Clinical outcomes of pediatric osteomyelitis.

BACKGROUND: Osteomyelitis in children may produce severe sequelae. However, the frequency and distribution of such complications by type of osteomyelitis (chronic or acute) is not well described. METHODS: We searched the HealthFacts® database (containing medical information on 68 million individual patients in the United States) with 238 International Classification of Diseases (ICD) version 10 codes for acute osteomyelitis and chronic osteomyelitis appearing in 2015. Outcomes were recorded for each subject, including development of limb length discrepancies, pathologic fractures, mortality, and need for multiple surgeries or prolonged orthopedic care (one to two years following diagnosis). Gender, age and season of diagnosis were also assessed. Chi-square tests were used to compare differences between categorical variables, and t-tests between continuous variables. RESULTS: Eight hundred sixty-nine subjects were included (57.4% male). Children with chronic osteomyelitis were older than those with acute osteomyelitis (median 9.5 years vs 12.0, respectively, p = .0004). Diagnoses were more common in winter (p = .0003). Four subjects died while hospitalized during the study period (two with acute osteomyelitis, two with chronic osteomyelitis). Limb length discrepancies were rare and similarly distributed between infection types (≤ 1.3% of subjects, p = .83). Subjects with chronic osteomyeltis were more likely to require long-term orthopedic follow-up (14.0% vs. 4.8% for acute osteomyelitis, p < .0001), suffer from pathologic fractures (1.5% vs < 1.0%, p = .003) and to require multiple surgeries (46.0% vs. 29.3%, p = .04). CONCLUSIONS: Though infrequent, serious outcomes from osteomyelitis are more common with chronic osteomyelitis than acute osteomyelitis.

The Association of Antimicrobial Prophylaxis With Return Visits After Dog Bites in Children.

OBJECTIVES: Dog bites occur frequently in the United States, yet there are no clear guidelines for prescribing antibiotic prophylaxis in healthy children after a dog bite. The aim of our study was to assess antibiotic prophylaxis and subsequent rates of infection after dog bites in children. We hypothesized a negative association between prophylactic prescription of any antimicrobial and return visit within 14 days for infection. METHODS: In this retrospective cohort study, we assessed the frequency of antibiotic prophylaxis prescribed after dog bite injuries in patients 0 to 18 years old and subsequent return visits for infection using 2016 to 2017 medical and pharmacy claims derived from the IBM MarketScan Research Databases. We used the International Classification of Diseases-10 code W54 for dog bites then used keyword searches to find diagnoses (including infection), wound descriptions, and medications. RESULTS: Over the 2-year period, 22,911 patients were seen for dog bites that were not coded as infected. The majority, 13,043 (56.9%), were prescribed an antibiotic at the initial visit and 9868 (43.1%) were not. Of those prescribed antibiotics, 98 (0.75%; 95% confidence interval [CI], 0.60-0.90) returned with an infection, compared with 59 (0.60%; 95% CI, 0.44-0.75) of those not prescribed antibiotics. Receiving an antibiotic prescription at the initial visit was associated with a reduced rate of return for wound infection only among children whose wounds were repaired or closed. Children not receiving a prescription whose wounds were repaired were more than twice as likely to return with an infection in the subsequent 14 days as children whose wounds were not repaired (odds ratio, 2.2; 95% CI, 1.2-4.0). CONCLUSIONS: Most children are prescribed antibiotics at an initial emergency department visit after a dog bite. However, very few return for infection independent of antimicrobial prophylaxis, which suggests antibiotics are overprescribed in this setting.

Long-Term Outcomes in Children Surviving Tropical Arboviral Encephalitis: A Systematic Review.

BACKGROUND: Survivors of childhood encephalitis often suffer from physical and neurocognitive sequelae, particularly in tropical, resource-limited areas with a large burden of arboviral, neurotropic pathogens and limited resources with which to address chronic morbidities. Research into overall and pathogen-specific outcomes following childhood encephalitis may help identify risk factors for poor outcomes, quantify the burden of sequelae, assist with resource allocation and help focus rehabilitative efforts. However, such research is limited. To this end, we systematically reviewed the literature on this topic to identify gaps in knowledge worthy of future investigation. METHODS: A search of PubMed, Web of Knowledge and the Cochrane databases was performed 10 January through 20 February 2020, using 17 search terms for sequelae and 14 for tropical, arboviral pathogens. Eligible reports demonstrated post-discharge follow-up of ≥3 months and assessment of clinical outcome in a child with an arboviral encephalitis ≤18 years of age at diagnosis. RESULTS: Of 1513 articles, 35 were eligible, comprising 693 children. Japanese encephalitis accounted for 18 articles and 93.2% of all subjects (646 total). Sequelae were documented in ∼60% of subjects overall and in those with Japanese encephalitis. For non-Japanese encephalitis virus encephalitides (47 children), sequelae were found in 78.1%. No studies utilized comprehensive neurocognitive testing or assessed the efficacy of rehabilitative efforts. Only nine studies reported data from ≥1 follow-up visit. CONCLUSION: Investigation into long-term outcomes following tropical childhood encephalitis is limited, particularly for neurocognitive sequelae, serial assessments over time and the effect of rehabilitative measures. LAY SUMMARY: Encephalitis, an infection of the brain, is frequently caused by arboviruses (viruses spread via the bite of infected arthropods, such as mosquitoes) in tropical locales. Following infection, surviving children may be plagued with severe physical and cognitive deficits. Unfortunately, research into the type of deficits, their frequency and their responsiveness to rehabilitative efforts is lacking. We identified and reviewed 35 studies describing outcomes in children recovering from tropical, arboviral encephalitis at least 3 months following hospital discharge. Poor outcomes were common and found in up to 60% of children. Long-term and serial follow-up visits were rare, as was the use of comprehensive neurocognitive testing. No studies assessed the efficacy of rehabilitative measures. Further study into these areas is recommended.

Complete genome sequence of a KI polyomavirus isolated from an otherwise healthy child with severe lower respiratory tract infection.

Unbiased, deep sequencing of a nasal specimen from an otherwise healthy 13-month-old boy hospitalized in intensive care revealed high gene expression and the complete genome of a novel isolate of KI polyomavirus (KIPyV). Further investigation detected minimal gene expression of additional viruses, suggesting that KIPyV was potentially the causal agent. Analysis of the complete genome of isolate NMKI001 revealed it is different from all previously reported genomes and contains two amino acid differences as compared to the closest virus isolate, Stockholm 380 (EF127908). J. Med. Virol. 89:926-930, 2017. © 2016 Wiley Periodicals, Inc.

Atypical causes of bacterial osteoarticular infections in immunocompetent children.

Caring for a child with an osteoarticular infection or considering the possibility of an osteoarticular infection in a child is one of the most common clinical dilemmas encountered by clinicians caring for children. In such a scenario, one most often considers infection with frequently encountered pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae or Kingella kingae. A large variety of opportunistic osteoarticular pathogens may be found in the immunosuppressed patient or the postoperative or post-trauma patient, due to breaches in the immune system and nosocomial or post-traumatic exposure to multiple organisms. However, an enlarging spectrum of less commonly encountered bacterial pathogens is also increasingly appreciated in community-acquired osteoarticular infections in otherwise healthy children, particularly in this era of pneumococcal and Haemophilus influenzae serotype B immunization. Given the limitations of culture-based detection methods in osteoarticular infections and the potentially unique therapeutic and diagnostic approaches necessitated by some of these pathogens, an awareness of these infections is necessary for proper detection and management. This review will discuss less commonly encountered bacterial osteoarticular pathogens that may infect otherwise healthy children, with emphasis on the epidemiology, diagnosis and treatment of each.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States--A Case-Series.

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

Understanding the Procedural Skills Needed in Rural Pediatric Practices: A Survey of Rural Pediatric Providers in the State of New Mexico.

OBJECTIVES: There is little data evaluating procedural skills in current rural pediatric practices. In order to prepare a cadre of pediatricians to work in rural settings, we require an understanding of the unique procedural skills needed by rural pediatric providers. Our objective was to determine how often pediatricians performed various procedural skills, determine the importance of these skills to current practice, and how they differ between rural and urban pediatric providers. METHODS: A survey evaluating pediatrician utilization of the 13 required Accreditation Council Graduate Medical Education procedural skills in current practice was developed and distributed to pediatric providers in New Mexico. Descriptive statistics were used to profile participants and describe survey responses. Chi-square tests were used to evaluate differences by urban setting or IHS. Fisher's exact test was employed to assess differences if cell sizes were less than five. All p-values were two sided with alpha=.05. Benjamini-Hochberg method was used to control for type 1 errors. RESULTS: Fifty-two of 216 pediatric providers responded. The majority surveyed performed each of the 13 procedures less than monthly but competency in many of these procedures is important. Thirty-two respondents submitted free-text responses recommending competence with tracheostomy changes, gastrostomy-tube changes/cares, and circumcision. CONCLUSION: Majority of surveyed pediatricians performed the required procedures less than monthly but deemed several procedures to be important. Rural pediatricians recommended specific procedural skills needed in rural practice. All trainees receive procedural skills training. However, trainees interested in rural practice may need additional training in specific skills different than their non-rural counterparts.

Hantavirus Pulmonary Syndrome: 1993-2018.

OBJECTIVES: From 1993 to 2018, hantavirus infections were reported in 39 states, with hantavirus pulmonary syndrome (HPS) as the most common and fatal manifestation. To identify differences in the presentation of HPS between children and adults, we hypothesized that children with HPS would be diagnosed later in their illness course given the nonspecific clinical features of HPS. METHODS: This was an evaluation of the clinical and demographic characteristics of national HPS cases from 1993 to 2018. Data were from the Centers for Disease Control and Prevention database and 1 state department of health, comprising 97% of US cases. We compared children (0 to 12 years), adolescents (13 to 18 years), and adults using nonparametric and parametric analyses, with additional exploratory analyses to identify clinical variables associated with mortality. RESULTS: Among 719 HPS patients, 22 (3.0%) were aged ≤12 years, 47 (6.5%) were 13 to 18 years old, and the remaining 650 (90.4%) were adults. Overall mortality was 35.4% and did not differ between age groups (P = .8). The time between symptom onset and death differed by age group, with children living a median of 2 days (interquartile range [IQR] 2 to 3), adolescents 4 days (IQR 3 to 5), and adults 5 days (IQR 4 to 8; P = .001). The mean highest hematocrit and median highest creatinine level were significantly associated with mortality in those 0 to 18 years old but not adults. CONCLUSIONS: In our dataset representing the largest study of HPS in the United States, we found that children with HPS died more quickly than adults and that highest hematocrit and creatinine levels were associated with death only among those <19 years old.

Defining Variability in Evaluation and Management of Children with Chronic Osteomyelitis.

Pediatric chronic osteomyelitis is a rare, debilitating condition lacking management guidelines. In a national survey of 162 pediatric infectious disease physicians through the Emerging Infections Network, tremendous variability in diagnostic approaches and management was noted, highlighting a need for a prospective study to better define the spectrum of pathogens and disease.

COVID-19 Vaccine Hesitancy Among Parents: A Qualitative Study.

OBJECTIVES: Addressing parental/caregivers' coronavirus disease 2019 (COVID-19) vaccine hesitancy is critical to improving vaccine uptake in children. Common concerns have been previously reported through online surveys, but qualitative data from KII and focus groups may add much-needed context. Our objective was to examine factors impacting pediatric COVID-19 vaccine decision-making in Black, Spanish-speaking, and rural white parents/caregivers to inform the content design of a mobile application to improve pediatric COVID-19 vaccine uptake. METHODS: Parents/caregivers of children aged 2 to 17 years from groups disproportionately affected by COVID-19-related vaccine hesitancy (rural-dwelling persons of any race/ethnicity, urban Black persons, and Spanish-speaking persons) were included on the basis of their self-reported vaccine hesitancy and stratified by race/ethnicity. Those expressing vaccine acceptance or refusal participated in KII, and those expressing hesitancy in focus groups. Deidentified transcripts underwent discourse analysis and thematic analysis, both individually and as a collection. Themes were revised until coders reached consensus. RESULTS: Overall, 36 participants completed the study: 4 vaccine acceptors and 4 refusers via KIIs, and the remaining 28 participated in focus groups. Participants from all focus groups expressed that they would listen to their doctor for information about COVID-19 vaccines. Infertility was a common concern, along with general concerns about vaccines. Vaccine decision-making was informed by the amount of information available to parents/caregivers, including scientific research; possible positive and negative long-term effects; and potential impacts of vaccination on preexisting medical conditions. CONCLUSIONS: Parents/caregivers report numerous addressable vaccine concerns. Our results will inform specific, targeted interventions for improving COVID-19 vaccine confidence.

Neuroinvasive Onchocerca lupi Infection in a Ten-Year-Old Girl.

The nematode Onchocerca lupi is an emerging human pathogen. Though its life cycle is not well studied, it likely infects humans after a bite from a black fly vector, which in turn acquires infective microfilariae from an infected canid. These microfilariae mature into an infective larval stage within the fly. Among six reported cases in the United States, five involved children, and all occurred in the southwest. In this report, we present a case of O. lupi infection with cervical spine invasion in a healthy 10-year-old girl. She presented with five months of neurological symptoms from a rural and medically underserved area, highlighting a need for clinical vigilance in such settings for this emerging infectious threat in the American southwest.

Genomic characterization of Staphylococcus aureus isolates causing osteoarticular infections in otherwise healthy children.

BACKGROUND: Pediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described. METHODS: We prospectively enrolled 47 children over 3 1/2 years from whom S. aureus was isolated on culture-12 uninfected with skin colonization, 16 with skin abscesses, 19 with osteoarticular infections (four with septic arthritis, three with acute osteomyelitis, six with acute osteomyelitis and septic arthritis and six with chronic osteomyelitis). Isolates underwent whole genome sequencing, with assessment for 254 virulence genes and any mutations as well as creation of a phylogenetic tree. Finally, isolates were compared for their ability to form static biofilms and compared to the genetic analysis. RESULTS: No sequence types predominated amongst osteoarticular infections. Only genes involved in evasion of host immune defenses were more frequently carried by isolates from osteoarticular infections than from skin colonization (p = .02). Virulence gene mutations were only noted in 14 genes (three regulating biofilm formation) when comparing isolates from subjects with osteoarticular infections and those with skin colonization. Biofilm results demonstrated large heterogeneity in the isolates' capacity to form static biofilms, with healthy control isolates producing more robust biofilm formation. CONCLUSIONS: S. aureus causing osteoarticular infections are genetically heterogeneous, and more frequently harbor genes involved in immune evasion than less invasive isolates. However, virulence gene carriage overall is similar with infrequent mutations, suggesting that pathogenesis of S. aureus osteoarticular infections may be primarily regulated at transcriptional and/or translational levels.

Influenza Immunization of Adults During Outpatient Pediatric Visits.

The American Academy of Pediatrics suggests pediatricians may provide influenza immunization to adults accompanying children to outpatient appointments. Analysis of the IBM Watson MarketScan database demonstrated that of 1 546 340 encounters for pediatric influenza immunization in 2016, only 1.5% of encounters with a pediatrician resulted in immunization of an accompanying adult.

Variability in the Use of Novel Diagnostic Technology in Children With Suspected Encephalitis and in the Management of Emerging Encephalitides by Pediatric Infectious Disease Providers.

We surveyed pediatric infectious disease physicians through the Infectious Disease Society of America's Emerging Infections Network regarding the diagnosis and management of encephalitis. We identified practice variations, particularly with the use of new diagnostic modalities and management of autoimmune encephalitides. These findings may inform the creation of updated management guidelines.

Assessment of synovial fluid and serum cytokine levels in children with septic arthritis.

Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. Twelve children (8 controls undergoing orthopedic surgery for non-infectious conditions and 4 with ASA) were prospectively enrolled. Blood and synovial fluid were collected intraoperatively from each subject, and the levels of 40 cytokines were determined using a multiplex assay. Cytokines were organized by function and structure into 12 groups for analysis. The Benjamini-Hochberg method was used to control for type 1 errors, with an a priori false discovery rate of 10%. Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.

Severe Acute Respiratory Syndrome Coronavirus 2: Genomic Observations and Emerging Therapies.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the disease COVID-19, first emerged in late December 2019 in China, and has subsequently become a pandemic with unprecedented clinical impact. The virus appears to more severely affect older individuals and those with co-morbid medical conditions, specifically those with chronic lung disease, obesity, heart failure and diabetes. Fortunately, children appear to be less severely affected, though mortality and severe disease have been reported. In addition, children's role in spreading the disease (potentially through asymptomatic shedding of the virus) remains an important area requiring further investigation. The emergence of SARS-CoV-2 has highlighted the importance of metagenomic next generation sequencing as a tool for pandemic investigation. Though no proven therapeutic options currently exist, ongoing genomic and clinical trial data may help inform the identification and development of both repurposed and novel therapeutic agents for use in this disease.

Portrayal of Immunization in American Cinema: 1925 to 2016.

The American media often disseminates antivaccination messages. Cinema in particular reaches many individuals and influences attitudes regarding high-risk behaviors such as smoking and alcohol use. We hypothesized that negative cinematic portrayals of immunization have increased over the last 3 decades. Films released in the United States featuring immunization through 2016 were identified on IMDb and viewed in their entirety by 2 reviewers. Themes were recorded, and the portrayal of immunization (positive, negative, or mixed) across each decade was assessed in a logistic regression model. Cultural references attributed to films (eg, television references) were recorded from the "connection" feature on IMDb. Fifty relevant films were identified (1925-2016). Negative/mixed portrayals of immunization were more frequent after 1990 (odds ratio = 4.0, 95% confidence interval = 1.2-13.5), and films with positive immunization portrayals garnered significantly fewer cultural references than films with negative/mixed portrayals (mean = 9.2 vs 56.2, P = .048). American cinema features increasingly negative portrayals of immunization.

Effect of Vancomycin Loading Doses on the Attainment of Target Trough Concentrations in Hospitalized Children.

OBJECTIVE: Subtherapeutic vancomycin trough concentrations are common in children and may be associated with suboptimal therapeutic response. Our objective was to determine if vancomycin loading doses safely increase the frequency of target trough attainment in hospitalized children. METHODS: Patients (≥6 months and <18-years-old) who received a vancomycin loading dose between February 1, 2018, and January 30, 2019, were retrospectively enrolled. These patients were compared to a convenience cohort of patients hospitalized between January 1, 2015, and December 31, 2015, who received vancomycin without a loading dose. Target trough concentrations were defined as >15 mg/dL for invasive infections and >10 mg/dL for non-invasive infections. RESULTS: A total of 151 patients were enrolled, with 77 in the control arm and 74 in the loading dose arm. There was no significant difference in the frequency of comorbidities or need for intensive care unit admission between the two arms. Those receiving a vancomycin loading dose were older (mean age 9.1 vs 5.2 years, p < 0.0001). Patients given a loading dose achieved higher mean initial trough values (13.0 mg/dL vs 9.2 mg/dL, p < 0.0001), were more likely to have an initial trough at or above target (37.0% vs 10.4%, p = 0.0001), were more likely to reach target trough values at any point during therapy (52.1% vs 32.9%, p = 0.0081), and attained a target trough concentration more quickly (mean 41.1 hours vs 58.8 hours, p = 0.0118). There were no significant differences in the frequency of serum creatinine elevation or oliguria at the end of therapy. CONCLUSIONS: Vancomycin loading doses may improve the ability to safely obtain target trough values in hospitalized children.