Race and Antibiotic Use for Children Hospitalized With Acute Respiratory Infections.

We sought to evaluate whether children hospitalized with acute respiratory infections experienced differences in antibiotic use by race and ethnicity. We found that likelihood of broad-spectrum antibiotic receipt differed across racial and ethnic groups. Future work should confirm this finding, evaluate causes, and ensure equitable antibiotic use.

Creation of a CF-specific antibiotic spectrum index (ASI) as an antimicrobial stewardship initiative.

Antibiotics are frequently utilized for cystic fibrosis (CF)-related pulmonary exacerbation treatment. The antibiotic spectrum index (ASI) is an antimicrobial stewardship tool developed to compare the relative breadth of individual antibiotics. This study aimed to create two expanded CF-specific ASI scoring indices for use in antimicrobial stewardship research and clinical care. The first scoring index expanded the original ASI to include bacterial microorganisms common to CF airway infections (CF-ASI). The second scoring system only included scores for bacterial microorganisms classically identified in CF airway infections (CF-sASI). Sixty-two antibiotics were evaluated and included in the updated ASIs. When multiple antibiotics are prescribed, we proposed using an additive ASI approach whereby the sum of the individual prescribed antibiotic scores represents the total ASI score. The application of CF-focused ASIs into CF research and stewardship programs can help to optimize antibiotic benefits, minimize harms and allow for increased sustainability of antibiotic use in CF.

Individualized Antibiotic Plans as a Quality Improvement Initiative to Reduce Carbapenem Use for Hematopoietic Cell Transplant Patients at a Freestanding Pediatric Hospital.

BACKGROUND: Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship interventions during HCT are often challenging due to concern for undertreating potential infections. METHODS: In an effort to decrease unnecessary carbapenem exposure for patients undergoing HCT at our pediatric center, we implemented individualized antibiotic plans (IAPs) to provide recommendations for preengraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy (DOT) adjusted per 1000 patient-days for carbapenems, antipseudomonal cephalosporins, and all antibiotics during two 3-year periods immediately before and after the implementation of IAPs to measure the impact of IAP on prescribing behavior. Bloodstream infection (BSIs) and Clostridioides difficile (CD) positivity test rates were also compared between cohorts. Last, providers were surveyed to assess their experience of using IAPs in antibiotic decision making. RESULTS: Overall antibiotic use decreased after the implementation of IAPs (monthly reduction of 19.6 DOT/1000 patient-days; P = .004), with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. More than 90% of providers found IAPs to be either extremely or very valuable for their practice. CONCLUSIONS: Implementation of IAPs in this high-risk HCT population led to reduction in overall antibiotic use without increase in rate of BSI or CD test positivity. The program was well received by providers.

Risk Factors for Development of Pneumatosis Intestinalis after Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Case-Control Study.

The significance of pneumatosis intestinalis (PI) in pediatric patients following hematopoietic stem cell transplantation (HSCT) is poorly understood. A knowledge gap remains with respect to the etiology, risk factors, and evidence-based treatment of these patients. As a result, management is frequently based on each center's clinical practice, without standardization across treatment centers. In this single-center trial, we aimed to validate both previously proposed and additional risk factors for the development of PI and to examine our management and outcomes for these patients. We performed a retrospective case-control study examining risk factors for the development of PI in pediatric HSCT patients at a single tertiary referral children's hospital. We used univariate and multivariable conditional logistic regression analysis to explore differences in pharmacologic and other transplantation-specific risk factors. Between 2012 and 2019, PI was diagnosed in 212 patients at our pediatric hospital, of whom 42 were HSCT recipients. The majority of patients (88%; n = 37 of 42) with PI were diagnosed by X-ray. Eighteen patients (43%) were asymptomatic and diagnosed incidentally after imaging was obtained for standard post-transplantation surveillance or other nonrelated indications. All patients with PI were hospitalized and placed on strict bowel rest while receiving parenteral nutrition and antibiotics. Recurrence of PI occurred in 4 patients (10%) following their initial diagnosis. Increased doses of steroid exposure within 30 days of PI diagnosis (odds ratio [OR], 5.7; 95% confidence interval [CI], 2.1 to 15.3; P = .0006), presence of grade II-IV gastrointestinal acute graft-versus-host disease (GVHD) (OR, 5.3; 95% CI, 1.0 to 28.1; P = .05), and receipt of >50% of total daily nutrition by nasogastric (NG) tube feeds (OR, 22.0; 95% CI, 1.3 to 370.2; P = .03) were identified as independent risk factors for the development of PI. Intensity of the conditioning regimen, exposure to total body irradiation, stem cell source, donor type, HLA matching, use of mycophenolate mofetil, and presence of bacterial or viral infection at the time of PI diagnosis were not demonstrably associated with the development of PI in our study. We conclude that development of asymptomatic PI is a benign condition following HSCT, and that the risk for PI is increased in patients with gastrointestinal GVHD, patients receiving steroid therapy, and patients relying on supplemental NG tube feeds for at least one-half of their total daily nutrition.

Flushing an Offensive Term for Vancomycin Infusion Reaction From the Electronic Medical Record.

BACKGROUND: The medical establishment continues to be complicit in the degradation of native peoples of the United States through the use of the racist phrase "red man syndrome" (RMS) to describe the histamine-release syndrome that accompanies vancomycin infusion. METHODS: Five months after the transition from 1 electronic health record to another at our freestanding children's hospital, our antimicrobial stewardship team reviewed all active allergy records to identify and then replace use of RMS terminology with preferred alternative "vancomycin flushing syndrome." In partnership with institutional stakeholders, we also launched an educational campaign and instituted in the electronic health record an autocorrect functionality to prevent new RMS entries. RESULTS: We identified allergy records for 21 034 individual patients. Vancomycin was an allergen for 445 (2.1%) patients, and RMS-related terminology appeared in 274 (61.6%) of these records; we replaced all RMS instances with the vancomycin flushing syndrome term. During the 3-month period after the intervention, we identified allergy records for 8648 additional patients, with vancomycin as allergen in 65 (0.7%) and with RMS terminology identified and replaced in 29 (44.6%). In addition to the lower rate of RMS among allergy records after the intervention, we detected 3 instances of alternative terminology use. CONCLUSIONS: Implementing an institutional-level change in terminology, even for racist language, requires education, reinforcement, and continued surveillance. To effectively replace this term, we need the support of national stakeholders to remove this language from our medical education systems, our textbooks, and our clinical lexicon.

Evaluation of Intravenous Posaconazole Dosing and Pharmacokinetic Target Attainment in Pediatric Patients.

Limited data exist on intravenous (IV) posaconazole dosing and the risk for hepatotoxicity it confers to children. In this study, we evaluated dosing and resulting trough levels in 10 pediatric patients on IV posaconazole. A therapeutic level in these patients was achieved 95% of the time. We found a median minimum effective dose of 6.55 mg/kg of body weight. No correlation was found between the duration or posaconazole trough level and an increased alanine transaminase level.

Antiviral combination therapy for cytomegalovirus infection in high-risk infants.

BACKGROUND: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection. METHODS: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). RESULTS: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.

Renal Toxicity in Pediatric Patients Receiving Cidofovir for the Treatment of Adenovirus Infection.

Treatment options for adenovirus infection in immunocompromised children are limited. Nephrotoxicity has been associated with cidofovir use, but the rate of cidofovir-associated nephrotoxicity in pediatric patients is unclear. In a retrospective review of patients with adenovirus infection treated with cidofovir, neonates (n = 5) had higher viral loads and shorter times to renal insufficiency than older children (n = 24). Higher weekly doses of cidofovir were associated with greater increases in creatinine levels. Of 29 courses of cidofovir, 9 were complicated by acute kidney injury; in these children, mortality was high. Cidofovir dosing in children needs to be optimized, and other therapeutic alternatives should be developed.

Multidrug-resistant Enterococcus faecium meningitis in a toddler: characterization of the organism and successful treatment with intraventricular daptomycin and intravenous tigecycline.

A case of enterococcal meningitis in a toddler is presented. The organism was highly resistant to all drugs previously used for pediatric Gram-positive meningitis. She was successfully treated with intraventricular and intravenous daptomycin and intravenous tigecycline. The organism was characterized as a member of CC17, a notorious emerging nosocomial clone of Enterococcus faecium.