Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Identifying Clinically Relevant Bacteria Directly from Culture and Clinical Samples with a Handheld Mass Spectrometry Probe.

BACKGROUND: Rapid identification of bacteria is critical to prevent antimicrobial resistance and ensure positive patient outcomes. We have developed the MasSpec Pen, a handheld mass spectrometry-based device that enables rapid analysis of biological samples. Here, we evaluated the MasSpec Pen for identification of bacteria from culture and clinical samples. METHODS: A total of 247 molecular profiles were obtained from 43 well-characterized strains of 8 bacteria species that are clinically relevant to osteoarticular infections, including Staphylococcus aureus, Group A and B Streptococcus, and Kingella kingae, using the MasSpec Pen coupled to a high-resolution mass spectrometer. The molecular profiles were used to generate statistical classifiers based on metabolites that were predictive of Gram stain category, genus, and species. Then, we directly analyzed samples from 4 patients, including surgical specimens and clinical isolates, and used the classifiers to predict the etiologic agent. RESULTS: High accuracies were achieved for all levels of classification with a mean accuracy of 93.3% considering training and validation sets. Several biomolecules were detected at varied abundances between classes, many of which were selected as predictive features in the classifiers including glycerophospholipids and quorum-sensing molecules. The classifiers also enabled correct identification of Gram stain type and genus of the etiologic agent from 3 surgical specimens and all classification levels for clinical specimen isolates. CONCLUSIONS: The MasSpec Pen enables identification of several bacteria at different taxonomic levels in seconds from cultured samples and has potential for culture-independent identification of bacteria directly from clinical samples based on the detection of metabolic species.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-ß-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.

Identification of an Emergent Pathogen, Bartonella vinsonii, Using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis.

Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction.

Acute Flaccid Myelitis Among Hospitalized Children in Texas, 2016.

BACKGROUND: Acute flaccid myelitis is characterized by acute-onset flaccid limb weakness with predominantly gray matter lesions in the spinal cord spanning one or more segments. Rates of full recovery are poor, and there is no standard treatment or definitive cause. METHODS: This is a retrospective review of children diagnosed with acute flaccid myelitis in Texas during 2016. Patients were identified through a Texas collaborative of six hospitals in four major metropolitan areas. Data abstraction included health history, illness presentation, medical treatments, laboratory studies, imaging data, recovery, and ability to perform activities of daily living up to approximately two years from illness onset. RESULTS: Among all sites, 21 patients met inclusion criteria. Treatments varied with the most common being intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. No differences were seen in response to medical treatments. A potential etiology was found in 12 (57%) cases, including four with enterovirus D68. Five cases recovered fully. Of the 16 patients without full recovery, abilities ranged from (1) able to perform all activities of daily living for age independently (n = 5), (2) mild deficits (n = 5), and (3) substantial reliance on caregivers for activities of daily living (n = 6). CONCLUSION: Many reports describe symptoms and outcomes of acute flaccid myelitis, but limited data are available on long-term functional outcomes. We were unable to make a strong case for any single cause or treatment modality. Fortunately, the majority of patients (15, 71%) were able to perform activities of daily living with complete independence or only mild deficits.

Improved Diagnosis and Treatment of Bone and Joint Infections Using an Evidence-based Treatment Guideline.

BACKGROUND: Our institution created a multidisciplinary guideline for treatment of acute hematogenous osteomyelitis (AHO) and septic arthritis (SA) in response to updates in evidence-based literature in the field and existing provider variability in treatment. This guideline aims to improve the care of these patients by standardizing diagnosis and treatment and incorporating up to date evidence-based research into practice. The primary objective of this study is to compare cases before versus after the implementation of the guideline to determine concrete effects the guideline has had in the care of patients with AHO and SA. METHODS: This is an Institutional Review Board-approved retrospective study of pediatric patients age 6 months to 18 years hospitalized between January 2009 and July 2016 with a diagnosis of AHO or SA qualifying for the guideline. Cohorts were categorized: preguideline and postguideline. Exclusion criteria consisted of: symptoms >14 days, multifocal involvement, hemodynamic instability, sepsis, or history of immune deficiency or chronic systemic disease. Cohorts were compared for outcomes that described clinical course. RESULTS: Data were included for 117 cases that qualified for the guideline: 54 preguideline and 63 postguideline. Following the successful implementation of the guideline, we found significant decrease in the length of intravenous antibiotic treatment (P<0.001), decrease in peripherally inserted central catheter use (P<0.001), and an increase in bacterial identification (P=0.040). Bacterial identification allowed for targeted antibiotic therapy. There was no change in length of hospital stay or readmission rate after the implementation of the guideline. CONCLUSION: Utilizing an evidence-based treatment guideline for pediatric acute hematogenous bone and joint infections can lead to improved bacterial diagnosis and decreased burden of treatment through early oral antibiotic use. LEVEL OF EVIDENCE: Level III- retrospective comparative study.

Decreasing Exposure to Radiation, Surgical Risk, and Costs for Pediatric Complicated Pneumonia: A Guideline Evaluation.

OBJECTIVES: This report describes the creation and successful implementation of a complicated pneumonia care algorithm at our institution. Outcomes are measured for specific goals of the algorithm: to decrease radiation exposure, surgical risk, and patient charges without adversely affecting clinical outcomes. METHODS: We describe steps involved in algorithm creation and implementation at our institution. To depict outcomes of the algorithm, we completed a retrospective cohort study of hospitalized pediatric patients with a diagnosis of complicated pneumonia at a single institution between January 2010 and April 2016 who met criteria for the algorithm. Charts were manually reviewed and data were analyzed via Wilcoxon rank sum, χ2, and Fisher's exact tests. RESULTS: Throughout the algorithm creation process, our institution began to see a change in practice. We saw a statistically significant decrease in the number of patients who underwent a chest computed tomography scan and an increase in patients who underwent a chest ultrasound (P < .001). We also saw an increase in the use of chest tube placement with fibrinolytics and a decrease in the use of video-assisted thoracoscopic surgery as the initial chest procedure (P ≤ .001) after algorithm implementation. These interventions reduced related charges without significantly affecting length of stay, readmission rate, or other variables studied. CONCLUSIONS: The collaborative creation and introduction of an algorithm for the management of complicated pneumonia at our institution, combined with an effort among physicians to incorporate evidence-based clinical care into practice, led to reduced radiation exposure, surgical risk, and cost to patient.

Management of Rabies Prophylaxis for Potential Bat Exposures in a Level III Neonatal Intensive Care Unit.

This report describes the unique challenges of managing potential exposure to bats in a neonatal intensive care unit. The outcome demonstrates that rabies post-exposure prophylaxis can be safely administered to preterm infants with evidence that preterm infants are able to develop adequate titers post vaccination. Infect Control Hosp Epidemiol 2017;38:483-485.

Hospitalizations Due to Respiratory Syncytial Virus Outside of the Typical Season.

Objective: Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and viral lower respiratory tract infections in children. It is associated with annual winter epidemics across the United States, typically October through April. Our objective is to describe the clinical characteristics of children hospitalized outside the typical RSV season and to compare them with those admitted during the season. Methods: A retrospective chart review was conducted of all patients who were hospitalized at Children's Hospital of Austin from May 2000 to September 2006 and had a positive RSV antigen test. Descriptive statistics, tests of differences, and associations between patients diagnosed in the off-season versus typical season were conducted. Results: A total of 850 charts of RSV-positive cases were reviewed. Of these, 45 patients (5.3%) were admitted during the off-season. The following variables were statistically significantly associated with diagnosis in the off-season versus typical season: mean birth weight (2704 g vs. 3204 g respectively, p=0.0001); gestational age at birth less than 36 weeks (OR=4.35; 95% CI: 2.2, 8.6); history of neonatal intensive care unit (NICU) admission at birth (OR=6.04; 95% CI: 2.9, 12.5); and multiple birth (OR=3.38; 95% CI: 1.2, 9.2). Conclusions: Infants with RSV infection outside of the typical season were more likely to have been premature, of lower birth weight, the products of multiple births, and admitted to the NICU at birth.

Familial occurrence of Kawasaki syndrome in North America.

OBJECTIVE: To describe families with multiple members affected with Kawasaki syndrome (KS) to increase awareness of the familial occurrence of KS among practitioners who care for these patients. DESIGN: Retrospective review of medical records at 2 medical centers and data collection from remote KS families who contacted the KS Research Program at the University of California, San Diego. RESULTS: Eighteen families with multiple affected members were identified. There were 9 families with 2 affected siblings. In San Diego, 3 (0.7%) of 424 KS families had sibling cases. Nine families were identified with KS in 2 generations or in multiple affected members, yielding a total of 24 KS-affected children. No clear pattern of inheritance could be deduced from these pedigrees, and it is likely that multiple polymorphic alleles influence KS susceptibility. CONCLUSION: Physicians should counsel affected families and make them aware of the potential increased risk of KS among family members.

Infliximab treatment for refractory Kawasaki syndrome.

OBJECTIVE: To evaluate the use of tumor necrosis factor (TNF)-alpha blockade for treatment of patients with Kawasaki syndrome (KS) who fail to become afebrile or who experience persistent arthritis after treatment with intravenous gamma globulin (IVIG) and high-dose aspirin. STUDY DESIGN: Cases were retrospectively collected from clinicians throughout the United States who had used infliximab, a chimeric murine/human immunoglobulin (Ig)G1 monoclonal antibody that binds specifically to human TNF-alpha-1, for patients with KS who had either persistent arthritis or persistent or recrudescent fever > or =48 hours following infusion of 2 g/kg of IVIG. RESULTS: Response to therapy with cessation of fever occurred in 13 of 16 patients. C-reactive protein (CRP) level was elevated in all but one patient before infliximab infusion, and the level was lower following infusion in all 10 patients in whom it was re-measured within 48 hours of treatment. There were no infusion reactions to infliximab and no complications attributed to infliximab administration in any of the patients. CONCLUSION: The success of TNF-alpha blockade in this small series of patients suggests a central role of TNF-alpha in KS pathogenesis. Controlled, randomized clinical trials are warranted to determine the role of anti-TNF-alpha therapy in KS.

Primary group A streptococcal peritonitis in a previously healthy child.

Primary peritonitis in a child without underlying medical conditions is rare outside the neonatal period. A girl with no past medical history presented with acute abdominal pain. Laparotomy revealed primary peritonitis due to group A Streptococcus (serotype emm89). She was treated with antibiotics and immune globulin, and recovered fully.