Vaccination practices of pediatric oncologists from eight states.

BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.

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.

Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients.

OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients. METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition. RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered. CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.

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.

Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

Brain Magnetic Resonance Imaging in Congenital Cytomegalovirus With Failed Newborn Hearing Screen.

BACKGROUND: In 2013, Utah enacted legislation requiring that infants failing newborn hearing screening be tested for cytomegalovirus infection. As a result, cytomegalovirus-infected infants are being identified because of hearing deficits. The neuroimaging findings in this population have not been characterized. METHODS: Retrospective medical record review was used to identify patients seen at the University of Utah and Primary Children's Hospitals in Salt Lake City, Utah, who failed newborn hearing screening. A cohort of patients with congenital cytomegalovirus infection, brain magnetic resonance imaging (MRI), and sedated auditory brainstem response testing was studied. RESULTS: Seventeen patients were identified; 11 (65%) were female. Confirmatory auditory brainstem response testing, performed at a median age 29 days, showed profound hearing loss in 8 (47%) subjects, severe loss in two (12%), moderate loss in two (12%), and mild loss in three (18%); two (12%) subjects had normal hearing. The diagnosis of cytomegalovirus infection was made at a median age 23 days. Brain imaging was performed at a median age 65 days. Ten (59%) subjects had one or more neuroimaging abnormality. White matter lesions were found in eight (47%) subjects, cysts in three (18%), and stroke in two (12%). Polymicrogyria was identified in two (12%) subjects. Seven (41%) subjects had normal brain MRIs. CONCLUSIONS: These results indicate that most infants whose cytomegalovirus infections were identified after failing newborn hearing screening had abnormal brain MRIs. Our results suggest that brain MRIs should be considered in infants with congenital cytomegalovirus infections who are identified through hearing screening programs.

Influence of provider recommendations to restart vaccines after childhood cancer on caregiver intention to vaccinate.

PURPOSE: We studied the influence of oncology and primary care provider (PCP) recommendations on caregiver intentions to restart vaccines (e.g., catch-up or boosters) after cancer treatment. METHODS: We surveyed primary caregivers ages 18 or older with a child who had completed cancer treatment 3-36 months prior (N = 145) about demographics, child's vaccination status, and healthcare factors (e.g., provider recommendations, barriers, preferences for vaccination). We compared these factors by caregiver's intention to restart vaccines ("vaccine intention" vs. "no intent to vaccinate") using bivariate and multivariable analyses. RESULTS: Caregivers were primarily ages 30-39 years (54.9%), mothers (80.6%), college graduates (44.4%), non-Hispanic (89.2%), and married (88.2%). Overall, 34.5% of caregivers did not know which vaccines their child needed. However, 65.5% of caregivers reported vaccine intention. Fewer caregivers with no intention to vaccinate believed that vaccinating their child helps protect others (85.4 vs. 99.0%, p < 0.01), that vaccines are needed when diseases are rare (83.7 vs. 100.0%, p < 0.01), and that vaccines are safe (80.4 vs. 92.6%, p = 0.03) and effective (91.5 vs. 98.9%, p = 0.04) compared with vaccine intention caregivers, respectively. Provider recommendations increased caregivers' likelihood of vaccine intention (oncologist RR = 1.65, 95% CI 1.27-2.12, p < 0.01; PCP RR = 1.51, 95% CI 1.19-1.94, p < 0.01). CONCLUSIONS: Provider recommendations positively influence caregivers' intention to restart vaccines after childhood cancer. Guidelines are needed to support providers in making tailored vaccine recommendations. IMPLICATIONS FOR CANCER SURVIVORS: Timely vaccination after childhood cancer protects patients against vaccine-preventable diseases during survivorship. Caregivers may benefit from discussing restarting vaccinations after cancer with healthcare providers.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

Clinical and Molecular Epidemiology of Invasive Haemophilus influenzae Serotype a Infections in Utah Children.

BACKGROUND: Following widespread use of the Haemophilus influenzae serotype b (Hib) vaccine, H. influenzae serotype a (Hia) has emerged as an important pathogen in children in some regions. We describe the clinical features and molecular epidemiology of invasive Hia disease in children in Utah over an 11-year period. METHODS: We identified cases of invasive Hia disease, defined as detection of Hia from a normally sterile site, in children aged <18 years from Utah between 2007 and 2017. Medical records were reviewed to determine demographic characteristics and clinical outcomes. Available Hia isolates were genotyped using multilocus sequence typing, and phylogenetic division was determined using sodC polymerase chain reaction. Presence of the putative virulence-associated IS1016-bexA duplication-deletion was evaluated. RESULTS: We identified 51 children with invasive Hia. The average annual incidence was 1.7 cases per 100 000 children aged <5 years; 4.8 cases per 100 000 children aged <1 year. The median age was 11.3 months. The most common clinical presentation was meningitis (53%), followed by pneumonia (14%) and septic arthritis (14%). Twenty-two children (43%) required admission to an intensive care unit; 1 died. Sequence type (ST) 62, phylogenetic division II isolates caused 75% (21/28) of disease. No isolates contained the virulence-associated IS1016-bexA duplication-deletion. CONCLUSIONS: Hia is a significant cause of severe invasive bacterial infection in Utah. The majority of infections were caused by ST62 isolates, a phylogenetic division II Hia type that lacks the IS1016-bexA duplication-deletion. Hia ST62 has not been commonly reported elsewhere, suggesting a unique molecular epidemiology in our population.

HPV vaccination knowledge, intentions, and practices among caregivers of childhood cancer survivors.

The HPV vaccine is an important vaccine for childhood cancer survivors because of their risks of second cancers, yet few survivors receive it. We examined HPV vaccine knowledge among caregivers of childhood cancer survivors, whether their child had received the vaccine, and their intentions to vaccinate. Eligible participants were caregivers (mostly parents) whose child finished cancer treatment at Primary Children's Hospital in Salt Lake City, Utah 3 to 36 months prior to the start of the study (N = 145). Additional analyses were done among caregivers whose child was age-eligible for the HPV vaccine (ages 11 and up; N = 61). We ran descriptive statistics and fit multivariable generalized linear models to identify factors associated with intention to vaccinate and HPV vaccination uptake. Among caregivers whose child had not yet gotten the HPV vaccine, approximately 30% stated they were not likely to get the vaccine for their child and the most commonly cited reason was not enough information (25.2%). Provider discussion about vaccines and side effects (relative risk (RR) = 1.85, 95% CI 1.16-2.94), along with recommendations regarding vaccines after cancer treatment (RR = 1.35, 95% CI 1.06-1.72), led to greater caregiver intention to get the HPV vaccine for their child with cancer. Approximately 40% of age-eligible survivors had gotten at least one dose of the HPV vaccine. Our findings demonstrate a need for oncology-focused interventions to educate families of childhood cancer survivors about the importance of the HPV vaccine after cancer therapy.

Cardiac allograft vasculopathy following fecal microbiota transplantation for recurrent C. difficile infection.

We report the case of a 3-year-old male who developed recurrent Clostridium difficile infection after receiving an orthotopic heart transplant. Despite multiple courses of antibiotics, C. difficile infection was persistent and he underwent a fecal microbiota transplant. The patient responded with resolution of his diarrhea. However, within 2 months he developed severe mixed rejection with high circulating donor-specific antibodies and significant coronary vasculopathy. Organ dysfunction led to the need for re-transplantation. The patient's postoperative course has since been complicated by pneumatosis intestinalis and recurrent C. difficile infection.

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). CONCLUSIONS: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.

Impact of Antimicrobial Stewardship for Pediatric Outpatient Parenteral Antibiotic Therapy.

We developed an outpatient parenteral antibiotic therapy (OPAT) stewardship program in a freestanding children's hospital to improve the appropriateness of OPAT prescribing. Introduction of the program enabled expert review of nearly 90% of the patients being prepared for discharge with OPAT and was associated with a 24% reduction in OPAT use.

Infections in pediatric solid-organ transplant recipients.

Solid-organ transplantation in pediatrics can be a life-saving procedure, but it cannot be accomplished without risk of infection-related morbidity and mortality. Evaluation of the recipient during candidacy and donor during evaluation can assist with identification of risk. Further, risk of infection from the surgical procedure can be mitigated through careful planning and attention to infection prevention processes. Finally, early recognition of infection posttransplant can limit the impact of these events.

Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock.

BACKGROUND: Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. METHODS: We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. RESULTS: Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in ≤1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. CONCLUSIONS: Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in ≤1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death.

Outpatient parenteral antimicrobial therapy in pediatrics: an opportunity to expand antimicrobial stewardship.

We reviewed patient discharges with outpatient parenteral antimicrobial therapy (OPAT) to determine whether outpatient parenteral antimicrobial therapy was modifiable or unnecessary at a large tertiary care children's hospital. At least one modification definitely or possibly would have been recommended for 78% of episodes. For more than 40% of episodes, outpatient parenteral antimicrobial therapy was potentially not indicated.

Clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir in children with cytomegalovirus infection.

INTRODUCTION: Among infants and immunocompromised children cytomegalovirus (CMV) is associated with significant morbidity and mortality. AREAS COVERED: This review describes the clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir for the treatment and prevention of CMV infection in children. EXPERT OPINION: A 24-h ganciclovir area under the concentration versus time curve (AUC0₋24) of 40 - 60 µg h/ml decreased the risk of CMV infection for adults undergoing CMV prophylaxis. For adults undergoing treatment for active CMV disease, a target AUC0₋12 of 40 - 60 µg h/ml has been suggested. The applicability of these targets to children remains uncertain; however, with the most sophisticated dosing regimens developed to date only 21% of patients are predicted to reach these targets. Moving forward, identification of optimal pediatric ganciclovir and valganciclovir dosing regimens may involve the use of an externally validated pediatric population pharmacokinetic model for empirical dosing, an optimal sampling strategy for collecting a minimal number of blood samples for each patient and Bayesian updating of the dosing regimen based on an individual patient's pharmacokinetic profile.