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Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies. [ABSTRACT FROM AUTHOR]

Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment for SARS-CoV-2 infection in children aged from 24 days to 18 years old. [ABSTRACT FROM AUTHOR]

Objective and Design: Risk factors for severe measles are poorly investigated in high-income countries. The Italian Society for Paediatric Infectious Diseases conducted a retrospective study in children hospitalised for measles from January 2016 to August 2017 to investigate the risk factors for severe outcome defined by the presence of long-lasting sequelae, need of intensive care or death.Results: Nineteen hospitals enrolled 249 children (median age 14.5 months): 207 (83%) children developed a complication and 3 (1%) died. Neutropaenia was more commonly reported in children with B3-genotype compared with other genotypes (29.5% vs 7.7%, p=0.01). Pancreatitis (adjusted OR [aOR] 9.19, p=0.01) and encephalitis (aOR 7.02, p=0.04) were related to severe outcome in multivariable analysis, as well as C reactive protein (CRP) (aOR 1.1, p=0.028), the increase of which predicted severe outcome (area under the receiver operating characteristic curve 0.67, 95% CI 0.52 to 0.82). CRP values >2 mg/dL were related to higher risk of complications (OR 2.0, 95% CI 1.15 to 3.7, p=0.01) or severe outcome (OR 4.13, 95% CI 1.43 to 11.8, p<0.01).Conclusion: The risk of severe outcome in measles is independent of age and underlying conditions, but is related to the development of organ complications and may be predicted by CRP value. [ABSTRACT FROM AUTHOR]

Background Measles is a highly communicable infection with potentially severe complications. It is rarely reported in high-income countries and the limited awareness and experience of pediatricians may result in misdiagnosis. The present study aimed at investigating physician's ability and timing to reach diagnosis during a recent outbreak in Italy. Methods The Italian Society for Pediatric Infectious Diseases conducted a retrospective, multicenter study in children hospitalized for measles between 1 January 2016 and 30 August 2017 in secondary and tertiary care hospitals. The appropriateness of diagnosis at admission, the time to reach clinical diagnosis, and serological confirmation of measles were recorded. Results At hospital admission, measles was misdiagnosed in 101 (40.5%) of the 249 children (median age, 14.5 months) enrolled. The appropriate diagnosis increased from 30% to 72.5% during the period of observation (P <.001). A greater chance of receiving an appropriate diagnosis was demonstrated in children who reported a contact with measles (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.0–9.2) or in those seen in institutions that managed more cases (OR, 7.39; 95% CI, 3.22–16.9; P =.0001). In contrast, children with underlying chronic conditions had a higher risk of misdiagnosis (appropriate diagnosis OR, 0.19; 95% CI, 0.10–0.33). The mean time from the onset of symptoms to clinical diagnosis was 4.55 ± 2.2 days and to serological confirmation was 7.0 ± 3.4 days. Conclusions Measles is frequently misdiagnosed in low-prevalence settings. Specific measures to increase pediatricians' awareness about vaccine-preventable infections need to be implemented. [ABSTRACT FROM AUTHOR]

Background: Acute/subacute haematogenous osteomyelitis (AHOM/SAHOM) are potentially devastating diseases. Updated information about the epidemiology, management and outcome of AHOM/SAHOM is needed to minimize the risk of complications and sequelae.Methods: A multicenter study was performed to evaluate retrospectively the management and outcome of AHOM/SAHOM in Italy. Data from children aged >1 month, and hospitalized between 2010 and 2016, in 19 pediatric centers, were analyzed.Results: 300 children with AHOM and 98 with SAHOM were included. Median age was 6.0 years (IQR: 2.0-11.0). No clinical difference was observed with the exception of fever at onset (63.0% vs. 42.9%; P < 0.0001), and a more common spinal involvement in SAHOM (6.7% vs 20.4%; P < 0.001). Fifty-Eight Staphylococcus aureus strains were isolated; 5 (8.6%) were MRSA. No Kingella kingae infection was documented. No different risk for complication/sequela was observed between AHOM and SAHOM (38.3% vs. 34.7%; OR:0.85; 95%CI: 0.53-1.38; P = 0.518). Duration and type of antibiotic therapy were not associated with risk of complication/sequelae.Conclusion: AHOM and SAHOM displayed some differences, however occurrence and risk factors for complications and sequelae are similar, and the same empiric treatment might be recommended. [ABSTRACT FROM AUTHOR]

Background: Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome. Methods: A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe. Results: A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids. Conclusions: We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome. [ABSTRACT FROM AUTHOR]

Even if varicella is generally considered a harmless disease in childhood, severe complications may occur. We examined varicella skin complications (VSCs) in hospitalized immunologically healthy children, over a nine-year period. We also systematically analyzed previous reports to calculate the rate of VSCs in the literature. VSCs occurred in 16.4% of children hospitalized for varicella. This figure is in accordance with the literature, as the range of VSCs was 2.6%-41.2%. Skin complications may represent determinants of hospitalization and of other indirect costs in young children. [ABSTRACT FROM AUTHOR]

Objective: The Italian Society for Pediatric Infectious Diseases created a registry on children with infective endocarditis (IE) hospitalized in Italy.Methods: A cross-sectional survey was conducted on patients hospitalized due to IE in Italian paediatric wards between January 1, 2000, and June 30, 2015.Results: Over the 15-year study period, 47 IE episodes were observed (19 males; age range, 2-17 years). Viridans Streptococci were the most common pathogens among patients with predisposing cardiac conditions and Staphylococcus aureus among those without (37.9% vs. 5.5%, p = 0.018, and 6.9% vs. 27.8%, p = 0.089, respectively). Six of the 7 (85.7%) S. aureus strains were methicillin-resistant. The majority of patients with and without predisposing cardiac conditions recovered without any complications.Conclusion: In Italy, paediatric IE develops without any previous predisposing factors in a number of children, methicillin-resistant S. aureus has emerged as a common causative agent and the therapeutic approach is extremely variable. [ABSTRACT FROM AUTHOR]

Abstract: We explored complications and risk factors for severe disease in 78 children with swine influenza admitted to Bambino Gesù Children Hospital. The majority of our children experienced respiratory complications (55%). Previously healthy children developed a chest consolidation more frequently than chronic diseases affected patients (p =0.04). Apparently, the incidence of respiratory complications was slightly higher in the neutropenic group than in those with a normal value of neutrophilis (respectively 94.1% and 80%). [Copyright &y& Elsevier]

Background Human cytomegalovirus (CMV) is the main cause of congenital viral infection. There are not early and certain prognostic markers to define infection /disease course and no standard treatment of children with symptomatic congenital infection is available as yet. Indeed, a small number of infants present severe neurological complications and isolated visual and hearing impairments. The aim of our study is to verify possible correlations between immunologic alterations and clinical/ therapeutic aspects. Eighteen eligible infants were enrolled in our study. Eight of them were symptomatic, showing neurological alterations. Methods Lymphocyte proliferation was detected by co-culture with mitogens (Phytohemagglutinin and Pokeweed), anti-CD3 monoclonal antibody, recall (Candida) and CMVspecific antigens. T-cell receptor (TCR) repertoire of CD8+ and CD4+ T-cell subsets was analysed by Spectratyping after RNA extraction and cDNA synthesis and amplification with a SuperScript One-Step RT-PCR kit (Invitrogen) by 24 different Vβ primers combination with a 3' Cβ labelled primer. IFN-γ production after CMV lisate and peptides pool stimulation was evaluated by cellELISA in 384 wells microplates. Results Standard immunological investigations as immunoglobulins levels and cellular immunity did not show any alteration in both groups. All symptomatic patients (8/8) did not show any specific CMV response in lymphoproliferative assay. Six out of ten asymptomatic patients showed a good CMV specific response (Stimulation Index > 3). TCR spectratyping analysis on CD8 T-cell subset showed a various degree of alteration in all symptomatic patients and in six out of nine analysed asymptomatic patients. CellELISA assay on CD4 and CD8 T-cell subset was performed and the evaluation of results is ongoing. Conclusions Our preliminary data suggest a possible correlation between a lack of CMV specific response and higher degree alteration of TCR spectratyping analysis in symptomatic versus asymptomatic patients. [ABSTRACT FROM AUTHOR]

Abstract: A child referred to Infectious Disease Unit for varicella complicated by pneumonia with pleural effusion. Due to not improvement, laboratory search was extended to uncommon pathogens, revealing Nocardia transvalensis infection. It is likely that varicella induced immunodepression, facilitating opportunistic infection in an otherwise healthy and immunocompetent child. To our knowledge, our report is the first case of Nocardia infection in varicella. [Copyright &y& Elsevier]

Abstract: Although varicella has usually an uncomplicated course in early childhood, several neurological complications may occur. We conducted a study to review the type and the rate of varicella neurological complications in a case series of hospitalized immunologically healthy children over nearly a 8 year period. We also systematically reviewed data from the literature to estimate the rate of varicella neurological complications. In our case reports, the proportion of neurological complications among all those hospitalized for varicella was of 21.7% (CI 17.9–26%). The pooled prevalence of neurological complications resulting from the systematic review of the literature identifies the likelihood of such complications in the range of 13.9–20.4%. Although neurological complications of chickenpox do not frequently result in permanent sequelae, they represent significant determinants of prolonged hospital stay and of other indirect costs. The obtained results may be useful for estimating costs associated with hospitalization from varicella in cost–benefit analysis for immunization. [Copyright &y& Elsevier]

Background: Laparoscopic appendectomy followed by postoperative intravenous (IV) antibiotics is the standard of care for acute appendicitis and postoperative prevention of intra-abdominal abscesses. The aim of or study was to determine if intraperitoneal irrigation with antibiotics could help prevent intra-abdominal abscess formation after laparoscopic appendectomy for complicated appendicitis in pediatric patients., Methods: A retrospective study was conducted on consecutive pediatric patients with acute appendicitis who had appendectomy in our Pediatric Surgery Department between August 2020 and February 2022. We compared two groups with similar age and symptoms. The first group (A) was treated with the normal standard of care, i.e., laparoscopic appendectomy and postoperative IV antibiotic therapy. For the second group (B) intraperitoneal cefazoline irrigation was added at the end of the laparoscopic procedure. Postoperative intra-abdominal abscess was diagnosed with ultrasound examination, performed after clinical suspicion/abnormal blood test results., Results: One hundred sixty patients (males:females 109:51; median age 10.5 years [range 3-17 years]) who had laparosopic appendectomy for complicated appendicitis were included, 82 in group A and 78 in group B. In the first 7 days after surgery, 18 patients in group and 5 in group B developed an intra-abdominal abscess (p < 0.005). Drains were positioned in 38 patients in group A vs. 9 in group B. One patient in group A had a different complication which was infection of the surgical incision., Conclusions: Intraperitoneal cefazoline irrigation at the end of the laparoscopic appendectomy in pediatric patients significantly reduces the formation of intra-abdominal abscesses.

Background and Objectives: Most cases of spondylodiscitis in children aged between 6 and 48 months old could be caused primarily by K. kingae. The present prospective study aimed to determine whether an innovative and indirect diagnosis approach - based on detection of K. kingae DNA in the oropharynx of children with suspected spondylodiscitis - provides sufficient evidence that this microorganism is responsible for the infection., Methods: We prospectively analysed infants admitted for spondylodiscitis, considering above all the results of PCR realized in oropharyngeal swabs and in blood samples., Results: Four of the 29 performed K. kingae-specific real-time PCR assay in blood were positive (13.8%), whereas 28 of the 32 K. kingae-specific real-time PCR assay realized on throat swabs were positive (87.5%)., Conclusions: This study demonstrates that performing oropharyngeal swab PCR is able to detect K. kingae in almost 90% of the toddlers with confirmed spondylodiscitis. That provides strong arguments for the hypothesis that K. kingae should be considered as the main aetiological pathogen to suspect in children between 6 and 48 months old with spondylodiscitis. Finally, it seems to us reasonable that oropharyngeal swab may become an early decision-making tool for the indirect identification of K. kingae in spondylodiscitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Chargui, Krzysztofiak, Bernaschi, De Marco, Coulin, Steiger, Dayer and Ceroni.)

Objectives: The aim of this study is to provide new data on pediatrics spondylodiscitis for an optimal clinical management of this site-specific osteomyelitis. Methods: We reported 48 cases of pediatric spondylodiscitis and made three comparisons between: (1) tubercular and non-tubercular cases; (2) patients aged more or less than 5 years; (3) children with spondylodiscitis and 62 controls with non-vertebral osteomyelitis. Results: A higher rate of sequelae was reported in patients with tubercular spondylodiscitis, but no significant differences were noted at the cut-off of 5 years of age. Compared to non-vertebral osteomyelitis, pediatric spondylodiscitis affects younger children of both genders, usually presenting with afebrile back pain, and requiring longer time to admission, hospitalization, and antibiotic therapy. Conclusion: Pediatric spondylodiscitis is an insidious disease with a non-specific presentation in childhood and peculiarities of its own. However, when clinical remission is obtained by an early start of broad-spectrum antibiotics, prolonging the therapy does not improve, nor worsens, the outcome. Surgical management is mandatory in case of vertebral instability and neurological signs but can be avoided when the infection is promptly treated with antibiotic therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Roversi, Mirra, Musolino, Barbuti, Lancella, Deriu, Iorio, Villani, Crostelli, Mazza and Krzysztofiak.)

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission ( p < 0.01) and linearly to length of stay ( p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications ( p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission ( p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garazzino, Lo Vecchio, Pierantoni, Calò Carducci, Marchetti, Meini, Castagnola, Vergine, Donà, Bosis, Dodi, Venturini, Felici, Giacchero, Denina, Pierri, Nicolini, Montagnani, Krzysztofiak, Bianchini, Marabotto, Tovo, Pruccoli, Lanari, Villani, Castelli Gattinara and the Italian SITIP-SIP Pediatric Infection Study Group.)

Background: Measles is a highly communicable infection with potentially severe complications. It is rarely reported in high-income countries and the limited awareness and experience of pediatricians may result in misdiagnosis. The present study aimed at investigating physician's ability and timing to reach diagnosis during a recent outbreak in Italy., Methods: The Italian Society for Pediatric Infectious Diseases conducted a retrospective, multicenter study in children hospitalized for measles between 1 January 2016 and 30 August 2017 in secondary and tertiary care hospitals. The appropriateness of diagnosis at admission, the time to reach clinical diagnosis, and serological confirmation of measles were recorded., Results: At hospital admission, measles was misdiagnosed in 101 (40.5%) of the 249 children (median age, 14.5 months) enrolled. The appropriate diagnosis increased from 30% to 72.5% during the period of observation (P < .001). A greater chance of receiving an appropriate diagnosis was demonstrated in children who reported a contact with measles (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.0-9.2) or in those seen in institutions that managed more cases (OR, 7.39; 95% CI, 3.22-16.9; P = .0001). In contrast, children with underlying chronic conditions had a higher risk of misdiagnosis (appropriate diagnosis OR, 0.19; 95% CI, 0.10-0.33). The mean time from the onset of symptoms to clinical diagnosis was 4.55 ± 2.2 days and to serological confirmation was 7.0 ± 3.4 days., Conclusions: Measles is frequently misdiagnosed in low-prevalence settings. Specific measures to increase pediatricians' awareness about vaccine-preventable infections need to be implemented., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.

Data on daptomycin use in the pediatric setting are scanty. We conducted a multicenter, retrospective study on 46 children treated with intravenous daptomycin at a mean dosage of 7.0 mg/kg/d, for a median of 14 days. Three children had adverse events possibly related to daptomycin. The drug was overall well tolerated, even with prolonged treatment.