NICU. METHODS: This retrospective cohort study included infants in the NICU who received vancomycin/cefepime or vancomycin/TZP for at least 48 hours. The primary outcome was incidence of AKI, which was defined by the neonatal modified Kidney Disease Improving Global Outcomes AKI criteria. RESULTS: Forty-two infants who received vancomycin with cefepime and 58 infants who received vancomycin with TZP were included in the analysis. The median gestational age at birth, birth weight, and dosing weight were lower in the TZP group, but other baseline characteristics were comparable, including corrected gestational age. Two patients (3%) receiving vancomycin/TZP versus 2 patients (5%) receiving vancomycin/cefepime met criteria for AKI during their antibiotic course (p = 1.00). There were no clinically significant changes in serum creatinine or urine output from baseline to the end of combination antibiotic treatment in either group. CONCLUSIONS: Among infants admitted to our NICU, AKI incidence associated with vancomycin and either TZP or cefepime therapy was low and did not differ by antibiotic combination.

Acute Kidney Injury During Treatment with Intravenous Acyclovir for Suspected or Confirmed Neonatal Herpes Simplex Virus Infection.

OBJECTIVE: To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. STUDY DESIGN: We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. RESULTS: We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment. CONCLUSIONS: Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

Impact of a Rapid Blood Culture Diagnostic Test in a Children's Hospital Depends on Gram-Positive versus Gram-Negative Organism and Day versus Night Shift.

Rapid diagnostic tests (RDTs) for bloodstream infections (BSIs) decrease the time to organism identification and resistance detection. RDTs are associated with early deescalation of therapy for Gram-positive BSIs. However, it is less clear how RDTs influence antibiotic management for Gram-negative BSIs and whether RDT results are acted on during off-hours. We performed a single-center, retrospective review of children with BSI and Verigene (VG) testing at a children's hospital. Of the 301 positive cultures included in the study (196 Gram-positive, 44 Gram-negative, 32 polymicrobial, and 29 non-VG targets), the VG result had potential to impact antibiotic selection in 171 cases; among these, antibiotic changes occurred in 119 (70%) cases. For Gram-negative cultures, the Verigene result correlated with unnecessary antibiotic escalation and exposure to broader-spectrum antibiotics than needed. In contrast, for Gram-positive cultures, the VG results correlated with appropriate antibiotic selection. VG results permitted early deescalation for methicillin-susceptible Staphylococcus aureus (MSSA) (19/24 [79%]) and avoidance of antibiotics for skin contaminants (30/85 [35%]). Antibiotic changes occurred more quickly during the day than at night (4.6 versus 11.7 h, respectively; P < 0.05), and antibiotic escalations occurred more quickly than did deescalations (4.1 versus 10.1 h, P < 0.01). In a pediatric institution with a low prevalence of Gram-negative resistance, the VG RDT facilitated antibiotic optimization for Gram-positive BSIs but led to unnecessary escalation of antibiotics for Gram-negative BSIs. The time to action was slower for RDT results reported at night than during the day. Laboratories should consider these factors when implementing blood culture RDTs.

Incidence of Nephrotoxicity Among Pediatric Patients Receiving Vancomycin With Either Piperacillin-Tazobactam or Cefepime: A Cohort Study.

BACKGROUND: Recent studies in adults have found an incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin and piperacillin-tazobactam (TZP) that is greater than that expected with either medication alone. The purpose of this study was to determine whether combination therapy with vancomycin and TZP is associated with an incidence of AKI in pediatric patients higher than that in those on combination therapy with vancomycin and cefepime. METHODS: We performed a retrospective single-center matched-cohort study of pediatric patients who received vancomycin in combination with TZP or cefepime between January 2015 and June 2016. The patients were matched according to chronic disease, age, sex, and number of concomitant nephrotoxic medications at the time of combination antibiotic therapy. The primary outcome was incidence of AKI. Secondary outcomes included differences between groups in time to AKI, resolution of AKI, and effect of vancomycin trough levels on the incidence of nephrotoxicity. Conditional logistic regression was used to compare categorical and continuous variables between treatment groups. Conditional Poisson regression was used to assess the association between AKI and treatment groups. Stratified log-rank tests and Cox proportional hazards models with shared frailty were used to compare the times to AKI according to treatment group. RESULTS: Two hundred twenty-eight matched patients were included. AKI developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and TZP groups, respectively (P < .001). Type of combination therapy remained a significant predictor for AKI in multivariate conditional Poisson analysis in which adjustments were made for age, sex, use of concomitant nephrotoxins, and vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03). AKI developed almost 3 times sooner in the TZP group than in the cefepime group (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity analyses in which adjustment was made for antibiotic indication in addition to the aforementioned variables and excluding those with gastrointestinal infection revealed similar results. CONCLUSION: Among hospitalized children at our institution, combination therapy with vancomycin and TZP was associated with an incidence of AKI higher than that associated with vancomycin and cefepime.

Improvements in Antimicrobial Prescribing and Outcomes in Pediatric Complicated Appendicitis.

BACKGROUND: Complicated appendicitis, characterized by perforation and/or peritonitis, is common in children, and late infectious complications are frequent. The best antibiotic treatment approach is unknown, resulting in substantial variation in care. We evaluated the effects of 2 successive interventions, an antimicrobial stewardship program (ASP) and a condition-specific clinical practice guideline (CPG), on antimicrobial utilization and patient outcomes in these patients. METHODS: The ASP at our institution was begun in March 2012. The CPG, a standardized antibiotic treatment, was implemented in July 2013. We reviewed every case of complicated appendicitis managed with early appendectomy between January 2011 and October 2014. Patients were thus divided into 3 eras based on their exposure to the following: (1) neither intervention, (2) ASP only or (3) both ASP and CPG. We compared measures of antibiotic utilization and clinical outcomes among the 3 eras. RESULTS: A total of 313 patients were included in the study: 91 exposed to neither intervention; 100 exposed to only the ASP; and 122 exposed to both interventions. With ASP implementation, there were declines in the use of unnecessarily broad or toxic antibiotic regimens. With CPG implementation, there was a decrease in total antibiotic utilization and discharges with intravenous antibiotics. Compliance with CPG-recommended antibiotics exceeded 90%. There was no significant change in overall adverse events; there was a decline in the incidence of surgical-site infections in patients exposed to both interventions. CONCLUSIONS: Complicated appendicitis is an important target for antimicrobial stewardship and quality improvement efforts. A condition-specific CPG can improve both antimicrobial utilization and clinical outcomes.

Reducing Antimicrobial Use in an Academic Pediatric Institution: Evaluation of the Effectiveness of a Prospective Audit With Real-Time Feedback.

INTRODUCTION: Antimicrobial use is decreasing across freestanding children's hospitals, predominantly in institutions with antimicrobial stewardship programs (ASPs) in place. A highly effective ASP should effect a greater decrease in use than predicted by existing trends. Antimicrobial stewardship programs depend on clinician adherence to program recommendations, but little is known about factors associated with adherence. METHODS: Parenteral antimicrobial-use data for our institution and 43 additional freestanding children's hospitals were obtained and normalized for patient census. Segmental linear regression was used to compare rates of change of parenteral antimicrobial use before and after ASP implementation. Time-series models were developed to predict use in the absence of intervention. The odds of adherence to ASP recommendations were determined based on provider characteristics and recommendation type. RESULTS: In the 38 months before ASP implementation, parenteral antimicrobial use was decreasing at our hospital by 3.7%/year, similar to the 3.4%/year found across children's hospitals. The rate of change after implementation of the ASP at our hospital was 11.1%/year, compared to 5.6%/year for other hospitals over the same period. Of 643 interventions, teams adhered with recommendations in 495 cases (77.0%). According to adjusted analysis, primary service was not associated with adherence (P = .356). There was an association between adherence and the role of the clinician receiving a recommendation (P = .009) and the recommendation type (P = .009). CONCLUSIONS: Understanding factors associated with adherence to ASP recommendations can help those who administer such programs to strategize interventions for maximizing efficacy. Our findings reveal the value of a formal ASP in reducing use when controlling for secular trends.

Vancomycin Use: Room for Improvement Among Hospitalized Children.

INTRODUCTION: The use of vancomycin is common among hospitalized children. We sought to evaluate the impact of prospective audit with real-time feedback on vancomycin use and pharmacy costs. METHODS: Vancomycin use was evaluated at Monroe Carell Jr Children's Hospital at Vanderbilt (MCJCHV) before and after the implementation of prospective audit with intervention and feedback to providers in 2012. Antibiotic use was compared to academic children's hospitals with established antimicrobial stewardship programs (ASPs). Two similar pediatric academic institutions without an ASP were used as nonintervention controls. Analysis of monthly days of antibiotic therapy (DoT) per 1000 patient-days was performed by interrupted time series analysis. RESULTS: Monthly vancomycin use decreased from 114 DoTs/1000 patient-days to 89 DoTs/1000 patient-days ( P < .0001). We did not find significant differences in the slope of change in vancomycin use between MCJCHV and institutions with ASPs either before or after the intervention ( P = .86 and P = .71, respectively). When compared to children's hospitals without ASPs, the use of vancomycin was significantly lower at MCJCHV ( P < .001). CONCLUSION: The use of vancomycin at academic children's hospitals with an ASP is declining. In our experience, prospective audit with real-time intervention and feedback to providers significantly reduced the use and costs associated with vancomycin.

Effect of a Clinical Practice Guideline for Pediatric Complicated Appendicitis.

IMPORTANCE: Complicated appendicitis is a common condition in children that causes substantial morbidity. Significant variation in practice exists within and between centers. We observed highly variable practices within our hospital and hypothesized that a clinical practice guideline (CPG) would standardize care and be associated with improved patient outcomes. OBJECTIVE: To determine whether a CPG for complicated appendicitis could be associated with improved clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A comprehensive CPG was developed for all children with complicated appendicitis at Monroe Carell Jr Children's Hospital at Vanderbilt, a freestanding children's hospital in Nashville, Tennessee, and was implemented in July 2013. All patients with complicated appendicitis who were treated with early appendectomy during the study period were included in the study. Patients were divided into 2 cohorts, based on whether they were treated before or after CPG implementation. Clinical characteristics and outcomes were recorded for 30 months prior to and 16 months following CPG implementation. EXPOSURE: Clinical practice guideline developed for all children with complicated appendicitis at Monroe Carell Jr Children's Hospital at Vanderbilt. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the occurrence of any adverse event such as readmission or surgical site infection. In addition, resource use, practice variation, and CPG adherence were assessed. RESULTS: Of the 313 patients included in the study, 183 were boys (58.5%) and 234 were white (74.8%). Complete CPG adherence occurred in 78.7% of cases (n = 96). The pre-CPG group included 191 patients with a mean (SD) age of 8.8 (4.0) years, and the post-CPG group included 122 patients with a mean (SD) age of 8.7 (4.1) years. Compared with the pre-CPG group, patients in the post-CPG group were less likely to receive a peripherally inserted central catheter (2.5%, n = 3 vs 30.4%, n = 58; P < .001) or require a postoperative computed tomographic scan (13.1%, n = 16 vs 29.3%, n = 56; P = .001), and length of hospital stay was significantly reduced (4.6 days post-CPG vs 5.1 days pre-CPG, P < .05). Patients in the post-CPG group were less likely to have a surgical site infection (relative risk [RR], 0.41; 95% CI, 0.27-0.74) or require a second operation (RR, 0.35; 95% CI, 0.12-1.00). In the pre-CPG group, 30.9% of patients (n = 59) experienced any adverse event, while 22.1% of post-CPG patients (n = 27) experienced any adverse event (RR, 0.72; 95% CI, 0.48-1.06). CONCLUSIONS AND RELEVANCE: Significant practice variation exists among surgeons in the management of pediatric complicated appendicitis. In our institution, a CPG that standardized practice patterns was associated with reduced resource use and improved patient outcomes. Most surgeons had very high compliance with the CPG.