Antimicrobial stewardship programs represent efficacious measures for reducing antibiotic overuse and improving outcomes in different settings. Specific data on pediatric oncology are lacking. We conducted a systematic review on the PubMed and Trip databases according to the PRISMA guidelines, searching for reports regarding antimicrobial stewardship in pediatric oncology and hematology patients. The aim of the study was to summarize the present literature regarding the implementation of antimicrobial stewardship programs or initiatives in this particular population, and provide insights for future investigations. Nine papers were included in the qualitative analysis: three regarding antifungal interventions, five regarding antibacterial interventions, and one regarding both antifungal and antibacterial stewardship interventions. Variable strategies were reported among the included studies. Different parameters were used to evaluate the impact of these interventions, including days of therapy per 1000-patient-days, infections with resistant strains, safety analysis, and costs. We generally observed a reduction in the prescription of broad-spectrum antibiotics and an improved appropriateness, with reduced antibiotic-related side effects and no difference in infection-related mortality. Antibiotic stewardship programs or interventions are effective in reducing antibiotic consumption and improving outcomes in pediatric oncology hematology settings, although stewardship strategies differ substantially in different institutions. A standardized approach needs to be implemented in future studies in order to better elucidate the impact of stewardship programs in this category of patients.

Febrile neutropenia (FN) is a common complication in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella, Megasphaera, Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called “healthy” GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications.

(1) Background: The impact of inflammation on voriconazole exposure in oncohematological pediatric patients represents a debated issue. We aimed to investigate the impact of serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels on voriconazole exposure in oncohematological pediatric patients requiring allogeneic hematopoietic stem cell transplantation (HCT). (2) Methods: Pediatric patients undergoing allogeneic HCT and receiving therapeutic drug monitoring (TDM)-guided voriconazole as primary antifungal prophylaxis between January 2021 and December 2023 were included. The ratio between concentration and dose (C/D) of voriconazole was used as a surrogate marker of total clearance. A receiving operating characteristic curve analysis was performed by using CRP, PCT, or IL-6 values as the test variable and voriconazole C/D ratio > 0.188 or >0.375 (corresponding to a trough concentration value [C_min] of 3 mg/L normalized to the maintenance dose of 16 mg/kg/day in patients of age < 12 years and of 8 mg/kg/day in those ≥12 years, respectively) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. (3) Results: Overall, 39 patients were included. The median (IQR) voriconazole C_min was 1.7 (0.7–3.0) mg/L. A CRP value > 8.49 mg/dL (AUC = 0.72; 95%CI 0.68–0.76; p < 0.0001), a PCT value > 2.6 ng/mL (AUC = 0.71; 95%CI 0.63–0.77; p < 0.0001), and an IL-6 value > 27.9 pg/mL (AUC = 0.80; 95%CI 0.71–0.88; p < 0.0001) were significantly associated with voriconazole overexposure. Consistent results were found in patients aged <12 and ≥12 years. (4) Conclusions: A single specific threshold of inflammatory biomarkers may be linked to a significantly higher risk of voriconazole exposure in oncohematological pediatric patients after HCT, irrespective of age. Adopting a TDM-guided strategy could be useful for minimizing the risk of voriconazole overexposure.

Numerous studies and international recommendations have investigated risk factors that put childhood cancer survivors (CCSs) at a higher risk of late-onset cancer therapy-related cardiovascular toxicities (CTR-CVTs). While anthracyclines and chest-directed radiotherapy are well-established high-risk treatments, other anticancer therapies, including alkylating agents, antimetabolites, targeted therapies, and hematopoietic stem cell transplantation, also carry potential cardiotoxic effects. The likelihood of developing CTR-CVT is further modulated by the presence of cardiometabolic risk factors, prior occurrence of CTR-CVT during treatment, and certain clinical conditions, which may predispose survivors to long-term cardiovascular complications. This state-of-the-art review summarizes current strategies for stratifying the risk for developing CTR-CVT in CCSs. We then propose a tailored, multimodal approach for guiding cardio-oncological assessments both during treatment and in long-term follow-up, including a structured echocardiographic protocol. Future perspectives include validation of this approach to optimize early detection and personalized management of CTR-CVT.