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INTRODUCTION AND OBJECTIVE: Community-acquired pneumonia (CAP) is one of the most common reasons of prescribing antibiotics for children, often with overuse of broad-spectrum antibiotics. The aim of this study is to describe the antibiotic prescriptions for Italian children with CAP, at the primary care level. STUDY DESIGN: Retrospective cohort study conducted among children 3 months-14 years of age with CAP, enrolled in Pedianet (http://www.pedianet.it) from January 1, 2009 to December 31, 2018. Antibiotic treatment was defined as narrow-spectrum (NS-ABT) if amoxicillin and broad-spectrum (BS-ABT) if amoxicillin/clavulanic acid, cephalosporins or any combination. Crude and adjusted logistic regressions for the odds of receiving NS-ABT were conducted (all episodes of CAP and per patient). A P value

Among fungal infection, mucormycosis is a rare but severe etiology in immunocompromised patients. Lung and sinus are the usual sites; the involvement of blood vessels is also described. The diagnosis is a real challenge, because blood tests (galactomannan, beta-D-glucan) are negative and the only diagnostic tool is usually the biopsy of the affected zone. Aortitis is rare and usually caused by bacterial infection, fungal etiology is unusual and only episodic cases are reported in literature. Medical therapy alone is usually not sufficient and debilitating surgical intervention is required. We report the case of a child affected by B precursor acute lymphoblastic leukemia, presenting a systemic fungal infection complicated by aortitis, probably due to Mucor. The patient developed fever and pneumonia during the Induction phase of chemotherapy. At the beginning, the infection was treated as bacterial and the diagnosis of Mucor infection was possible only after surgical intervention with histological analysis. Medical therapy (antifungal) was not sufficient alone to cure the infection and an urgent surgical intervention was required. This case underlines the challenge in the diagnosis of mucomycosis, that should be suspected in case of prolonged fever during aplasia, not responding to standard antibiotic and antifungal therapies. Mucor infection often require a combined intervention, both medical and surgical to cure the infection.

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was −10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov ( NCT02790996 ). Findings Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference −7% [95% CI −15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). Interpretation In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. Funding EU Seventh Framework Programme for research, technological development and demonstration.

Vancomycin is frequently prescribed in pediatrics, especially in intensive care unit settings, to treat Gram-positive bacterial infections. This work aims to collect the top-cited articles of pediatric and infectious diseases areas to gather the current evidence and gaps of knowledge on the use of vancomycin in these populations. The most relevant journals reported in the “pediatrics” and “infectious diseases” categories of the 2019 edition of Journal Citation Reports were browsed. Articles with more than 30 citations and published over the last three decades were collected. A bibliometric analysis was performed and 115 articles were retrieved. They were published in 21 journals, with a median impact factor of 4.6 (IQR 2.9–5.4). Sixty-eight of them (59.1%) belonged to “infectious diseases” journals. The most relevant topic was “bloodstream/complicated/invasive infections”, followed by “antibiotic resistance/MRSA treatment”. As for population distribution, 27 articles were on children only and 27 on neonates, most of which were from intensive care unit (ICU) settings. The current literature mainly deals with vancomycin as a treatment for severe infections and antibiotic resistance, especially in neonatal ICU settings. Lately, attention to new dosing strategies in the neonatal and pediatric population has become a sensible topic.

BACKGROUND Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4–13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged CONCLUSIONS Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

BackgroundBoth 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.Methods349 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. Admission day NP swabs were analysed by multiplex PCR for 25 targets.ResultsRSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses.ConclusionRSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.

BackgroundThe immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.MethodsOf 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1–3.7) and 6.1 (5.3–7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).ResultsOverall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.ConclusionsAdults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.

Necrotizing enterocolitis (NEC) is an inflammatory disease of the gastrointestinal tract characterized by ischemic necrosis of the intestinal mucosa, mostly affecting premature neonates. Management of NEC includes medical care and surgical approaches, with supportive care and empirical antibiotic therapy recommended to avoid any disease progression. However, there is still no clear evidence-based consensus on empiric antibiotic strategies or surgical timing. This study was aimed to review the available evidence on the effectiveness and safety of different antibiotic regimens for NEC. MEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases were systematically searched through May 31, 2020. Randomized controlled trials (RCTs) and nonrandomized interventions reporting data on predefined outcomes related to NEC treatments were included. Clinical trials were assessed using the criteria and standard methods of the Cochrane risk of bias tool for randomized trials, while the risk of bias in nonrandomized studies of interventions was evaluated using the ROBINS-I tool. The certainty in evidence of each outcome's effects was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Five studies were included in this review, two RCTs and three observational studies, for a total amount of 3,161 patients. One RCT compared the outcomes of parenteral (ampicillin plus gentamicin) and oral (gentamicin) treatment with parenteral only. Three studies (one RCT and two observational) evaluated adding anaerobic coverage to different parenteral regimens. The last observational study compared two different parenteral antibiotic combinations (ampicillin and gentamicin vs. cefotaxime and vancomycin). No antimicrobial regimen has been shown to be superior to ampicillin and gentamicin in decreasing mortality and preventing clinical deterioration in NEC. The use of additional antibiotics providing anaerobic coverage, typically metronidazole, or use of other broad-spectrum regimens as first-line empiric therapy is not supported by the very limited current evidence. Well-conducted, appropriately sized comparative trials are needed to make evidence-based recommendations.· Ampicillin and gentamicin are effective in decreasing mortality and preventing clinical deterioration in NEC.. · Metronidazole could be added in patients with surgical NEC.. · No study with high-quality evidence was found..

Background Acute otitis media (AOM) and pharyngitis are very common infections in children and adolescents. Italy is one of the European countries with the highest rate of antibiotic prescriptions. The aim of this study is to describe first-line treatment approaches for AOM and pharyngitis in primary care settings in Italy over six years, including the prevalence of ‘wait and see’ for AOM, where prescription of antibiotics is delayed 48 h from presentation, and differences in prescribing for pharyngitis when diagnostic tests are used. Methods The study is a secondary data analysis using Pedianet, a database including data at outpatient level from children aged 0–14 in Italy. Prescriptions per antibiotic group, per age group and per calendar year were described as percentages. “Wait and see” approach rate was described for AOM and pharyngitis prescriptions were further grouped according to the diagnostic test performed and test results. Results We identified 120,338 children followed by 125 family pediatricians between January 2010 and December 2015 for a total of 923,780 person-years of follow-up. Among them 30,394 (mean age 44 months) had at least one AOM diagnosis (n = 54,943) and 52,341 (mean age 5 years) had at least one pharyngitis diagnosis (n = 126,098). 82.5% of AOM diagnoses were treated with an antibiotic within 48 h (mainly amoxicillin and amoxicillin/clavulanate) and the “wait and see” approach was adopted only in 17.5% of cases. The trend over time shows an increase in broad spectrum antibiotic prescriptions in the last year (2015). 79,620 (63%) cases of pharyngitis were treated and among GABHS pharyngitis confirmed by rapid test 56% were treated with amoxicillin. The ones not test confirmed were treated mainly with broad spectrum antibiotics. Conclusions Despite guidance to use the ‘wait and see’ approach in the age group analyzed, this strategy is not often used for AOM, as previously noted in other studies in hospital settings. Broad-spectrum antibiotic prescription was more frequent when pharyngitis was not confirmed by rapid test, in keeping with evidence from other studies that diagnostic uncertainty leads to overuse of antibiotics. Electronic supplementary material The online version of this article (10.1186/s13052-019-0696-9) contains supplementary material, which is available to authorized users.

Despite the lack of evidence that bronchodilators, corticosteroids, and antibiotics are useful in treating bronchiolitis, their use is still widespread. This study aimed to determine the consumption of antibiotics for bronchiolitis before and after a procalcitonin-guided clinical pathway (CP) implementation. In December 2019, a CP for lower respiratory tract infection management was implemented at the Department of Women’s and Children’s Health at Padua University Hospital. This was a pre-post, quasi-experimental study that assessed the changes in the treatment of bronchiolitis during two bimesters preceding the CP implementation (pre-period: January 2018–February 2018 and January 2019–February 2019) and during the bimester after CP implementation (post-period January 2020–February 2020). After the CP implementation, there was a significant reduction in antibiotic prescriptions from 36.2% to 12.5% (p = 0.036) in patients hospitalized for bronchiolitis. Co-amoxiclav treatment, the antibiotic most commonly administered, decreased from 66.6% to 33.3%. Among outpatients’ bronchiolitis episodes, a statistically significant decrease in beta2-agonists’ use (from 18.0% to 4.4%, pre and post periods) and a quasi-significant decrease in corticosteroid use (from 8.0% to 0% pre and post periods) were observed. An evidence-based CP supported by educational lectures was associated with significant changes in the physicians’ prescribing habits.

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.

In Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0–24 months before (December 2012–December 2014), in between (December 2014–December 2015) and after (December 2015–December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, β2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications.

Background Although SARS‐CoV‐2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti‐SARS‐CoV‐2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti‐SARS‐CoV‐2 immunity in children with distinct symptomatology. Methods Between March and July 2020, we recruited 15 SARS‐CoV‐2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS‐CoV‐2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti‐SARS‐CoV‐2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen‐specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. Results Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti‐SARS‐CoV‐2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS‐CoV‐2 IgG, levels of neutralizing activity, and frequency of Ag‐specific B and CD8+ T cells, whereas pro‐inflammatory plasma protein profile was found to be associated with symptomatology. Conclusion We demonstrated the development of anti‐SARS‐CoV‐2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.

Aims Compared with adult patients, clinical manifestations of children’s coronavirus disease-2019 (COVID-19) are generally perceived as less severe. The objective of this study was to evaluate cardiac involvement in previously healthy children with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Methods and results We analysed a cohort of 53 paediatric patients (29 males, 55%), mean age 7.5 ± 4.7 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. Thirty-two age, sex, and body surface area comparable healthy subjects were used as control group. Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62.4 ± 4.1% vs. 65.2 ± 5.5%; P = 0.012). Tricuspid annular plane systolic excursion (20.1 ± 3 mm vs. 19.8 ± 3.4 mm; P = 0.822) and left ventricular (LV) global longitudinal strain (−21.9 ± 2.4% vs. −22.6 ± 2.5%; P = 0.208) were comparable between the two groups. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 14 subjects (26%) with a regional peak systolic strain below −16% (−2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings. Conclusion SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.

Background Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient’s age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. Methods A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. Results Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. Conclusions The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

Background To evaluate the ability of Weighted-Incidence Syndromic Combination Antibiograms (WISCA) to inform the selection of empirical antibiotic regimens for suspected paediatric community-acquired urinary tract infections. Methods Data were collected from outpatients ( Results 385 of 620 urine culture requests were included in the model analysis. The most frequently observed bacterium was E. coli (85% and 87%, Centre A and B). No centre effect on coverage estimates was found, and data were successfully pooled together. Coverage ranged from 77.8% (Co-trimoxazole) to 97.6% (Carbapenems). Complex cases and males had significantly lower odds of being covered by a regimen than non-complex cases and females (odds ratio (OR) 0.49 [95% HDI, 0.38–0.65], and OR: 0.73 [95% HDIs, 0.56–0.96] respectively). Children aged 3–5 years had lower odds of being covered by a regimen than other age groups, except for neonates. Conclusions The developed WISCAs provide highly informative estimates on coverage patterns overcoming the limitation of combination antibiograms and expanding the framework of previous Bayesian WISCA algorithm.

In the Veneto Region, an exponential spread of patients affected by 2019 novel Coronavirus disease (COVID-19) has been observed after February 21st. Since then, we have been evaluating children suspected or confirmed for SARS-CoV-2 infection. A protocol for pediatric hospital reorganization and children management has been developed, since the beginning of the epidemic. A pre-triage area has been created at the immediate entrance of the pediatric emergency room, for all uncritical pediatric patients. According to the epidemiologic and clinical risk factors, all children/adolescents have been addressing to one of the four different pathways created. The strict application of this protocol has been leading to quickly identification, isolation, and management of all positive children, preventing SARS-CoV-2 intrahospital spread.

Fusarium species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host’s immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of Fusarium solani infection in a 9-year-old child with acute lymphoblastic leukemia (ALL). This patient presented a deep wound in the elbow at diagnosis. During the induction phase of chemotherapy, he developed multiple skin lesions and severe pneumonia; Fusarium solani was cultured from the skin lesions. He was treated with a high dose of liposomal amphotericin B, followed by voriconazole. Starting from this peculiar case, we collected all patients with acute leukemia affected by Fusarium infection, treated in the pediatric Onco-Hematology Division of Padua University Hospital during the last 20 years. We identified another six cases: all these patients were affected by acute myeloid leukemia (AML) and five of them presented a relapsed/refractory disease. Two out of seven patients died because of infection; five patients recovered from infection, but three out of seven died because of leukemia. Skin lesions in immunocompromised patients should rise the suspicion of disseminated fusariosis. Furthermore, considering the emergence of filamentous fungi in immunocompromised patients, we all should be aware of Fusarium infection, reminding us that the diagnosis is important to cure the infection.

A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.

Objectives SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population. Methods A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included. Results Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population. Conclusion Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.

Background and setting Little is known about SARS-CoV-2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS-CoV-2 cases in PLWHA. Methods A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS-CoV-2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS-CoV-2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes. Results Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS-CoV-2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics. Conclusion It is still unclear if HIV infection may influence SARS-CoV-2 infection and disease course, however some PLWHA and particularly males affected by ARV-related complications may be at greater risk of severe Covid-19 course.

Optimizing the use of antibiotics has become mandatory, particularly for the pediatric population where limited options are currently available. Selecting the dosing strategy may improve overall outcomes and limit the further development of antimicrobial resistance. Time-dependent antibiotics optimize their free concentration above the minimal inhibitory concentration (MIC) when administered by continuous infusion, however evidences from literature are still insufficient to recommend its widespread adoption. The aim of this review is to assess the state-of-the-art of intermittent versus prolonged intravenous administration of antibiotics in children and neonates with bacterial infections. We identified and reviewed relevant literature by searching PubMed, from 1 January 1 2000 to 15 April 2020. We included studies comparing intermittent versus prolonged/continuous antibiotic infusion, among the pediatric population. Nine relevant articles were selected, including RCTs, prospective and retrospective studies focusing on different infusion strategies of vancomycin, piperacillin/tazobactam, ceftazidime, cefepime and meropenem in the pediatric population. Prolonged and continuous infusions of antibiotics showed a greater probability of target attainment as compared to intermittent infusion regimens, with generally good clinical outcomes and safety profiles, however its impact in terms on efficacy, feasibility and toxicity is still open, with few studies led on children and adult data not being fully extendable.

Background Retropharyngeal and parapharyngeal abscesses (RPAs, PPAs) usually affect young children. Surgical drainage and/or antibiotic therapy are treatment of choice, but no specific guidelines exist. In order to reduce the risk of severe complications, appropriate diagnosis and therapy are necessary. The aims of the study were to review diagnosis and management of children with RPAs/PPAs and to compare surgical versus medical approach. Methods This is a multicenter retrospective study including all patients younger than 15 years admitted at 4 Italian pediatric hospitals of Florence, Padua, Rome, and Treviso, with International Classification of Diseases, Ninth Revision discharge diagnosis code of RPAs and PPAs, from January 1, 2008, to December 31, 2016. Results One hundred fifty-three children were included. The median age was 4.4 years, with overall male predominance. Heterogeneous signs and symptoms (fever, neck cervical, lymphadenopathy, pain, and stiff neck most frequently) and a large mixture of bacteria from pus cultures were detected. Computer tomography (66.7%) and magnetic resonance imaging (27.5%) were performed to confirm the presence of abscess. Fifty-one percent of abscesses were greater than 3 cm. Eighty-seven patients (56.9%) underwent surgery, and 66 (43.1%) were treated with antibiotics alone (mostly ceftriaxone, metronidazole, amikacin, and clindamycin) with median days of therapy of 26.5 days and length of therapy of 16.0 days of median. Median length of stay was 11 days. None had severe complications. Multivariate analysis indicated as independent predictive factors of surgery abscess of 3 cm or greater, high white blood cell count, and-most of all-the hospital of admission. Conclusions Deep neck abscesses mostly affect patients in early childhood, with a combination of nonspecific signs and symptoms, and it still emerges as a heterogeneous approach in diagnosis and management of these infections. Thus, common shared protocols represent an essential tool in order to standardize care and improve patients' outcomes.

Acute osteomyelitis still represents a significant clinical challenge, with an increasing incidence in paediatric population. A careful assessment and a rapid diagnosis with proper timing and choice of empirical antimicrobial therapy are necessary to avoid sequelae. The initial treatment should consist of empirical antibiotic therapy, to cover the major responsible pathogens in each age group. We made a literature search with PubMed and Cochrane database from 2000 to 2019 in English, French, and Spanish languages using the key words “osteomyelitis, children, clinical, diagnosis, and treatment”. The child’s clinical features, age, and the microbiological profile of the geographic area should be evaluated for diagnosis and in the choice of antibiotic treatment. Latest data suggest the administration of intravenous antibiotics for a short period, with subsequent oral therapy, according to the improvement of clinical status and inflammatory markers. For children older than 3 months, the shift to oral medications is already possible after a short course of intravenous therapy, until recovery. The timing for the shift from cefazolin to cephalexin or cefuroxime, intravenous clindamycin to oral clindamycin, and intravenous ceftriaxone + oxacillin to oral equivalents will be decided according to the improvement of clinical status and inflammatory markers. We also present the approach to osteomyelitis due to difficult pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL)-positive S. aureus infections. In this review, we present the current approach to the clinical diagnosis and management of osteomyelitis in childhood, with an update on recent recommendations, as a useful instrument to understand the rationale of antibiotic therapy.

Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women’s and Children’s Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new “double-gate approach”: a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known:• WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January.• SARS-CoV-2 testing was made available across Europe in February.What is New:• Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage.• A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources.

Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.

Fluconazole prophylaxis (FP) for invasive candidiasis (IC) in preterm newborns is still a debated topic. In this review, we describe the most important papers on the topic, and we discuss pros and cons of the use FP in newborns according to these paper’s findings. Since 2001, several studies have been published on the use of FP to prevent IC. While most of them agree on the effectiveness of FP in reducing IC, especially in NICUs with high IC rates, the lack of evidence of decrease in overall mortality, and the risks associated with fluconazole administration both concerning neurodevelopmental impairment and the increase in Candida resistances still pose great concern against the universal implementation of FP. A local risk-based selection strategy could represent the best choice to optimize the benefits of FP and minimize the potential long-term toxicity and the development of resistant pathogens.

Antimicrobial prescriptions in neonatal intensive care units (NICUs) represent a point of concern for the emergence of MDROs and for morbidity associated with prolonged antibiotic exposure (e.g., invasive candidiasis, necrotizing enterocolitis, and late-onset sepsis). Antimicrobial stewardship programs (ASPs) have shown to be a valuable tool for the prevention of resistance with the goals of optimizing clinical outcomes while decreasing unnecessary prescribing. The most frequent ASP strategies include the correct collection and interpretation of microbiological specimens, prescription of the narrowest-spectrum antibiotic appropriate for a particular case, and de-escalation or discontinuation of therapy in defined situations. A robust ASP requires everyday multidisciplinary collaboration between ID physicians, neonatologist, clinical pharmacists, clinical microbiologists, infection control professionals, hospital epidemiologists, and information services specialists. Education and clinical pathways (e.g., sepsis or surgical prophylaxis pathways) are an excellent starting point if followed by proactive interventions such as prospective audits and feedback and formulary restriction with prior antimicrobial authorization. The current review outlines the problems faced in NICU antimicrobial prescribing and presents various solutions from the literature.

Background. Pneumonia represents an important threat to children’s health in both developed and developing countries. In the last 10 years, many national and international guidelines on the treatment of pediatric CAP have been published, in order to optimize the prescription of antibiotics and limit their cost and side effects. However, the practical implementation of these guidelines is still limited.Main Text. We analyzed the current recommendations for the therapy of pediatric community-acquired pneumonia (CAP) that all converge on the identification of aminopenicillins and beta-lactams as the optimal treatment for CAP. We also conducted a review of the current literature on antibiotic regimens used for pediatric CAP to identify the current state of guidelines implementation in different settings. We selected 37 studies published from 2010 to 2016, including both retrospective and prospective studies, mainly cross-sectional and hospital based. The results show a global heterogeneity in the antibiotics prescription for pediatric CAP, with application of guidelines varying from 0% to more than 91% and with important differences even within the same country.Conclusions. Our review has demonstrated that the implementation of the guidelines is still limited but also that achieving the optimal prescription is possible and can be done in both developed and developing countries.

The original article [1] contains an error in Fig. 1 whereby the number of selected articles of the first box is incorrect.

Introduction Acute otitis media (AOM) is the most common childhood disease leading to antibiotic use. More than 80% of children under three years of age experience at least one episode, and about one-third of these report significant recurrence of episodes. In recent years, several studies reported that normal nasopharyngeal flora inhibits growth of common otopathogens, suggesting that maintenance of an “adequate” nasopharyngeal flora might prevent occurrence of upper respiratory tract infections, including AOM. This study aims to determine whether five-month treatment with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray prevents recurrence of AOM and prescription of antibiotics in children with diagnosis of recurrent AOM. Methods Observational prospective cohort study including children aged 1–6 years with diagnosis of recurrent AOM registered with 31 Italian family pediatricians. 81 children were enrolled in the study from September 2016 to the end of the five therapeutic cycles of the Streptococcus salivarius 24SMB and Streptococcus oralis 89a supplied 7 days each month for 5 consecutive months. For each treated child, one untreated control was randomly selected, 1:1 matched for gender, age, and follow-up. Results 158 children (79 treated and 70 untreated) were included into the analysis (mean age, 3.9 years; 47% female). Univariate analysis showed a statistically significant 34% (95% CI 1%–56%) reduction in number of AOM episodes in treated children compared with those not treated. Significantly fewer antibiotics were dispensed among treated children (24%, 95% CI 1%–41%). Conclusions Our findings suggest that intermittent treatment of children with diagnosis of recurrent AOM with nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a for a period of five months might be effective in preventing antibiotic use associated with recurrent episodes of AOM. Additional larger studies to address this important clinical problem are recommended.

BackgroundAntibiotics are the most common medicines prescribed to children in hospitals and the community, with a high proportion of potentially inappropriate use. Antibiotic misuse increases the risk of toxicity, raises healthcare costs, and selection of resistance. The primary aim of this systematic review is to summarize the current state of evidence of the implementation and outcomes of pediatric antimicrobial stewardship programs (ASPs) globally.MethodsMEDLINE, Embase and Cochrane Library databases were systematically searched to identify studies reporting on ASP in children aged 0–18 years and conducted in outpatient or in-hospital settings. Three investigators independently reviewed identified articles for inclusion and extracted relevant data.ResultsOf the 41,916 studies screened, 113 were eligible for inclusion in this study. Most of the studies originated in the USA (52.2%), while a minority were conducted in Europe (24.7%) or Asia (17.7%). Seventy-four (65.5%) studies used a before-and-after design, and sixteen (14.1%) were randomized trials. The majority (81.4%) described in-hospital ASPs with half of interventions in mixed pediatric wards and ten (8.8%) in emergency departments. Only sixteen (14.1%) studies focused on the costs of ASPs. Almost all the studies (79.6%) showed a significant reduction in inappropriate prescriptions. Compliance after ASP implementation increased. Sixteen of the included studies quantified cost savings related to the intervention with most of the decreases due to lower rates of drug administration. Seven studies showed an increased susceptibility of the bacteria analysed with a decrease in extended spectrum beta-lactamase producersE. coliandK. pneumoniae;a reduction in the rate ofP. aeruginosacarbapenem resistance subsequent to an observed reduction in the rate of antimicrobial days of therapy; and, in two studies set in outpatient setting, an increase in erythromycin-sensitiveS. pyogenesfollowing a reduction in the use of macrolides.ConclusionsPediatric ASPs have a significant impact on the reduction of targeted and empiric antibiotic use, healthcare costs, and antimicrobial resistance in both inpatient and outpatient settings. Pediatric ASPs are now widely implemented in the USA, but considerable further adaptation is required to facilitate their uptake in Europe, Asia, Latin America and Africa.

The optimal standard of care for carbapenem-resistant bloodstream infections in children is currently unknown. This systematic review, aiming to define the best available treatments to be compared with new antibiotics in clinical trials, clearly points out the paucity of available data. The simplification and a wider harmonization of study design are a global priority to inform the best strategies to treat these life-threatening infections in children.

Daily assumption of antiretroviral drugs and HIV-related immune activation lead to important side effects, which are particularly evident in vertically infected patients. Bone homeostasis impairment and reduction of bone mineral density (BMD) is one of the most important side effects. Primary aim of this study is to assess the prevalence of bone homeostasis alterations in a group of vertically infected patients; secondary aim is to analyze the relationship between bone homeostasis alterations and anthropometric data, severity of HIV infection, and antiretroviral therapy. We studied 67 patients with vertically transmitted HIV-1 (aged 6-31 years), followed by the Pediatric Infectious Disease Unit of the University Hospital of Padua, Italy. We analyzed bone turnover markers (P1NP and CTx) and we performed lumbar spine and femoral dual energy X-ray absorption densitometry (DXA). Personal and anthropometric data and information on HIV-infection severity and antiretroviral therapy were collected for all patients. We found that BMD values recorded by DXA showed a significant correlation with age, race, BMI, physical activity, and antiretroviral therapy duration. P1NP was increased in 43% of patients, while CTX in 61% of them. P1NP alteration was related to age, race, BMI, physical activity, therapy duration, and ever use of protease inhibitors and nucleotide reverse transcriptase inhibitors. CTX alteration was found to be correlated only with age. In conclusion, our study confirms that a wide percentage of HIV vertically infected patients show reduced BMD and impaired bone homeostasis. Strict monitoring is needed in order to early identify and treat these conditions.

Purpose This study aims to determine the effectiveness of an Antimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP). Materials and methods This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation), in a tertiary Pediatric Surgical Centre. All patients from 1 month to 15 years of age receiving one or more surgical procedures were eligible for inclusion. PAP was defined appropriate according to clinical practice guidelines. Results Seven hundred sixty-six children were included in the study, 394 in pre-intervention and 372 in post-intervention. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (p = 0.02) and combination therapy (p = 0.004). Even the duration of prophylaxis decreased during the post-intervention period, with an increase of correct PAP discontinuation from 45.1 to 66.7% (p