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, thrombocy-topenia 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.

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 (AMS) interventions during HCT are often challenging due to concern for undertreating potential infections. 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 pre-engraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy adjusted per 1000 patient days (DOT/1000 pt-days) for carbapenems, anti-pseudomonal 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 infections (BSI) and Clostridioides difficile (CD) positive test rates were also compared between cohorts. Lastly, providers were surveyed to assess their experience of using IAPs in antibiotic decision-making. Overall antibiotic use decreased after the implementation of IAP (monthly reduction of 19.6 DOT/1000 pt-days, p=0.004) with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. Over 90% of providers found IAPs to be either extremely or very valuable for their practice. 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.

Background/Objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases. Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases were recruited through an existing clinical trial. Using an iterative survey and in-person discussions, experts provided input on priority areas, which were thematically grouped and refined across rounds. Structured feedback supported real-time refinement and consensus-building. Results: Twenty experts participated in the process, generating 25 priority items in Round 1 through open-ended responses. These were narrowed to seven key priorities through structured voting and discussion. The final items were clustered into three intersecting themes: Care Settings, Prescriptions, and Strategies. Care Settings focused on high-impact areas such as outpatient clinics and intensive care units, where misuse is common and/or care is complex. The prescriptions theme prioritized shorter durations and narrow-spectrum agents. The strategy theme highlighted the need for outcome-based metrics, improved diagnostic stewardship, and routine tracking of patient outcomes to guide and assess stewardship efforts. Conclusions: This expert consensus identified key priorities for pediatric ASPs, providing a foundation for future interventions. Findings can be used to inform policy and practice, improving the appropriate use of antimicrobials in pediatrics and combating AMR.

We assessed implementation of a local intravenous-to-enteral antimicrobial transition protocol for pediatric hematology/oncology and bone marrow transplant patients with bacterial or candidal bloodstream infection and central line removal. Among 76 cases, 57 met protocol criteria. Enteral antimicrobials were used in 29 (50.8%) cases meeting eligibility criteria for conversion.