Short-Course Empiric Antibiotics in Children Undergoing Allogeneic Hematopoietic Cell Transplantation.

Fever is common in children undergoing hematopoietic cell transplantation (HCT). Empiric antibiotic (EA) therapy is initiated and often continued until neutrophil engraftment. Prolonged antibiotic exposure reduces microbiome diversity and causes overgrowth of pathogenic organisms, leading to such complications as infections from antibiotic-resistant organisms and Clostridium difficile colitis. Shorter courses of EA therapy have been studied in adults undergoing HCT without significant safety concerns, but data in children are lacking. We instituted a single-center preintervention/ postintervention quality improvement (QI) project to assess the feasibility of short-course EA therapy for first fever in patients undergoing HCT. We aimed to reduce the median duration of broad-spectrum antibiotic use in eligible patients from 20 days in 2020 to 10 days in 2021. Patients were eligible for the intervention, limiting EAs to 7 days for first fever, if they were admitted for their first allogeneic HCT, were afebrile for >24 hours, had no infection requiring systemic treatment, and were hemodynamically stable. Outcome measures included days of EA therapy for first fever and total broad-spectrum antibiotic use during the period of hospitalization, defined as the time from the start of conditioning to 30 days after HCT or hospital discharge, whichever occurred first. Balancing measures included bloodstream infection (BSI), fever, and intensive care (ICU) admission within 3 days of stopping EA therapy. Project criteria were applied retrospectively to patients who underwent HCT in 2020 to construct a preintervention short-course-eligible cohort. During the intervention period, 41 patients underwent allogeneic HCT, of whom 17 (41%) were eligible for short-course EA therapy. Among eligible patients, the median age was 5.3 years, 47% had an underlying malignancy, and 88% received myeloablative conditioning. There were no differences in demographic or HCT characteristics between patients eligible for short-course EA during the intervention and preintervention period (n = 24). The short-course EA schedule was adhered to by 14 of the 17 eligible patients (82%). The duration of EA for first fever and total broad-spectrum antibiotic use was significantly decreased in the short-course EA-eligible patients compared to the preintervention cohort, from a median of 17 days to 8 days and from 20 days to 10 days, respectively (P < .01). Of the 14 patients adhering to short-course EA, 2 experienced a balancing measure of recurrent fever requiring resumption of EA, but no infection was identified. There were no BSIs, ICU admissions, or deaths during the hospitalization period in patients who received short-course EA. In this single-center QI project, short-course EA for initial fever was successfully applied to children undergoing allogeneic HCT using strict criteria and led to a significant decrease in broad-spectrum antibiotic use during hospitalization. These results should be validated in a prospective clinical trial to include the impact of short-course EA on antibiotic-resistant organisms, the intestinal microbiome, and HCT outcomes.

Intent to Vaccinate SARS-CoV-2 Infected Children in US Households: A Survey.

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%, p = 0.03). Common reasons for declining vaccination were concerns about adverse effects and/or vaccine safety. Providing additional facts on vaccine efficacy increased vaccine acceptance. Evidence-based strategies are needed to increase pediatric COVID-19 vaccine uptake.

Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C).

OBJECTIVES: We aimed to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological responses in children hospitalized with multisystem inflammatory syndrome in children (MIS-C) compared with those with coronavirus disease 2019 (COVID-19), those with Kawasaki disease (KD), and hospitalized pediatric controls. METHODS: From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C (n = 10), symptomatic COVID-19 (n = 10), and KD (n = 5) and hospitalized controls (n = 4) at Children's Healthcare of Atlanta. With institutional review board approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin M and immunoglobulin G (IgG), full-length spike IgG, and nucleocapsid protein antibodies using quantitative enzyme-linked immunosorbent assays and SARS-CoV-2 neutralizing antibodies using live-virus focus-reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses. RESULTS: All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R 2 = 0.956; P < .001), nucleocapsid protein antibodies (R 2 = 0.846; P < .001), and neutralizing antibodies (R 2 = 0.667; P < .001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer 6800; 95% confidence interval 3495-13 231) than children with COVID-19 (geometric mean titer 626; 95% confidence interval 251-1563; P < .001), children with KD (geometric mean titer 124; 95% confidence interval 91-170; P < .001), and hospitalized controls (geometric mean titer 85; P < .001). All children with MIS-C also had detectable RBD immunoglobulin M antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with the erythrocyte sedimentation rate (R 2 = 0.512; P < .046) and with hospital (R 2 = 0.548; P = .014) and ICU lengths of stay (R 2 = 0.590; P = .010). CONCLUSIONS: Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.

Burden of Illness in Households With Severe Acute Respiratory Syndrome Coronavirus 2-Infected Children.

We investigated of illness among household members of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children receiving medical care (n = 32). We identified 144 household contacts (HCs): 58 children and 86 adults. Forty-six percent of HCs developed symptoms consistent with coronavirus disease. Child-to-adult transmission was suspected in 7 cases.