Knowledge of epidemiology is essential for guiding correct antibiotic prescription, reducing bacteremia-associated mortality, and implementing targeted infection control programs. However, only a few studies have reported on the epidemiology of bloodstream infections (BSIs) in pediatrics. We performed a retrospective analysis of all BSIs (excluding those caused by common skin contaminants) diagnosed from 2006 to 2022 in patients younger than 18 years who were treated at an Italian pediatric tertiary care hospital. Overall, 2395 BSIs were recorded, including 2207 (92.15%) due to bacteria and 188 (7.85%) due to fungi. The incidence rate (BSIs/10,000 hospital discharges, IR) of bacterial BSIs significantly increased during the study period. In particular, BSIs caused by S. aureus (including MRSA), Enterobacterales (including ESBL and AmpC producers), Enterococcus spp., and P. aeruginosa became more common. The frequency of carbapenem-resistant strains was <1% and stable over time. Conversely, there was a significant reduction in the incidence of BSIs due to S. pneumoniae. The BSIs were stratified by patient age, and S. aureus was the most frequent cause of BSIs in all age groups, while E. coli was the most frequent in the Enterobacterales family. S. agalactiae was the third most frequent cause of neonatal early-onset BSIs. The prevalence of Enterococcus spp. increased in the subgroups from 8 days to 5 years of age, while P. aeruginosa became more prevalent in children over 5 years of age. S. aureus was also the most frequent isolate in both community- and hospital-onset BSIs, followed by E. coli. The prevalence of multidrug-resistant (MDR) pathogens was very low. It was <5% for both Gram-positive (i.e., MRSA and VRE) and Gram-negative (ESBL, AmpC, and carbapenem-resistant) pathogens, and MDR pathogens were almost exclusively detected in hospital-onset BSIs. Fungi accounted for just under 8% of BSIs. C. albicans was the most frequently isolated strain, followed by C. parapsilosis. Notably, the IR of fungemia did not change significantly during the study period, in spite of an increase in the absolute number of events. The continuous monitoring of local epidemiology is essential to identify changes in the IRs of pathogens and antibiotic susceptibility and to guide antibiotic treatments, especially in the phase when antibiograms are not yet available.

Background/Objectives: Meropenem is a broad-spectrum antibiotic essential for treating resistant Gram-negative infections in pediatric patients. Current dosing recommendations may not consistently achieve optimal pharmacokinetic (PK) targets, especially in critically ill children. Methods: We conducted a retrospective cohort study at IRCCS Istituto Giannina Gaslini, analyzing 97 plasma levels from 86 pediatric patients (<18 years) hospitalized between January 2020 and December 2023 in the neonatal and pediatric intensive care unit. Patients receiving meropenem for proven or suspected infections were included. Demographic, clinical, and PK parameters were assessed, with a focus on trough concentrations (C_trough). Results: The median age was 25 months, with neonates representing 15.5% of cases. The median C_trough was 2.8 mg/L and was significantly higher in neonates (8.9 mg/L) compared to older patients (2.2 mg/L, p < 0.001). Only 27.8% of patients achieved the target C_trough of >8 mg/L, with estimated glomerular filtration rate (eGFR) being the primary factor influencing these levels. Patients with C_trough > 8 mg/L had a significantly lower eGFR (61 mL/min/1.73 m²) compared to those below this threshold (131 mL/min/1.73 m², p = 0.001). Conclusions: The current meropenem dosing regimen may not reliably meet PK targets in critically ill pediatric patients, particularly those with augmented renal clearance or when treating pathogens with increased meropenem MIC. Our findings suggest that increased dosages and prolonged infusion times may be necessary to optimize therapeutic efficacy against resistant Gram-negative bacteria in this vulnerable population. Further studies are needed to refine dosing strategies and improve patient outcomes.

Background: Urinary tract infections (UTIs) are among the most common bacterial infections in children, and the antibiotic susceptibility in the youngest patients remains poorly understood. This study aimed to describe the distribution of uropathogens and their antibiotic susceptibility, focusing on oral formulations. Methods: Data from the first microbiological isolation, between January 2007 and December 2023, at Istituto Gaslini, in young infants (aged <6 months), were analyzed. Results: We isolated 2473 infants’ first pathogen, with a median age in the sample of 2.8 months and 62.6% male. A total of 2498 bacterial isolates were identified, of which 88.8% were Gram-negative and 11.2% were Gram-positive. Escherichia coli (53%) was the most frequent isolate, followed by Klebsiella pneumoniae (12.3%) and Enterococcus spp. (9.6%). No significant differences were observed between males and females, but infants younger than 3 months exhibited a significantly different pathogen distribution compared to older infants. The pathogen distribution showed significant changes before and after 2015, with a marked increase in Klebsiella pneumoniae isolates post-2015. Escherichia coli showed increases in resistance to amoxicillin-clavulanate and ciprofloxacin after 2015. Conclusions: Escherichia coli remains the most common uropathogen; however, Klebsiella pneumoniae has not only shown a high prevalence but also significant resistance, particularly in recent years.

Background: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population. Description of Cases: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of β-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. Discussion: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.

We analyzed 193 Fanconi anemia patients from the Italian Registry, focusing on hematological outcome, cancer risk, and mortality, both in transplanted (n = 130, 67.4% of the cohort) and non‐transplanted (n = 63, 36.6% of the cohort) patients. After a median follow‐up of 7 years, almost all patients developed cytopenia that was more frequent in patients receiving hematopoietic stem cell transplantation (HSCT). The cumulative overall survival from birth was 91.0% at age 10 years, 71.6% at age 20, and 47.4% at age 30 years; the median survival age was 29.1 years. When stratifying patients by indication for transplantation (moderate vs. severe cytopenia vs. persistent poor prognosis cytogenetic alterations/acute myeloid leukemia), we found a 5‐year cumulative mortality higher, though not significantly (p = 0.281) in the last group. Cancers were the second most common cause of death in the whole cohort after infections. Head and neck squamous cell carcinoma was the most frequent cancer, followed by hematologic neoplasms. The cumulative incidence of solid/hematological malignancy remarkably increased after 20 years of age and was 51.7% at age 40 years. The risk of malignancies was greater in subjects who received HSCT (sub‐distribution azard ratio 2.9, 95% CI: 1.1–7.5, p = 0.024). We also identified a small group of patients with stable or even improved cytopenia over time without transplant, thus confirming that bone marrow failure is not automatic in all patients and heightening the importance of tight monitoring to surveil on the worsening of hematopoietic function and cancer occurrence. Overall, this study provides important findings that may help to make robust clinical decisions.

Objectives: To evaluate the tolerability and safety of extended-dosing liposomal amphotericin B (LAmB) as primary antifungal prophylaxis against invasive fungal disease (IFD) in children receiving chemotherapy for newly diagnosed acute myeloid leukaemia (AML); breakthrough proven or probable IFD was assessed as an exploratory secondary endpoint. Methods: This retrospective, multinational, multicentre observational study included children treated for newly diagnosed AML between January 2019 and December 2023. LAmB was administered according to local protocols at 1 mg/kg three times weekly, 2.5 mg/kg twice weekly or 5 mg/kg once weekly. Clinical and laboratory adverse events (AEs) were assessed to evaluate tolerability and safety. Breakthrough proven or probable IFD, defined according to EORTC/MSG criteria, was recorded as an exploratory secondary outcome. Results: Eighty-six courses of extended-dosing LAmB were analysed. The median age at first LAmB administration was 91 months (IQR 26–156). The median treatment duration was 13 weeks (IQR 3–21) at a median dose of 2.7 mg/kg per infusion, with a median estimated cumulative dose of 77.6 mg/kg (IQR 21.3–110.1). Clinical AEs occurred in 21% of courses, predominantly skin rash and lumbosacral pain. Laboratory AEs were mainly hypokalaemia (48%) and hepatotoxicity (19%), both dose related. Treatment discontinuation due to toxicity occurred in 15% of courses. Breakthrough proven or probable IFD occurred in 3% of cases. Conclusions: Extended-dosing LAmB represents a reasonably well-tolerated mould-active option for primary antifungal prophylaxis in children with newly diagnosed AML, particularly when triazoles are contraindicated or daily intravenous echinocandin administration is impractical; the low observed rate of breakthrough IFD should be interpreted cautiously given the absence of a comparator group.