A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis. A comprehensive literature search was carried out in Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for studies assessing PCT accuracy in the diagnosis of sepsis in children and neonates with suspected sepsis. Studies in which the presence of infection had been confirmed microbiologically or classified as “probable” by chart review were included. Studies comparing patients to healthy subjects were excluded. We analysed data on neonates and children separately. Our primary outcome was the diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary outcomes we analysed PCT cut-offs 2.5 ng/ml. Pooled sensitivities and specificities were calculated by a bivariate meta-analysis and heterogeneity was graphically evaluated. We included 17 studies, with a total of 1408 patients (1086 neonates and 322 children). Studies on neonates with early onset sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90) and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In the paediatric group it was not possible to undertake a pooled analysis at the PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies. PCT shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological quality are warranted, particularly in neonates, studies considering EOS and LOS separately are needed to improve specificity. PROSPERO Identifier: CRD42016033809 . Registered 30 Jan 2016.

Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children’s hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions. A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected. The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates ( = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for prescribing antibiotic therapy in children was lower respiratory tract infections (LRTI), followed by febrile neutropenia/fever in oncologic patients, while, in neonates, sepsis was the most common indication for treatment. Focusing on prescriptions for LRTI, 43.3% of patients were treated with 3rd generation cephalosporins, followed by macrolides (26.9%), quinolones (16.4%) and carbapenems (14.9%) and 50.1% of LRTI cases were receiving more than one antibiotic. For neutropenic fever/fever in oncologic patients, the preferred antibiotics were penicillins with inhibitors (47.8%), followed by carbapenems (34.8%), aminoglycosides (26.1%) and glycopeptides (26.1%). Overall, the 60.9% of patients were treated with a combination therapy. Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children’s hospital, also considering the continuous and alarming emergence of MDR bacteria.

Antimicrobial stewardship programs (ASPs) and diagnostic stewardship programs (DSPs) are essential strategies for effectively managing infectious diseases and tackling antimicrobial resistance (AMR). These programs can have a complementary impact, i.e., ASPs optimize antimicrobial use to prevent resistance, while DSPs enhance diagnostic accuracy to guide appropriate treatments. This review explores the current landscape of ASPs and DSPs in pediatric care, focusing on key factors, influencing their development, implementation, and evaluation across various settings. A multidisciplinary approach is necessary, involving multiple healthcare professionals to support comprehensive stewardship practices in pediatric care. No single intervention suits all settings, or even the same setting, in different countries; interventions must be tailored to each specific context, considering factors such as hospital capacity, patient complexity, and the parent–child dynamic. It is essential to educate caregivers on optimal antibiotic use through clear, concise messages adapted to their socioeconomic status and level of understanding. The cost-effectiveness of ASPs and DSPs should also be assessed, and standardized metrics should be employed to evaluate success in pediatric settings, focusing on outcomes beyond just antibiotic consumption, such as AMR rates. This manuscript further discusses emerging opportunities and challenges in ASP implementation, offering insights into future research priorities. These include large-scale studies to evaluate the long-term impact of ASPs, cost-effectiveness assessments of pediatric-specific diagnostic tools, and the integration of artificial intelligence to support clinical decision making. Addressing these areas will enhance the effectiveness and sustainability of ASPs, contributing to global efforts to combat AMR and improve pediatric health outcomes.

We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis.

Infections due to carbapenem-resistant Enterobacterales (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes, especially in critically ill patients. Novel beta lactam antibiotics, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol, have been released in recent years to face the emerging challenge of multidrug-resistant (MDR) Gram-negative bacteria. Nonetheless, several novel agents lack pediatric indications approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), leading to uncertain pediatric-specific treatment strategies and uncertain dosing regimens in the pediatric population. In this narrative review we have summarized the available clinical and pharmacological data, current limitations and future prospects of novel beta lactam antibiotics in the pediatric population.