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The risk of fungal, bacterial, and viral infections is higher in children with hematological and solid malignancies, particularly during periods of profound neutropenia. Although early administration of antimicrobial agents is common, optimizing pharmacological therapy in pediatric patients with cancer is challenging because of their variable pharmacokinetics compared with adults, including differences in body mass and augmented renal clearance, as well as chemotherapy-induced organ toxicity. Therapeutic drug monitoring, which involves measuring drug concentrations in serum or plasma at specific timepoints and adjusting doses accordingly, can be applied to various medications. While standardized targets for all antimicrobial agents in children are lacking, therapeutic drug monitoring appears to be beneficial in preventing serious toxicity and addressing treatment failure or non-compliance. This narrative review aims to analyze current perspectives on therapeutic drug monitoring for antimicrobial drugs in the special population of children with hematological or oncological diseases, including those undergoing hematopoietic cell transplantation. The review provides evidence on the clinical benefits of this method and explores potential future developments in this area., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Febrile infections in children are a common cause of presentation to the emergency department (ED). While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; nowadays, a better understanding of immunochemical pathways has led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models, combining them for serious bacterial infection (SBI) diagnosis in febrile children. Literature analysis shows that inflammatory response is a complex mechanism in which many biochemical and immunological factors contribute to the host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined, and for this reason, it is reasonable to take them both into consideration in the evaluation of febrile children. The potential of machine learning tools, which represent a real novelty in medical practice, in conjunction with routine clinical and biological information, may improve the accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pediatric precision medicine still uncertain. More data from further research are needed to improve clinical practice and decision making using these new technologies.

Introduction: According to the latest report from the World Health Organization (WHO), approximately 10.0 million people fell ill with tuberculosis (TB) in 2020, 12% of which were children aged under 15 years. There is very few experience on treatment of multi-drug resistant (MDR)-TB in pediatrics., Areas Covered: The aim of this review is to analyze and summarize therapeutic options available for children experiencing MDR-TB. We also focused on management of MDR-TB prophylaxis., Expert Opinion: The therapeutic management of children with MDR-TB or MDR-TB contacts is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. A close follow-up with a standardized timeline and a comprehensive assessment of clinical, laboratory, microbiologic and radiologic data is extremely important in these patients. Due to the complexity of their management, pediatric patients with confirmed or suspected MDR-TB should always be referred to a specialized center.

Invasive fungal diseases (IFDs) are a relevant cause of morbidity and mortality in children with cancer. Their correct prevention and management impact patients' outcomes. The aim of this review is to highlight the rationale and novel insights into antifungal prophylaxis and treatment in pediatric patients with oncological and hematological diseases. The literature analysis showed that IFDs represent a minority of cases in comparison to bacterial and viral infections, but their impact might be far more serious, especially when prolonged antifungal therapy or invasive surgical treatments are required to eradicate colonization. A personalized approach is recommended since pediatric patients with cancer often present with different complications and require tailored therapy. Moreover, while the Aspergillus infection rate does not seem to increase, in the near future, new therapeutic recommendations should be required in light of new epidemiological data on Candidemia due to resistant species. Finally, further studies on CAR-T treatment and other immunotherapies are needed in patients with unique needs and the risk of complications. Definitive guidelines on IFD treatment considering the evolving epidemiology of antifungal resistance, new therapeutic approaches in pediatric cancer, novel antifungal drugs and the importance of an appropriate antifungal stewardship are urgently needed.

In children with cancer, chemotherapy can produce cytotoxic effects, resulting in immunosuppression and an augmented risk of febrile neutropenia and bloodstream infections. This has led to widespread use of antibiotic prophylaxis which, combined with intensive chemotherapy treatment, could have a long-term effect on the gastrointestinal microbiome. In this review, we aimed to analyze the current literature about the widespread use of antibiotic prophylaxis in children experiencing infectious complications induced by chemotherapy and its effects on the gut microbiome. Our review of the literature shows that antimicrobial prophylaxis in children with cancer is still a trending topic and, at the moment, there are not enough data to define universal guidelines. Children with cancer experience long and painful medical treatments and side effects, which are associated with great economic and social burdens, important psychological consequences, and dysbiosis induced by antibiotics and also by chemotherapy. Considering the importance of a healthy gut microbiota, studies are needed to understand the impact of dysbiosis in response to therapy in these children and to define how to modulate the microbiome to favor a positive therapeutic outcome.

The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein., Competing Interests: Conflict of interest statement: The author(s) declare that there is no conflict of interest., (© The Author(s), 2020.)