Recommendations for the diagnosis of pediatric tuberculosis.

Tuberculosis (TB) is still the world's second most frequent cause of death due to infectious diseases after HIV infection, and this has aroused greater interest in identifying and managing exposed subjects, whether they are simply infected or have developed one of the clinical variants of the disease. Unfortunately, not even the latest laboratory techniques are always successful in identifying affected children because they are more likely to have negative cultures and tuberculin skin test results, equivocal chest X-ray findings, and atypical clinical manifestations than adults. Furthermore, they are at greater risk of progressing from infection to active disease, particularly if they are very young. Consequently, pediatricians have to use different diagnostic strategies that specifically address the needs of children. This document describes the recommendations of a group of scientific societies concerning the signs and symptoms suggesting pediatric TB, and the diagnostic approach towards children with suspected disease.

Estimation of mean number of daily hand hygiene procedures per patient can represent an effective and easy understandable method to evaluate adherence experience in a tertiary care pediatric hospital of Northern Italy.

INTRODUCTION: Hand decontamination with alcohol-based antiseptic agents is considered the best practise to reduce healthcare associated infections. We present a new method to monitor hand hygiene, introduced in a tertiary care pediatric hospital in Northern Italy, which estimates the mean number of daily hand decontamination procedures performed per patient. METHODS: The total amount of isopropyl alcohol and chlorhexidine solution supplied in a trimester to each hospital ward was put in relation with the number of hospitalization days, and expressed as litres/1000 hospitalization-days (World Health Organization standard method). Moreover, the ratio between the total volume of hand hygiene products supplied and the effective amount of hand disinfection product needed for a correct procedure was calculated. Then, this number was divided by 90 (days in a quarter) and then by the mean number of bed active in each day in a Unit, resulting in the mean estimated number of hand hygiene procedures per patient per day (new method). RESULTS: The two methods had similar performance for estimating the adherence to correct hand disinfection procedures. The new method identified wards and/or periods with high or low adherence to the procedure and indicated where to perform interventions and their effectiveness. The new method could result easy-to understand also for non-infection control experts. CONCLUSIONS: This method can help non-infection control experts to understand adherence to correct hand-hygiene procedures and improve quality standards.

SARS-CoV-2 and Burkholderia cenocepacia infection in a patient with Cystic Fibrosis: An unfavourable conjunction?

The effects of the concomitant infection by COVID-19 and Burkholderia cepacia (Bc) in CF are not known. We describe the case of a 34 years woman with CF, colonized by Bc and found SARS-CoV2 positive. In the first hospital week she suffered acute respiratory failure and chest imaging showed interstitial involvement and multiple thickenings. She was treated with antibiotics, dexamethasone, remdesivir and heparin, with gradual improvement and discharge at day 20th. The reciprocal role of SARS-CoV-2 and Bc, their potential interactions and the contribution of the individual therapies to the favourable outcome are unclear. It is debatable whether it was SARS-CoV2 that triggered a Bc pulmonary exacerbation or if the chronic Bc infection facilitated the development of a COVID-19 more aggressive than usually seen in CF. If the latter hypothesis were confirmed by similar cases, Bc colonization should be regarded as a risk factor for severe COVID-19 expression in CF.

Shifting from open surgical cut down to ultrasound-guided percutaneous central venous catheterization in children: learning curve and related complications.

PURPOSE: Tunneled indwelling central venous catheters (CVC) are essential in the management of children with cancer, hematological, nephrological disorders and for parenteral nutrition. The aim of this study is to present the experience of a single center of the transition from traditional open surgical cut down procedure (OSC) to ultrasound (US)-guided percutaneous CVC insertion, focusing on learning curve and related complications. METHODS: All CVCs inserted between April 2008 and November 2009 in children at the Gaslini Children Hospital were revised, and data on methods of cannulation, intraoperative and device-related complications and re-intervention were recorded. RESULTS: 194 CVCs were positioned in 188 patients. 128 out of 194 CVCs were positioned through an OSC technique, whereas the remaining 66 CVCs were inserted percutaneously with US guidance. Of the 27 recorded complications, 15 were mechanical events, 7 cases developed infection, whereas the remaining 5 (2.6%) were classified as intraoperative complications. A second surgical procedure was described in 23 (11.8%) cases. CONCLUSION: Shifting from OSC to US-guided percutaneous CVC insertion inevitably involves a challenging learning curve which is generally associated with high complication rates. Complications progressively decrease once a good experience in US guidance and percutaneous technique has been obtained.

Bacterial invasive infections in a neonatal intensive care unit: a 13 years microbiological report from an Italian tertiary care centre.

INTRODUCTION: To evaluate the aetiology of neonatal invasive diseases (positive cultures from blood or cerebrospinal fluid, CSF) due to bacteria other than coagulase-negative staphylococci in a large tertiary care centre and compare with results of surveillance cultures. METHODS: Retrospective analysis of microbiological data of children admitted in neonatal intensive care unit (NICU) of a large tertiary care centre from 2005 to 2018. RESULTS: 230 bacterial strains, 223 from blood and 7 from CSF, respectively, were detected as cause of invasive infections, while 152 were detected in surveillance cultures. Methicillin-susceptible Staphylococcus aureus (MSSA) was the most frequently isolated pathogen both in invasive infections (18%) and colonizations (23%) followed by Escherichia coli (16% on invasive disease and 20% of colonizations). Other common bacteria include Enterococcus faecalis and Streptococcus agalactiae for invasive disease and methicillin-resistant Staphylococcus aureus in colonizations. Invasive infection was due to a pathogen detected in surveillance cultures in 33% of cases. In more than 50% of invasive diseases the identified pathogen was not present in surveillance cultures. CONCLUSIONS: The high percentage of invasive infections due to bacteria not previously identified in surveillance cultures raises doubts about the efficiency of this procedure and highlights the need to search for alternative infection sources. This finding and the high prevalence of invasive infections due to nosocomial pathogens such as Staphylococcus aureus could be the result of horizontal transmission between patients through the hands of health care professionals, emphasizing once again the importance of applying stringent hand hygiene procedures and isolation standards.

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

Incidence of indwelling central venous catheter-related complications using the Sri Paran technique for device fixation in children with cancer.

PURPOSE: Mechanical complications in tunneled indwelling central venous catheters (CVCs) often involve a risk of displacement. Fixation procedures are, therefore, of primary importance. We prospectively evaluated the incidence of CVC-related mechanical and infectious complications observed in devices fixated with the Sri Paran technique. METHODS: All CVCs inserted in children with cancer at our Institution from October 2005 to January 2007 were prospectively monitored for device-related mechanical and infectious complications. The Sri Paran fixation technique was used in all cases. The complication rate per 1,000 days was calculated as 1,000 times the number of complications divided by the total number of catheter days. RESULTS: Ninety-five CVCs were positioned in 84 children. The overall length of observation ranged between 41 and 482 days for a total of 18,618 catheter days. Mechanical complications occurred in 5% of the devices (specific rate 0.27); infections were observed in 6% of the devices (specific rate 0.32). No complications were observed during the first 30 days after CVC insertion. CONCLUSIONS: The results, we obtained with the Sri Paran technique are extremely encouraging. Yet, randomized studies are required to prove these preliminary data.

Behaviours monitoring and infection control in neonatal intensive care unit: how to improve ourselves?

INTRODUCTION: Healthcare-associated infections are important events in neonatal intensive care unit.Hand hygiene is considered one of the most important procedures to control these complications. METHODS: Healthcare workers procedures for patient's approaching were directly monitored from February to April 2018 in the Neonatal Intensive Care Unit of Istituto Giannina Gaslini, Genoa, Italy.Number and type of total contacts with patients or "patient unit" (e.g.: ventilator, monitor, isolette) were recorded as well as errors related to lack of hand hygiene after and before performing procedures. RESULTS: A total of 1,040 actions were observed on patient or patient unit: 560 actions by nursing staff, 240 by residents and 240 by consultants. The most common misbehaviour was the "double touch" in nursing staff (30%), "glasses, hair or nose" in residents (35%), and "double touch" and "glasses hair or nose" in consultants (25% and 23% respectively). CONCLUSIONS: Extemporaneous contact is the more frequent potential "high risk" moment for transmission of healthcare associated infections in NICU.

ESCMID-ECMM guideline: diagnosis and management of invasive aspergillosis in neonates and children.

SCOPE: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children. METHODS: Review and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations. QUESTIONS: Questions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.

Bacteremias in children receiving hemopoietic SCT.

The incidence of bacteremia following hemopoietic SCT (HSCT) changes over time from the procedure. The first 30 days have the highest incidence, both in autologous and allogeneic HSCT recipients. In the following periods, bacteremia is a frequent complication in allogeneic HSCT, especially from alternative donors. Gram-positive cocci represent the most frequent cause of single-agent bacteremia. Knowledge of epidemiology (incidence and etiology) of bacteremias following HSCT is pivotal for planning management strategies (prevention, diagnosis and therapy) that must be distinct in the different post-transplant period.

Incidence of bacteremias and invasive mycoses in children undergoing allogeneic hematopoietic stem cell transplantation: a single center experience.

We performed a retrospective single center study to define the epidemiology of bacteremias or invasive mycoses in pediatric allogeneic hematopoietic SCT (HSCT) from matched related donors (MRD) or alternative donors (AD). During 119 213 days of follow-up, 156 infections were observed: 130 bacteremias (27 in MRD-HSCT and 103 in AD-HSCT recipients) and 26 invasive mycoses (8 in MRD-HSCT and 18 in AD-HSCT recipients). Overall, the risk of bacteremia was fivefold that of invasive mycosis (P<0.001). AD-HSCT recipients had a higher percentage of infections (89 vs 27%; P<0.001), a higher rate/100 days of immunosuppression (infection rate (IR): 0.21 vs 0.06; P<0.001) and a higher proportion of repeated infections (44 vs 9%; P=0.001). In AD-HSCT, the relative risk of bacteremia was 2.87 in the pre-engraftment period, 5.84 in the early post-engraftment period and 6.46 in the late post-engraftment period (P<0.001) compared to MRD-HSCT. Only after 1 year did the epidemiology become similar. The epidemiology of invasive mycoses did not differ significantly between the two types of transplant.

Rare viral infections in children receiving hemopoietic stem cell transplant.

Viral infections are a rare complication in autologous hemopoietic stem cell transplant (HSCT) recipients but represent a frequent cause of disease after allogeneic HSCT. In the last years, there has been an increase in the number of viral diseases observed in these patients. This fact may be at least partially due to an improvement in diagnostic facilities, but the increasing number of transplant procedures and the more severe immunosuppression may also have played an important role.

Invasive mycoses in children receiving hemopoietic SCT.

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.

Anti-varicella-zoster vaccination in contacts of children receiving antineoplastic chemotherapy: a prospective pilot study.

Varicella may be a severe infection in children with malignancy. Varicella vaccination is either not recommended for immunocompromised children or it requires temporary discontinuation of immunosuppression. We prospectively evaluated the feasibility of a varicella vaccination programme of household contacts of varicella-negative children receiving antineoplastic chemotherapy. From April 2004 to April 2005, 207 children were evaluated; in 49 (24 percent) the attending physicians collected no history about previous varicella and performed no serological evaluation before any transfusion. Among the 158 patients with complete history and/or a screening test, 51 (32 percent) were negative, with a total of 110 household contacts eligible for the study. Of these, 13 (12 percent) subjects resulted negative for varicella. In three of them vaccination was not performed due to parental refusal. This study demonstrates the difficulties in implementing a varicella vaccination programme targeting negative household contacts of immunocompromised children. The attitude of paediatric oncologists and parental refusal currently represent the main challenges against the complete success of this strategy in countries where VZV vaccination is not inserted in the general vaccination programme.

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Nebulized liposomal amphotericin B and combined systemic antifungal therapy for the treatment of severe pulmonary aspergillosis after allogeneic hematopoietic stem cell transplant for a fatal mitochondrial disorder.

Nebulized liposomal amphotericin B (20-15 mg twice daily by nebulizer) was combined with high dose intravenous liposomal amphotericin B (10 mg/kg/day) and high dose caspofungin (100 mg/m(2)) for the treatment of severe, recurrent pulmonary aspergillosis following allogeneic hematopoietic stem cell transplantation from alternative donor in a patient with mitochondrial disease (Pearson's syndrome). This combined treatment was administered for 8 days. Nebulized liposomal amphotericin B was well tolerated. Since severe transplant complications developed, nebulized administration was withdrawn and intravenous doses of liposomal amphotericin B and caspofungin were tapered to usual schedules. Pulmonary aspergillosis responded well to 45 days of combined intravenous antifungal therapies which were maintained for 2 years with secondary prophylaxis, because of persistent immunosuppressive treatment.

Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases.

From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR.

Differences in the proportions of fluoroquinolone-resistant Gram-negative bacteria isolated from bacteraemic children with cancer in two Italian centres.

The proportion of ciprofloxacin-resistant Gram-negative bacteria isolated from the blood of children with cancer (not receiving prophylaxis) was 10% in a paediatric hospital (Genoa) where the use of quinolones was highly restricted, compared with 41% in a department of haematology (Rome) where leukaemic adults, who received fluoroquinolone prophylaxis, were also treated (p < 0.0001). Moreover, simultaneous resistance to ciprofloxacin and ceftazidime, amikacin or imipenem-cilastatin was 11% in Genoa compared with 37% in Rome (p < 0.001). Ciprofloxacin resistance was more frequent in children who shared an environment with adults who were receiving ciprofloxacin prophylaxis.

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.