Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives.

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells-not only T cells, but also natural killers and macrophages-might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging.

Antifungal Use in Immunocompromised Children in Europe: A 12-Week Multicenter Weekly Point Prevalence Survey (CALYPSO).

We prospectively analyzed antifungal use in immunocompromised children through a multicenter 12-week weekly point-prevalence survey in 31 hematology-oncology (HO) and hematopoietic stem cell/solid organ transplant (HSCT/SOT) units of 18 hospitals in 11 European countries. All patients hospitalized and receiving systemic antifungals were included. Ward policies, and weekly ward/patient data were collected.

A Global Analysis of Cases of Mucormycosis Recorded in the European Confederation of Medical Mycology / International Society for Human and Animal Mycology (ECMM / ISHAM) Zygomyco.net Registry from 2009 to 2022.

We analyzed mucormycosis data from the Zygomyco.net registry (2009-2022), encompassing cases from 16 countries. India, Russia and the Czech Republic provided the largest contributions.

Changing Epidemiology of spp. Causing Bloodstream Infections in a Tertiary Hospital in Northern Greece: Appearance of .

Introduction: The epidemiology of candidemia has shifted in the past few decades; drug-resistant species have become more prevalent worldwide. The aim of this retrospective study was to determine the epidemiology of species isolated from hospitalized neonates, children and adults, and to investigate a potential changing susceptibility pattern in a large general tertiary hospital.

Methods: All unique strains isolated from candidemia cases between 1 January 2020 and 15 October 2024 were identified, and their susceptibility profile was characterized.

The Combinational Effect of Enhanced Infection Control Measures and Targeted Clinical Metagenomics Surveillance on the Burden of Endemic Carbapenem and Other β-Lactam Resistance Among Severely Ill Pediatric Patients.

Antimicrobial resistance (AMR) is recognized as one of the most important global public health threats. There is an urgent need to reduce the spread of these multidrug-resistant bacteria (MDR-B), particularly in extremely vulnerable patients. The aim of this study was to investigate whether targeted gene amplification performed directly on clinical samples can be used simultaneously with a bundle of enhanced infection control measures in a Pediatric Intensive Care Unit (PICU) endemic to MDR-B.

Untargeted Blood Lipidomics Analysis in Critically Ill Pediatric Patients with Ventilator-Associated Pneumonia: A Pilot Study.

This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, with ages between 6 months and 15 years, were collected at days 1, 3, 6, and 12, and an untargeted lipidomics analysis was performed using a Ultra high Pressure Liquid Chromatography hyphenated with High Resolution Mass Spectrometry UPLC-HRMS (TIMS-TOF/MS) platform.

Antifungal Drug Usage in European Neonatal Units: A Multicenter Weekly Point Prevalence Study.

Background: Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe.

Methods: CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period.

Successful Treatment of Disseminated Fusariosis in a 15-Month-old Boy With Refractory Acute Lymphoblastic Leukemia Using High-dose Voriconazole.

Background: Infections due to rare molds, such as Fusarium spp., cause severe and difficult-to-control diseases with increasing frequency. Data on fusariosis in children and on the use of voriconazole (VCZ), considered a drug of choice, are scarce in infants and children <2 years of age.

Off-label Use of Ceftazidime/Avibactam in Neonatal Intensive Care Unit: A Real-life Experience and Literature Review.

Background: Multi/extensively drug-resistant bacterial infections have recently increased and new antimicrobial options are needed for difficult-to-treat infections. Ceftazidime/avibactam (CZA) has been approved for patients 3 months to 18 years of age, but real-life data on its off-label use in neonates and young infants are still scarce.

Materials: We report demographic, clinical and microbiologic data as well as outcome and safety of all cases of infants treated with CZA between January 1, 2021 and September 30, 2022 in a tertiary neonatal intensive care unit.

Neonatal Bloodstream Infection with Ceftazidime-Avibactam-Resistant -Producing Carrying .

Background: Although ceftazidime/avibactam (CAZ/AVI) has become an important option for treating adults and children, no data or recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant -harboring carrying and the use of a customized active surveillance program in conjunction with enhanced infection control measures.

Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics.

Use of Newer and Repurposed Antibiotics against Gram-Negative Bacteria in Neonates.

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.

Evaluation of Five Host Inflammatory Biomarkers in Early Diagnosis of Ventilator-Associated Pneumonia in Critically Ill Children: A Prospective Single Center Cohort Study.

Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements of PTX-3, SP-D, s-TREM, PTX-3, IL-1β and IL-8 in the blood or lung could improve the accuracy of VAP diagnosis and follow-up in critically ill children. : A prospective pragmatic study in a Pediatric Intensive Care Unit (PICU) was conducted on ventilated critically ill children divided into two groups: high and low suspicion of VAP according to modified Clinically Pulmonary Index Score (mCPIS).

Antimicrobial Stewardship Programs in PICU Settings: A Systematic Review.

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).

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups.

Epidemiology and outcomes of ventilator-associated events in critically ill children: Evaluation of three different definitions.

Objective: Ventilator-associated pneumonia (VAP) is one of the most common healthcare-associated infections in pediatric intensive care units (PICUs), but its definite diagnosis remains controversial. The CDC Ventilator-Associated Event (VAE) module (validated in adults) constitutes a new approach for VAP surveillance.

Design: We described epidemiological characteristics of PICU VAE cases, investigated possible risk factors, and evaluated 3 different sets of diagnostic VAE criteria.

A Longitudinal Study of Spontaneous Gut Decolonization of Carbapenem-resistant Gram-negative Bacteria in Neonatal and Pediatric Patients.

Background: Antibiotic exposure may convert gut microbiome to reservoir of resistant organisms, including carbapenem-resistant Gram-negative bacteria (CRGNB). Little is known about natural history of spontaneous CRGNB decolonization of neonates/children and their risk to develop CRGNB infections.

Methods: Patients hospitalized in a tertiary care hospital (1 days to 16 years) found to be CRGNB colonized in weekly surveillance cultures during hospitalization (January 2018 to December 2019) were prospectively followed after discharge with monthly rectal cultures for 12 months after colonization until decolonization (3 consecutive negative rectal cultures, ≥1 week apart).

Early initiation of the respiratory syncytial virus season in 2021-2022, Greece.

Respiratory syncytial virus (RSV) is the most common viral pathogen causing respiratory disease in the pediatric population. An unexpected sudden upsurge of RSV infections among children was observed in September 2021 in Greece. Forty-one rhinopharyngeal samples from children under the age of 2 years with confirmed RSV bronchiolitis were tested to identify the genotype(s) of the RSV strain(s).

Emergence of ST39 carbapenem-resistant Klebsiella pneumoniae producing VIM-1 and KPC-2.

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes life-threatening hospital-acquired infections. KPC and VIM carbapenemase production is the main molecular mechanism for carbapenem resistance. The aim of the current study was the genetic characterization of four ST39 CRKP isolates simultaneously producing VIM-1 and KPC-2, obtained in a Greek tertiary hospital.

Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study.

Background: Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.

Methods: 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019.

SARS-CoV-2 molecular testing in Greek hospital paediatric departments: a nationwide study.

As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and aetiology of molecular testing for SARS-CoV-2 in Greek paediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in paediatric departments between March and June 2020.