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Background Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking. Methods We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric. Results Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), nonoperative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community-acquired pneumonia (CAP; 118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range, 19%–43%). Conclusions Most PICU patients receive antibiotics. Based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed.

Pediatric central nervous system (CNS) phaeohyphomycosis is a rare invasive fungal infection associated with high mortality.We describe a child with progressive neurologic symptoms whose ultimate diagnosis was Cladophialophora bantiana -associated CNS phaeohyphomycosis. We discuss her clinical presentation, medical and surgical management and review the current literature.A 9-year-old female presented with acute onset of headaches, ophthalmoplegia and ataxia. Initial infectious work-up was negative, including serial fungal cerebrospinal fluid cultures. Over 2 months, she experienced progressive cognitive and motor declines, and imaging revealed worsening meningitis, ventriculitis and cerebritis. Ultimately, Cladophialophora was detected by plasma metagenomic next-generation sequencing (mNGS). Fourth ventricle fluid sampling confirmed the diagnosis of C. bantiana infection. Given the extent of her disease, complete surgical resection was not feasible. She required multiple surgical debridement procedures and prolonged antifungal therapy, including the instillation of intraventricular amphotericin B. With aggressive surgical and medical management, despite her continued neurologic deficits, she remains alive 3 years after her initial diagnosis. To our knowledge, this is one of a few published pediatric cases of CNS phaeohyphomycosis and the first with the causative pathogen identified by plasma mNGS.CNS phaeohyphomycosis is a serious, life-threatening infection. The preferred management includes a combination of surgical resection and antifungal therapy. In cases complicated by refractory ventriculitis, intraventricular antifungal therapy can be considered as adjuvant therapy. Direct sampling of the CNS for pathogen identification and susceptibility testing is the gold standard for diagnosis; however, the use of plasma mNGS may expedite the diagnosis.

Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) is a non-invasive method that may be able to identify thousands of pathogens through a hypothesis-free approach. There is a lack of consensus on how this test compares to conventional microbiologic testing. We conducted a systematic review and meta-analysis of published studies evaluating the accuracy of plasma cf-mNGS in hospitalized patients and present pooled estimates of the positive (PPA) and negative percent agreement (NPA) compared to a composite reference standard that included all conventional microbiological testing and clinical history as assessed by an adjudication panel or clinical treatment team. Five retrospective studies (n = 552) were included. The majority of the patients (56%-88%) were immunocompromised. The pooled PPA was 67% (95% CI, 54%-81%) and the pooled NPA was 70% (95% CI, 63%-77%). The pooled diagnostic performance characteristics suggest that cf-mNGS provides limited evidence for ruling in or out the presence of infection as commonly used.

Objective Atopic dermatitis (AD) is a chronic inflammatory skin disease that is complicated by an increased risk for skin and systemic infections. Preventive therapy for AD is based on skin barrier improvement and anti-inflammatory treatments, whereas overt skin and systemic infections require antibiotics or antiviral treatments. This review updates the pathophysiology, diagnosis, management, controversy of antibiotic use, and potential treatments of infectious complications of AD. Data Sources Published literature obtained through PubMed database searches and clinical pictures. Study Selections Studies relevant to the mechanisms, diagnosis, management, and potential therapy of infectious complications of AD. Results Skin barrier defects, type 2 inflammation, Staphylococcus aureus colonization, and cutaneous dysbiosis are the major predisposing factors for the increased infections in AD. Although overt infections require antibiotics, the use of antibiotics in AD exacerbation remains controversial. Conclusion Infectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening. Preventive therapy of infections in AD emphasizes skin barrier improvement and anti-inflammatory therapy. The use of antibiotics in AD exacerbation requires further studies.

Objectives Few studies describe the impact of antimicrobial stewardship programs (ASPs) on recognizing and preventing diagnostic errors. Handshake stewardship (HS-ASP) is a novel ASP model that prospectively reviews hospital-wide antimicrobial usage with recommendations made in person to treatment teams. The purpose of this study was to determine if HS-ASP could identify and intervene on potential diagnostic errors for children hospitalized at a quaternary care children’s hospital. Methods Previously self-identified “Great Catch” (GC) interventions by the Children’s Hospital Colorado HS-ASP team from 10/2014 through 5/2018 were retrospectively reviewed. Each GC was categorized based on the types of recommendations from HS-ASP, including if any diagnostic recommendations were made to the treatment team. Each GC was independently scored using the “Safer Dx Instrument” to determine presence of diagnostic error based on a previously determined cut-off score of ≤1.50. Interrater reliability for the instrument was measured using a randomized subset of one third of GCs. Results During the study period, there were 162 GC interventions. Of these, 65 (40%) included diagnostic recommendations by HS-ASP and 19 (12%) had a Safer Dx Score of ≤1.50, (Κ=0.44; moderate agreement). Of those GCs associated with diagnostic errors, the HS-ASP team made a diagnostic recommendation to the primary treatment team 95% of the time. Conclusions Handshake stewardship has the potential to identify and intervene on diagnostic errors for hospitalized children.

Relapse of infection due to SARS-CoV-2 has been rarely described and there is little guidance regarding the management of such cases in immunocompromised hosts. We present a case of an adolescent female with B-cell acute lymphoblastic leukemia hospitalized multiple times for symptomatic SARS-CoV-2 infection who was safely treated with 2 courses of remdesivir (RDV) and has had no additional readmissions to date. Though additional studies are needed to confirm the safety and efficacy of an additional course of RDV in the setting of relapsed or prolonged severe COVID-19, our observations suggest that a second course of RDV may be considered.

Suppurative thyroiditis is uncommon in the pediatric population and particularly rare to be caused by fungi. We present a case of Candida tropicalis thyroiditis in an adolescent male with acute lymphocytic leukemia that led to disseminated candidiasis, thyroid storm and eventual total thyroidectomy for source control.

Background Nontyphoidal Salmonella species (NTS) rarely cause musculoskeletal infections in healthy children. Data on NTS musculoskeletal infections in healthy children are limited. No previous studies have directly compared children with NTS musculoskeletal infections with those with Staphylococcus aureus. Methods This was a case-control study of children 30 days-18 years old seen at Texas Children's Hospital between 2010 and 2017 with NTS musculoskeletal infections. Controls were children with S. aureus musculoskeletal infections matched on date of infection. Patients with known predisposing conditions were excluded. Demographic and clinical risk factors between the 2 groups were compared. Results From 2010 to 2017, 27 cases of NTS musculoskeletal infections were identified, 12 (46.0%) of which occurred in healthy children. The control group had 53 patients. Predictors of NTS musculoskeletal infections included exposure to reptiles [odds ratio (OR) 8.50, 95% confidence interval (CI): 11.24-58.23] and preceding gastrointestinal symptoms (OR 5.63, 95% CI: 1.45-21.89). Children with NTS musculoskeletal infections had greater odds of pelvic and/or spinal involvement than S. aureus controls (OR 5.32, 95% CI: 1.42-20.13). Complications occurred in 16.7% of NTS cases versus 32% of S. aureus controls. Conclusions Healthy children with NTS musculoskeletal infections more frequently report reptile exposure and preceding gastrointestinal symptoms and have pelvic and spinal involvement compared with children with musculoskeletal infections due to S. aureus. NTS should be considered as a potential cause of musculoskeletal infections in children with these risk factors. In contrast to previous case reports and case series, children with NTS musculoskeletal infections had a low rate of complications.

Background Antibiotics are prescribed in up to 80% of pediatric intensive care unit (PICU) patients, but multicenter studies systematically evaluating antibiotic indications and appropriateness in this high-utilizing population are lacking. Methods A multicenter point prevalence study was conducted at 10 geographically diverse tertiary care US children’s hospitals. All PICU patients < 21 years of age who were receiving systemic antibiotics at 8:00 AM on each study day were included. Study days occurred in February and March 2019. Data were abstracted by critical care and/or infectious diseases trained clinicians using standardized data collection forms and definitions of antibiotic appropriateness. Results 408 of 732 PICU patients (56%) received 618 antibiotics on the two study days. Empiric therapy for suspected bacterial infections without sepsis was the most common indication for antibiotics (22%), followed by treatment of community-acquired pneumonia and empiric therapy for septic shock (12% each, Figure 1). Overall, 194 antibiotic orders (32%) were classified as inappropriate and 158 patients (39%) received at least one inappropriate antibiotic. Vancomycin, cefepime, and ceftriaxone were the antibiotics most often inappropriately prescribed (Figure 2). Antibiotics prescribed inappropriately for the top 5 indications shown in Figure 1 accounted for 77% of all inappropriate antibiotic use. Prolonged ( >4 days) empiric therapy and prolonged ( >24 hours) post-operative prophylaxis were the most common reasons antibiotics prescribed for these indications were classified as inappropriate. Pneumonia and ventilator-associated infections were the most common infections for which antibiotics were prescribed inappropriately (46%). Reasons for inappropriate antibiotic use included lack of evidence supporting a bacterial infection (no radiographic infiltrate or significant increase in respiratory support) and use of unnecessarily broad antibiotics (Table 1). Conclusion Inappropriate antibiotic use is common in the PICU, particularly for pneumonia. Studies focused on defining optimal treatment strategies, as well as improved diagnostic approaches to curtail prolonged courses of empiric therapy, should be prioritized. Disclosures All authors: No reported disclosures.

Background A proposed etiology of biliary atresia (BA) entails a virus-induced, progressive immune-mediated injury of the biliary system. Intravenous immunoglobulin (IVIg) has demonstrated clinical benefit in several inflammatory diseases. The aim of this study was to determine the therapeutic effects of high dose immunoglobulin (IgG) treatment in the rhesus rotavirus (RRV)-induced mouse model of BA. Methods Newborn mice were infected with RRV and jaundiced mice were given high dose IgG or albumin control. Survival, histology, direct bilirubin, liver immune cell subsets and cytokine production were analyzed. Results There was no difference in overall survival between RRV-infected groups, however high dose IgG resulted in decreased bilirubin, bile duct inflammation, and increased extrahepatic bile duct patency. High dose IgG decreased vascular cell adhesion molecule-1, resulting in limited migration of immune cells to portal tracts. High dose IgG significantly decreased CD4+ T cell production of IL-2, IFN-γ and TNF-α and CD8+ T cell production of IFN-γ, as well as increased levels of regulatory T cells. Conclusions High dose IgG therapy in murine BA dramatically decreased Th1 cell-mediated inflammation and biliary obstruction. This study lends support for consideration of IVIg clinical trials in infants with BA, to diminish the progressive intrahepatic bile duct injury.

Background Colonization with Staphylococcus aureus increases the risk of developing healthcare-associated infections (HAIs) in adults, but its role in pediatrics remains unclear. We hypothesized that use of a S. aureus screening and decolonization protocol for pediatric patients undergoing cardiovascular (CV) surgery would result in a reduction of invasive S. aureus infections. Methods A S. aureus screening and decolonization protocol (Table 1) was implemented for patients undergoing CV surgery at TCH on January 1, 2018. We retrospectively identified and reviewed charts of pediatric patients with S. aureus infections following CV surgery pre-protocol (2017) and post-protocol (January 1, 2018–March 31, 2018). We defined invasive S. aureus infections as: bacteremia, mediastinitis, superficial and deep surgical site infections (SSIs) and ventilator-associated pneumonias (VAPs). A subset of charts were reviewed pre- and post-protocol for methicillin-resistant S. aureus (MRSA) polymerase chain reaction (PCR) result, use of mupirocin and chlorhexidine gluconate (CHG), and choice of intraoperative antibiotic. Data were analyzed with Fisher’s exact. Results Of 694 pediatric CV surgery patients in 2017, we identified 13 patients with 15 invasive S. aureus infections: bacteremia (5), VAP (4), and SSI (6). Twelve of these infections were caused by methicillin-susceptible S. aureus (MSSA) and 3 were MRSA. The median time to infection was 19 days. In the first 3 month post-protocol period, there were 175 pediatric CV surgery patients with 0 invasive S. aureus infections. Seventy-five charts each were reviewed pre- and post-protocol to assess protocol adherence (Figure 1). Post-protocol MRSA screening peaked at 64%, which increased further to 70% when excluding infants

Background Enterobacter species are a major cause of infections in hospitalized children. Treatment is complicated by the presence of a chromosomal AmpC β-lactamase, capable of inactivating certain antibiotics, including third-generation cephalosporins (3GC). Previous studies in adults have reported a 3–19% risk of relapsed bacteremia with 3GC therapy. Data in children regarding risk factors predicting relapse or persistence of infection are lacking. We sought to determine the frequency of and risk factors for relapse or persistence of Enterobacter infection in children. Methods Retrospective study of patients

Background Non-typhoidal Salmonella species (NTS) rarely cause musculoskeletal (MSK) infections in healthy children. Data on clinical presentation and outcomes of NTS MSK infections is limited to case reports and case series. No previous studies have directly compared children with NTS MSK infections to children with MSK infections due to Staphylococcus aureus (SA), the most common cause of MSK infections in children. Methods In a retrospective case–control study children aged 1 month to 18 years seen at Texas Children’s Hospital from 2010 to 2017 with NTS MSK infections were compared with patients with SA MSK infections. Date of infection matched controls were selected 3:1. Patients with known hemoglobinopathies, immunodeficiencies or infections due to penetrating trauma or related to prosthetic devices were excluded. Logistic regression was used to evaluate associations between historical, clinical and laboratory variables and NTS or SA MSK infection. Results From 2010 to 2017, 27 cases of NST MSK infections were identified, 12 of which occurred in healthy children. The control group had 37 patients. The case and control groups had similar baseline demographics. Predictors of NTS MSK infection included exposure to reptiles (odds ratio [OR], 6.86; 95% confidence interval [CI], 1.03–45.60) and a history of preceding diarrhea (OR, 7.25; 95% CI, 1.12–47). No presenting signs or laboratory markers were identified as predictors of NTS MSK infection. Blood cultures were positive in 8 (66.7%) of the NTS MSK cases. Length of hospital stay, duration of fever or complications did not differ significantly between the two groups and children with NTS MSK infections had a low rate of complications (16.7%). Six (50%) patients with NTS infections had unremarkable evaluations for hemoglobinopathies and immunodeficiencies. Conclusion Healthy children with NTS MSK infections often report a history of reptile exposure and preceding diarrhea compared with children with MSK infections due to SA. If such history is obtained, addition of a third-generation cephalosporin to empirically cover for NST should be considered pending blood and tissue cultures. In contrast to previous case reports and case series, children with NTS MSK infections had a lower rate of complications. Disclosures All authors: No reported disclosures.

Asthma is a leading chronic childhood illness in the US. To gain further insight into the pathophysiology of childhood asthma, we studied markers of airway inflammation and possible triggers such as bacterial lipopolysaccharide (LPS) in 18 children with chronic asthma and persistent wheezing who underwent clinically indicated bronchoscopy and bronchoalveolar lavage (BAL). We predominantly found neutrophilic airway inflammation associated with increased levels of IL-8, metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP-1) and MMP-9/TIMP-1 ratio. A significant correlation was found between levels of LPS in BAL and airway neutrophils in BAL from a subgroup of children who had a tendency of increased levels of MMP-9 and TIMP-1, suggesting that increased LPS levels in BAL may contribute to chronic airway inflammation and early remodeling. Our data highlight the importance of defining chronic triggers of early airway inflammation in children and characterizing their inflammation, considering the use of bronchoscopy and BAL. Increased knowledge of airway inflammation in children may help prevent a more severe asthma phenotype and lead to environmental control measures and new treatment strategies to intervene against the establishment of irreversible inflammation.