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Background: In last years the diffusion of carbapenem resistance in Gram-negative bacteria (CR-GNB) is increasing worldwide, mainly due to the expression of carbapenemases. Cefiderocol has molecular characteristics that ideally confers activity against all CR-GNB, but resistant strains have already been identified. We describe cefiderocol susceptibility profile among multi-drug resistant Gram-negative isolated from pediatric patients. Methods: Prospective, single pediatric center study, 1st January 2020–15th June 2023. All GNB carbapenemases producers or phenotypically carbapenem-resistant isolated in the study period were tested for cefiderocol susceptibility. Clinical and microbiological data were collected. A descriptive analysis was performed, comparing the groups of cefiderocol-resistant vs. cefiderocol-susceptible Enterobacterales and non-fermenting Gram-negative bacteria (NF-GNB). Results: Forty-seven GNB were tested for cefiderocol susceptibility; 38% were cefiderocol-resistant: 16/30 (52%) among Enterobacterales and 2/17 (12%) among NF-GNB. None of the patients were previously exposed to cefiderocol. Looking at Enterobacterales, resistance to ceftazidime/avibactam was higher among cefiderocol-resistant vs. cefiderocol-susceptible strains (62% vs 36%, respectively), as MBL expression (67% vs. 36%, respectively). Too few NF-GNB were cefiderocol-resistance to draw any conclusion. No difference in ICU admission and mortality was identified comparing cefiderocol-resistant vs. susceptible strains. Patients colonized/infected by cefiderocol-resistant strains had been previously hospitalized more frequently. Conclusion: In our cohort cefiderocol resistance was mostly registered among Enterobacterales, and especially among MBL producers’ strains (that were alongside resistant to ceftazidime/avibactam). This could be explained by the known possible cross resistance mechanism among ceftazidime/avibactam and cefiderocol. Also, correlation of cefiderocol-resistance with previous hospitalization could be associated with horizontal resistance transmission. Looking at our data, we believe that cefiderocol should be use cautiously, especially empirically and in monotherapy, due to the high resistance rate.

We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus. The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient’s prolonged contact with sewage was initially not mentioned. A literature review of the clinical, imaging, diagnostic, and therapeutic challenges of Whipple disease is also performed.

Abstract 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.

Therapeutic drug monitoring (TDM) is a critical clinical tool used to optimize the safety and effectiveness of drugs by measuring their concentration in biological fluids. These fluids are primarily plasma or blood. TDM, together with real-time dosage adjustment, contributes highly to the successful management of glycopeptide antimicrobial therapies. Understanding pharmacokinetic/pharmacodynamic (PK/PD) properties is vital for optimizing antimicrobial therapies, as the efficacy of these therapies depends on both the exposure of the patient to the drug (PK) and pharmacodynamic (PD) parameters such as the in vitro estimated minimum drug concentration that inhibits bacterial growth (MIC). Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is widely recognized as the gold standard for measuring small molecules, such as antibiotics. This review provides a comprehensive overview of LC-MS/MS methods available for TDM of glycopeptide antibiotics, including vancomycin, teicoplanin, dalbavancin, oritavancin, and telavancin.

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 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 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: 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.

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. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

As there is currently no consensus on managing deep neck infections in pediatric populations, we report a case series from a large pediatric hospital. Clinical data of patients discharged from Istituto Gaslini-Children’s Hospital from January 2014 to June 2020 with peritonsillar, parapharyngeal, or retropharyngeal abscess diagnoses were collected. A total of 59 patients were identified. Patients underwent surgical drainage in 47% of cases. Streptococcus mitis/oralis was the most isolated pathogen. Surgically treated patients did have larger abscesses compared to others, but there were no differences in the duration of hospitalization. Children who received NSAIDs at home had significant delays in diagnosis (median 4 vs. 1.5 days, p = 0.008). In our experience, clinical presentation of DNIs is often evocative, but evaluation should include imaging with CT/MRI. Surgery is effective in larger abscesses, allowing for etiological diagnosis with consequent antibiotic adjusting. From an anamnestic point of view, home medications such as NSAIDs could delay diagnosis.

In recent decades, the Notch pathway has been characterized as a key regulatory signaling of cell-fate decisions evolutionarily conserved in many organisms and different tissues during lifespan. At the same time, many studies suggest a link between alterations of this signaling and tumor genesis or progression. In lymphopoiesis, the Notch pathway plays a fundamental role in the correct differentiation of T and B cells, but its deregulated activity leads to leukemic onset and evolution. Notch and its ligands Delta/Jagged exhibit a pivotal role in the crosstalk between leukemic cells and their environment. This review is focused in particular on Notch2 receptor activity. Members of Notch2 pathway have been reported to be mutated in Chronic Lymphocytic Leukemia (CLL), Splenic Marginal Zone Lymphoma (SMZL) and Nodal Marginal Zone Lymphoma (NMZL). CLL is a B cell malignancy in which leukemic clones establish supportive crosstalk with non-malignant cells of the tumor microenvironment to grow, survive, and resist even the new generation of drugs. SMZL and NMZL are indolent B cell neoplasms distinguished by a distinct pattern of dissemination. In SMZL leukemic cells affect mainly the spleen, bone marrow, and peripheral blood, while NMZL has a leading nodal distribution. Since Notch2 is involved in the commitment of leukemic cells to the marginal zone as a major regulator of B cell physiological differentiation, it is predominantly affected by the molecular lesions found in both SMZL and NMZL. In light of these findings, a better understanding of the Notch receptor family pathogenic role, in particular Notch2, is desirable because it is still incomplete, not only in the physiological development of B lymphocytes but also in leukemia progression and resistance. Several therapeutic strategies capable of interfering with Notch signaling, such as monoclonal antibodies, enzyme or complex inhibitors, are being analyzed. To avoid the unwanted multiple “on target” toxicity encountered during the systemic inhibition of Notch signaling, the study of an appropriate pharmaceutical formulation is a pressing need. This is why, to date, there are still no Notch-targeted therapies approved. An accurate analysis of the Notch pathway could be useful to drive the discovery of new therapeutic targets and the development of more effective therapies.

Rotavirus is a major cause of acute gastroenteritis in children under 5 years of age, with severe illness occurring in 30–40% of cases. In Italian region of Liguria, vaccination with a two-dose human attenuated vaccine was introduced in 2013. We conducted a retrospective study to assess the impact of rotavirus vaccine on hospitalizations for rotavirus-related gastroenteritis (RVGE) at the IRCCS Istituto Giannina Gaslini. Every hospitalization due to laboratory-confirmed RVGE and acute gastroenteritis of unknown origin (AGUO) in patients aged 0–14 years in the period 2008–2019 were anonymously extracted. Vaccine coverage were obtained from the regional vaccination registry. The results were divided in 2008–2012 (before RV vaccine) and 2013–2019 (after) periods. From 2008 to 2012, there was a continuous reduction of AGUO hospitalizations while RVGE increased. Since 2013, a reduction in hospitalization rate was observed for RVGE with a sharp decrease from 17.81 per 10.000 children in 2012 to 0.79 per 10,000 in 2019, parallel with the ascending values of RV vaccination coverage that increased from 36.3% in 2013 to 63.9% in 2019. A significant negative correlation was found between the proportions of vaccinated newborns and RVGE rates (p = .012). Intussusception-related hospitalization did not show substantial modifications. We confirm vaccination as a safe practice that has a significant impact in pediatric hospitalization rates.

Offshore Oil&Gas fluid production installations may be the target of intentional malicious acts (security attacks) carried out by adversaries of different nature and different motivations which may generate major events with severe consequences on workers, the environment and the property. The current study reviews the state of the art concerning the security of Offshore Oil&Gas operations, which is typically addressed according to best practices and qualitative or semi-quantitative methods. However, systematic approaches or guidelines in support of the analysis are still lacking. The current study investigates the possibility of using Adversary Sequence Diagrams (ASDs) as Security Vulnerability/Risk Assessment (SVA/SRA) supporting tools. A case study addressing a fixed Offshore Oil&Gas fluid production platform proved the ability of ASDs to provide credible attack modes within the Physical Protection System (PPS) that the adversaries have to perform in order to accomplish their objectives, as well as the security barriers that can potentially be effective in delaying and detecting the attacks, which are information required by SVA/SRA studies.

Cartilage-hair hypoplasia (CHH) is a syndromic immunodeficiency characterized by metaphyseal dysplasia, cancer predisposition, and varying degrees of anemia. It may present as severe combined immunodeficiency in infancy, or slowly progress until fully manifesting in late adolescence/adulthood. No targeted treatment is currently available, and patients are usually managed with supportive measures, or are offered a bone marrow transplant if the clinical phenotype is severe and a suitable donor is available. We report the case of a young girl presenting with transfusion-dependent erythropoietic failure and immunological features resembling autoimmune lymphoproliferative syndrome who responded well to empirical sirolimus. She later developed a marked growth delay, which was ultimately attributed to metaphyseal dysplasia. A diagnosis of CHH was reached through whole-genome sequencing (WGS), after a less sensitive genetic diagnostic strategy failed. The patient eventually underwent a haploidentical bone marrow transplant due to progressive combined immunodeficiency manifested as cryptococcal meningoencephalitis. This case illustrates the potential role of sirolimus in correcting anemia and partially controlling the immune aberrations associated with CHH, and serves as a reminder of the invaluable role of WGS in diagnosing patients with complex and atypical presentations.

The indoleamine 2,3-dioxygenase 1 (IDO1) metabolic circuitry, comprising the first tryptophan (Trp) catabolite L-kynurenine (Kyn) and the aryl hydrocarbon receptor (AHR), has emerged as a mechanism of cancer immune evasion. Here, we investigated the functional role of the IDO1/Kyn/AHR axis in chronic lymphocytic leukemia (CLL). Our data show that CLL cells expressed an active form of the IDO1 enzyme and microenvironmental stimuli can positively modulate its expression. Interferon (IFN)-γ induces IDO1 expression through the Jak/STAT1 pathway and mediates Kyn production concomitantly with Trp consumption in CLL-conditioned media, while INCB018424 (ruxolitinib), a JAK1/2 inhibitor, impaired both effects. To characterize the involvement of IDO1 in leukemic cell maintenance, we overexpressed IDO1 by vector transfection measuring enhanced resistance to spontaneous apoptosis. IDO1 pro-survival influence was confirmed by treating CLL cells with Kyn, which mediated the increase of induced myeloid leukemia cell differentiation protein (MCL1). Conversely, AHR silencing or its blockade via CH-223191 improved the apoptosis of leukemic clones and mitigated MCL1 expression. Moreover, Kyn-treated CLL cells are less affected by the pro-apoptotic effect of ABT-199 (venetoclax), while CH-223191 showed synergistic/additive cytotoxicity with this drug. Lastly, targeting directly MCL1 in CLL cells with AMG-176, we abrogate the pro-survival effect of Kyn. In conclusion, our data identify IDO1/Kyn/AHR signaling as a new therapeutic target for CLL, describing for the first time its role in CLL pathobiology.

Matteo Bassetti,1,2 Maddalena Peghin,1 Alessio Mesini,3 Elio Castagnola3 1Infectious Diseases Clinic, Department of Medicine University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy; 2Department of Health Sciences, University of Genoa, Genoa, Italy; 3Division of Infectious Diseases, IRCCS Istituto Giannina Gaslini, Genoa, ItalyCorrespondence: Matteo BassettiClinica Malattie Infettive, Azienda Ospedaliera Universitaria Santa Maria Della Misericordia, Piazzale Santa Maria Della Misericordia 15, Udine 33100, ItalyTel +39 0432 559355Fax +39 0432 559360Email matteo.bassetti@asuiud.sanita.fvg.itAbstract: Antimicrobial resistance poses a substantial threat to global public health. The pursuit of new antibiotics has decreased and very few options have been investigated for the treatment of complicated multidrug-resistant Gram-negative (MDR-GN) infections in adult population and even less in pediatric patients. Ceftazidime-avibactam (CAZ-AVI) is novel cephalosporin/β-lactamase inhibitor (BL-BLI) combination with broad antibacterial spectrum. The aim of this review is to describe the current and future role CAZ-AVI in the pediatric population with suspected or confirmed MDR-GN infections.Keywords: pediatric, infections, multidrug-resistant Gram-negative, ceftazidime/avibactam

Chronic lymphocytic leukemia (CLL) has experienced a clinical revolution—thanks to the discovery of crucial pathogenic mechanisms. CLL is still an incurable disease due to intrinsic or acquired resistance of the leukemic clone. Venetoclax is a Bcl-2 inhibitor with a marked activity in CLL, but emerging patterns of resistance are being described. We hypothesize that intrinsic features of CLL cells may contribute to drive mechanisms of resistance to venetoclax. We analyzed the expression of Interferon Regulatory Factor 4 (IRF4), Notch2, and Mcl-1 in a cohort of CLL patients. We evaluated CLL cell viability after genetic and pharmaceutical modulation of Notch2 expression in patients harboring trisomy 12. We tested venetoclax in trisomy 12 CLL cells either silenced or not for Notch2 expression or in combination with an inhibitor of Mcl-1, AMG-176. Trisomy 12 CLL cells were characterized by low expression of IRF4 associated with high levels of Notch2 and Mcl-1. Notch2 and Mcl-1 expression determined protection of CLL cells from spontaneous and drug-induced apoptosis. Considering the involvement of Mcl-1 in venetoclax resistance, our data demonstrated a contribution of high levels of Notch2 and Mcl-1 in a reduced response to venetoclax in CLL cells carrying trisomy 12. Furthermore, reduction of Mcl-1 expression by silencing Notch2 or by treatment with AMG-176 was able to restore the response of CLL cells to venetoclax. The expression of Notch2 identifies a subset of CLL patients, mainly harboring trisomy 12, characterized by high levels of Mcl-1. This biological mechanism may compromise an effective response to venetoclax.

Offshore Oil&Gas operations are a key part of the supply of energy in many countries. Worldwide, about a third of the oil is produced offshore and, in Europe, more than 80% of the current Oil&Gas production takes place offshore. Offshore Oil&Gas installations may be the target of malicious acts aiming at causing severe impacts in terms of damage and media coverage, comparable to the outcomes of major accidents originating from safety-related causes. The attractiveness of such installations is linked to the high amount of hazardous substances handled, their socio-political location, and the possibility of obtaining proprietary information important for the business. In the present study, in order to frame a clear picture of the security threats affecting offshore Oil&Gas operations, a database of 2222 security-related incidents occurred in the last 49 years was developed and analysed. Itemized categories used to classify the events by industrial sector, security threats, attack modes, and final scenarios triggered by the malicious acts, were defined and analysed with Exploratory Data Analysis (EDA). Correlations among itemized categories were investigated using Correspondence Analysis (CA). Overall, the results show the concreteness of the security threats to offshore Oil&Gas installations.

Abstract Background The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. Methods A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). Results During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02–1.06, p

Background: Little is known about epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in children. Aim of this study was to describe CPE epidemiology in a tertiary care pediatric hospital in Italy that admits patients coming from geographic areas with high diffusion of CPE. Methods: Prospective evaluation of the proportion and rates per 100,000 hospital discharges (D) or hospitalization-days (HD) of invasive infections due to CPE from 2013 to 2017 and of CPE infections and colonizations from 2014 to 2017. Disease-preventing strategies comprised patients’ screening at admission, pre-emptive contact isolation precautions pending cultures results, and bundles for prevention of healthcare associated infections. Results: From 2013 to 2017 CPE represented 3.5% of all invasive infections due to Enterobacteriaceae, with rates ranging 7.30–14.33 for D and 1.03–2.06 for HD, without major changes over time. On the contrary, overall rates of isolates increased from 83.03 to 191.34 for D and from 12.21 to 28.35 for HD. The intra-hospital diffusion consisted of 2 small outbreaks without invasive diseases in 2014–2015, and sporadic, not epidemiologically-related cases in 2016–2017. Globally, Escherichia coli and Klebsiella pneumoniae represented 64% of identified CPE, while 70% of carbapenemases identified were metallo-beta-lactamases (VIM or NDM), with changes over time. Conclusions: In our center metallo-beta lactamases were the most frequently identified carbapenemases in Enterobacteriaceae and E. coli and K. pneumoniae the most frequently isolated pathogens carrying these enzymes. A proactive management strategy was effective in containing in-hospital spreading. Keywords: Carbapenemase, Enterobacteriaceae, Pediatrics

Antibiotic resistance is an increasing problem, especially in children with urinary tract infections. Rates of drug-specific resistant pathogens were reported, and an easy prediction model to guide the clinical decision-making process for antibiotic treatment was proposed. Data on microbiological isolation from urinoculture, between January 2007–December 2018 at Istituto Gaslini, Italy, in patients aged Enterobacteriales (Escherichia coli and other Enterobacteriales) accounted for 80.4% of all isolates. Amoxicillin-clavulanate (AMC) and cefixime (CFI) Enterobacteriales resistance was 32.8% and 13.7%, respectively, and remained quite stable among the different age groups. On the contrary, resistance to ciprofloxacin (CIP) (overall 9.6%) and cotrimoxazole (SXT) (overall 28%) increased with age. After multivariable analysis, resistance to AMC/CFI could be predicted by the following: sex; age at sampling; department of admission; previous number of bacterial pathogens isolated. Resistance to CIP/SXT could be predicted by the same factors, excluding sex. The models achieved very good calibration but moderate discrimination performance. Specific antibiotic resistance among Enterobacteriales could be predicted using the proposed scoring system to guide empirical antibiotic choice. Further studies are needed to validate this tool.