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Objective: To describe the implementation of a multi-step antimicrobial stewardship program in a haemato-oncology and stem cell transplantation program unit. Methods: Pre-post quasi-experimental study with two interrupted time-series analyses, conducted between 01/01/2019 and 31/12/2022 in the Paediatric Haemato-Oncology Unit of the Padua Paediatric Hospital. The interventions were: (1) 02/2020: dissemination of febrile neutropenia clinical pathways, (2) April 2021: provision of the clinical pathways via a customized App (Firstline.org) and implementation of a twice-a-week prospective audit and feedback. The main outcome was antibiotic consumption measured by days of administered therapy (DOTs)/1000 patients' days for all antibiotics and most used molecules., Results: The first intervention (clinical pathways) resulted in a decrease in the overall antibiotic use by the haemato-oncology unit, with an abrupt reduction of 3-gen cephalosporins in favor of piperacillin-tazobactam, as indicated by the clinical pathways. Meropenem and glycopeptide use did not vary. The second intervention (antimicrobial stewardship) further decreased total antibiotic consumption, and a significant decline in meropenem, amikacin, and glycopeptides was achieved., Conclusions: Multi-step stewardship based on guidelines dissemination, multidisciplinary team intervention and collaboration ("handshake" stewardship) was highly effective in optimizing guidelines adherence and reducing overprescriptions in a fragile patient cohort., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical considerations: This study was conducted in accordance with the tenets of the Declaration of Helsinki. The study was granted approval by the ethical committee for clinical trials of the province of Padova on April 7th, 2022 (N. AOP2612). Informed consent: Patient informed consent was waived due to the retrospective nature of the study by the ethical committee for clinical trials of the province of Padova, and the use of wards aggregated data provided by thehospital pharmacy, in accordance with the ethical committee for clinical trials of the province of Padova, (© 2024. The Author(s).)

We report a case of Influenza type B (lineage Yamagata) infection in a child who received the live attenuated influenza virus vaccine before being diagnosed with B-cell acute lymphoblastic leukemia. The patient developed a mild disease that persisted for 18 days and resolved without antiviral treatment. The prolonged infection of an attenuated virus in an immunocompromised host might pose a risk of reversion or evolution to a more pathogenic strain. Prompt prevention, identification, and monitoring of similar cases are desirable to avoid the development of severe illness, which could complicate patient management., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres., Methods: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution., Results: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens., Conclusions: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics., (© 2024. The Author(s).)

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis., (© 2022. The Author(s).)

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID-19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID-19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays.

Fusarium species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host's immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of Fusarium solani infection in a 9-year-old child with acute lymphoblastic leukemia (ALL). This patient presented a deep wound in the elbow at diagnosis. During the induction phase of chemotherapy, he developed multiple skin lesions and severe pneumonia; Fusarium solani was cultured from the skin lesions. He was treated with a high dose of liposomal amphotericin B, followed by voriconazole. Starting from this peculiar case, we collected all patients with acute leukemia affected by Fusarium infection, treated in the pediatric Onco-Hematology Division of Padua University Hospital during the last 20 years. We identified another six cases: all these patients were affected by acute myeloid leukemia (AML) and five of them presented a relapsed/refractory disease. Two out of seven patients died because of infection; five patients recovered from infection, but three out of seven died because of leukemia. Skin lesions in immunocompromised patients should rise the suspicion of disseminated fusariosis. Furthermore, considering the emergence of filamentous fungi in immunocompromised patients, we all should be aware of Fusarium infection, reminding us that the diagnosis is important to cure the infection., Competing Interests: The authors declare no conflict of interest.

Background and Objective: Chronic hepatitis C was a frequent complication in patients treated for malignancy until the introduction of anti-HCV screening tests for blood donors. The association between chronic hepatitis C and progression to cirrhosis and hepatocellular carcinoma has been reported in about 20% and 5% of patients, respectively, within 20-30 years of infection. In adult patients, interferon has proved to be effective in decreasing the abnormal values of transaminases and the level of HCV viremia. Our purpose was to assess efficacy of and tolerance to interferon in a group of young patients who had acquired HCV infection during a period of chemotherapy., Design and Methods: Interferon-a (IFN) was administered to 26 adolescents and young adults (13 males, age range 17-36 years; median age 24) with chronic hepatitis C, including 4 with hepatitis B virus co-infection, who had been treated for leukemia or solid tumor 5 to 19 years before joining this trial. Patients were treated with natural IFN alpha at a dose of 4 MU/m(2) thrice weekly for 12 months and followed up for another 6 months thereafter., Results: Nine patients stopped treatment during the first 6 months because of side effects (2 cases) or lack of response. At the end of the trial, 8 (31%) cases had responded, with alanine amino-transferase normalization and clearance of hepatitis C virus (HCV) RNA. A sustained response was only documented in 15% of cases, however, irrespective of any hepatitis B virus co-infection. The 2 patients with HCV genotype 2 were both responders, whereas only 8% of those with genotype 1 responded., Interpretation and Conclusions: These data show that the efficacy of IFN in this series of young patients is similar to that reported for otherwise healthy adults with hepatitis C. Patients with genotype 2 are strong candidates for IFN treatment while other therapeutic strategies should be designed for patients with HCV genotype 1.

Sera of 658 patients who had completed treatment for pediatric malignancy were analyzed by a second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay test to assess the prevalence of hepatitis C virus (HCV)-seropositivity. All HCV-seropositive patients underwent detailed clinical, laboratory, virologic, and histologic study to analyze the course of HCV infection. One hundred seventeen of the 658 patients (17.8%) were positive for HCV infection markers. Among the 117 anti-HCV+ patients, 41 (35%) were also positive for markers of hepatitis B virus infection with or without delta virus infection markers, 91 (77.8%) had previously received blood product transfusions, and 25 (21.4%) showed a normal alanine aminotransferase (ALT) level during the last 5-year follow-up (11 of them never had abnormal ALT levels). The remaining 92 patients showed ALT levels higher than the upper limit of normal range. Eighty-one of 117 (70%) anti-HCV+ patients were HCV-RNA+, with genotype 1b being present in most patients (54%). In univariate analysis, no risk factor for chronic liver disease was statistically significant. In this study, the prevalence of HCV infection was high in patients who were treated for a childhood malignancy. In about 20% of anti-HCV+ patients, routes other than blood transfusions are to be considered in the epidemiology of HCV infection. After a 14-year median follow-up, chronic liver disease of anti-HCV+ positive patients did not show progression to liver failure.