Invasive fungal diseases (IFDs) have been documented among the causes of post-chimeric antigen receptor-T (CAR-T) cell immunotherapy complications, with the incidence of IFDs in CAR-T cell therapy recipients being measured between 0% and 10%, globally. IFDs are notorious for their potentially life-threatening nature and challenging diagnosis and treatment. In this review, we searched the recent literature aiming to examine the risk factors and epidemiology of IFDs post-CAR-T infusion. Moreover, the role of antifungal prophylaxis is investigated. CAR-T cell therapy recipients are especially vulnerable to IFDs due to several risk factors that contribute to the patient’s immunosuppression. Those include the underlying hematological malignancies, the lymphodepleting chemotherapy administered before the treatment, existing leukopenia and hypogammaglobinemia, and the use of high-dose corticosteroids and interleukin-6 blockers as countermeasures for immune effector cell-associated neurotoxicity syndrome and cytokine release syndrome, respectively. IFDs mostly occur within the first 60 days following the infusion of the T cells, but cases even a year after the infusion have been described. Aspergillus spp., Candida spp., and Pneumocystis jirovecii are the main cause of these infections following CAR-T cell therapy. More real-world data regarding the epidemiology of IFDs and the role of antifungal prophylaxis in this population are essential.

OBJECTIVES: Development of antimicrobial stewardship programs (ASPs) is strategy for prevention and management of emergence of antimicrobial-resistant organisms. In this study, we systematically reviewed the literature on antimicrobial stewardship interventions in PICUs and analyzed approaches, structure, implementation, and outcomes of the ASPs. DATA SOURCES: PubMed and Scopus databases were systematically searched for studies published from January 1, 2007, to December 31, 2020, reporting interventions on judicious use of antimicrobials in PICUs (last search performed February 28, 2021). DATA SELECTION: Studies that evaluated an intervention in a PICU setting or both in PICU and other settings and reported separate results for PICU were eligible for full-text review. Studies that had implemented stewardship in the entire hospital, including the PICU, but without presenting dedicated PICU data were excluded from the analysis. DATA EXTRACTION: The strategy of intervention, structure of ASP team, implementation, and outcomes were assessed with a checklist tool for all studies included in the analysis. Risk of bias was assessed with the Cochrane Risk-of-Bias in Nonrandomized studies of Interventions tool. DATA SYNTHESIS: Thirteen articles were found: 11 that applied ASP in PICUs, and two at hospital level. All PICU-dedicated ASPs applied a multimodal intervention combining strategies simultaneously; audit with feedback (6/11) and facility-specific clinical practice guidelines (7/11) were the most common strategies. A multidisciplinary team was formulated in all ASPs except for three biomarker-based interventions. Six of 11 studies included techniques to enhance behavior change and one implemented a behavior-based intervention. Antibiotic consumption was evaluated in all ASPs, cost in three of 11, antibiotic resistance in one of 11, length of hospitalization in six of 11, and mortality in eight of 11. All hospital-wide ASPs used audit with feedback in addition to facility-specific clinical practice guidelines and assessed antimicrobial consumption, expenditures, length of stay, and mortality. CONCLUSIONS: The prevalence of ASPs in PICUs is limited, and few programs follow all of the currently available recommendations.

Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal treatment approach has been a matter of debate. We conducted a search in the PubMed database and supplemented it with a manual search to retrieve additional papers eligible for inclusion. We retrieved 13 case reports and case series, from which we summarized that the current trend is to approach each patient with a personalized treatment plan. This consists of a combination of local debulking surgery and adjuvant or neoadjuvant chemotherapy (NACT). Effort is made in every approach to avoid radiation for the sake of preserving fertility. Radical surgeries and radiation still have a role to play in extensive disease and in cases of relapse. Despite the rarity and aggressiveness of this tumor, disease-free survival and overall prognosis is excellent, especially when it is diagnosed early, compared with other subtypes of rhabdomyosarcoma (RMS). We conclude that the practice of a multidisciplinary approach is appropriate, with favorable outcomes; however, larger-scale studies need to be organized to have a definite consensus on optimal management.

Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients’ demographics, outcome, and adverse event (AE) data were recorded. Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Antimicrobial resistance has become a significant public health problem globally with multidrug resistant Gram negative (MDR-GN) bacteria being the main representatives. The emergence of these pathogens in neonatal settings threatens the well-being of the vulnerable neonatal population given the dearth of safe and effective therapeutic options. Evidence from studies mainly in adults is now available for several novel antimicrobial compounds, such as new β-lactam/β-lactamase inhibitors (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem/cilastatin–relebactam), although old antibiotics such as colistin, tigecycline, and fosfomycin are also encompassed in the fight against MDR-GN infections that remain challenging. Data in the neonatal population are scarce, with few clinical trials enrolling neonates for the evaluation of the efficacy, safety, and dosing of new antibiotics, while the majority of old antibiotics are used off-label. In this article we review data about some novel and old antibiotics that are active against MDR-GN bacteria causing sepsis and are of interest to be used in the neonatal population.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and one of the success stories in cancer therapeutics. Risk-directed therapy based on clinical, biologic and genetic features has played a significant role in this accomplishment. Despite the observed improvement in survival rates, leukemia remains one of the leading causes of cancer-related deaths. Implementation of next-generation genomic and transcriptomic sequencing tools has illustrated the genomic landscape of ALL. However, the underlying dynamic changes at protein level still remain a challenge. Proteomics is a cutting-edge technology aimed at deciphering the mechanisms, pathways, and the degree to which the proteome impacts leukemia subtypes. Advances in mass spectrometry enable high-throughput collection of global proteomic profiles, representing an opportunity to unveil new biological markers and druggable targets. The purpose of this narrative review article is to provide a comprehensive overview of studies that have utilized applications of proteomics in an attempt to gain insight into the pathogenesis and identification of biomarkers in childhood ALL.