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Objectives: We summarized the clinical and radiological characteristics of meningitis-retention syndrome (MRS), its therapeutic options, and urological outcome, to better understand the pathogenesis of this syndrome and to evaluate the effectiveness of corticosteroids in reducing the period of urinary retention., Methods: We reported a new case of MRS in a male adolescent. We also reviewed the previously 28 reported cases of MRS, collected from inception up to September 2022., Results: MRS is characterized by aseptic meningitis and urinary retention. The mean length of the interval between the onset of the neurological signs and the urinary retention was 6.4 days. In most cases, no pathogens were isolated in cerebrospinal fluid, except for 6 cases in which Herpesviruses were detected. The urodynamic study resulted in a detrusor underactivity, with a mean period for urination recovery of 4.5 weeks, regardless of therapies., Discussion: Neurophysiological studies and electromyographic examination are not pathological, distinguishing MRS from polyneuropathies. Although there are no encephalitic symptoms or signs, and the magnetic resonance is often normal, MRS may represent a mild form of acute disseminated encephalomyelitis, without radiological detectable medullary involvement, due to the prompt use of steroids. It is believed that MRS is a self-limited disease, and no evidence suggests the effectiveness of steroids, antibiotics, and antiviral treatment in its clinical course., (© 2023. The Author(s).)

Malaria is not endemic in Italy, however every year about 600-700 imported cases are detected in people born or living in Italy who return from a stay in their country of origin (visiting friends and relatives - VFR). Children account for 20% of this population and they have an higher risk of severe disease. Socio-economic problems and deficiencies in the doctor-patient relationship often lead to a lack of awareness of the importance of prophylaxis, making the category of VFRs at increased risk of disease. The aim of this study is to analyze the characteristics of pediatric imported malaria, with a specific focus on prevention and risk factors for severe malaria. All malaria cases diagnosed from 2007 to 2019 in Ospedale Infantile Regina Margherita in Turin were retrospectively observed. Epidemiological and clinical data were described. A total of 72 patients were reported: 98.6% had African origins and 73.6% traveled as VFRs. Plasmodium falciparum was the species most commonly isolated (94.4%). Twenty-four patients (33.3%) underwent chemoprophylaxis and never appropriately. Patients not undergoing prophylaxis and those undergoing incomplete prophylaxis showed not statistically significant difference in term of disease severity (p = 0.26). Nineteen cases were considered severe, including 3 with cerebral malaria. High levels of parasitemia were statistically significantly correlated with severe anemia (p = 0.049) and severe thrombocytopenia (p = 0.036). In 25% of cases the first diagnosis was incorrect. The therapeutic use of artemisinin derivatives has resulted in a significant shortening of the parasitemia clearance time compared to the use of other drugs (p < 0.001). Families have to be educated about the serious implications of a malaria infection and the importance of a correct and complete prophylaxis. Clinicians should always consider malaria in the differential diagnoses in patients with fever and a history of a recent travel to an endemic area. Prompt diagnosis and use of appropriate drugs, according to the latest guidelines, could guarantee a better outcome for patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategies as antimicrobial stewardship programs, aiming to preserve our antibiotic armamentarium, have been implemented since 2007 in adult and paediatric patients. We aim to describe the first experience of a paediatric antimicrobial stewardship program. We conducted a retrospective observational study in a tertiary care children's hospital. A team composed of a microbiologist, an infectious diseases physician, and a paediatrician led the project. All positive blood and cerebrospinal fluid cultures and other biological samples yielding multi-drug-resistant bacteria were collected and reviewed through a prospective-audit-with-feedback strategy. We recorded patient characteristics and worth monitoring prescribed antibiotics. The antimicrobial stewardship audit could end in intervention (step-up/step-down and broadening/narrowing) or recommendation(s). We then checked out wards staff compliance. The team performed 192 interventions out of 584 reviews, mostly suggesting discontinuation of antibiotics (in 76.0% of cases and 39.7% of running molecules). The antibiotic spectrum was more likely tapered than expanded (p < 0.0001), and we ordered more narrow-spectrum antibiotic molecules than local medical staff straightaway did (p = 0.0113). Interventions were most likely needed in case of documented infections (p < 0.0001) and in surgical patients (p = 0.0002). In 85.9% of interventions, ward teams fully agreed with our argument. This study demonstrated an antimicrobial stewardship program to be a suitable method for improving the appropriateness of antimicrobial use in hospitalized children., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

Background: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant., Objectives: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children., Methods: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases., Results: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred., Conclusions: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach., (© 2020 International Society on Thrombosis and Haemostasis.)

Little is known about the sequelae of SARS-CoV-2 infection in children. In a COVID-19 dedicated clinic, we followed-up for 4 months 25 children previously hospitalized for COVID-19, performing clinical, laboratory, and lung ultrasound evaluation. Mid-term sequelae were rarely observed in our COVID-19 children's cohort.

Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiological syndrome that can be related to infectious and non-infectious conditions. The most prominent neurological symptoms are disturbance of consciousness, abnormal speech, delirious behavior, seizures, muscle weakness, ophthalmoplegia, facial nerve paralysis and headache. Here we report the case of a child with MERS presenting with the unusual symptom of bilateral transient blindness., Case Presentation: A 4-year-old female patient, with a history of fever, abdominal pain, loss of appetite and cough lasted for a few days, experienced 3 episodes of transient bilateral loss of vision with difficulty in walking. Her physical examination showed absence of focal neurological and meningeal irritation signs, although responsiveness was slightly impaired. The ophthalmologic evaluation, including a fundus oculi examination, was negative. The electroencephalogram showed slow activity in the temporo-occipital regions, more evident in the right hemisphere. A lumbar puncture was performed and cerebrospinal fluid analysis revealed normal glycorrhachia, cell counts, protein levels and IgG index. Magnetic resonance imaging of the brain showed a signal alteration in the splenium of the corpus callosum, without contrast enhancement. This finding was suggestive of a reversible cytotoxic lesion. Empiric antiviral treatment with acyclovir and intravenous dexamethasone was initiated. Polymerase chain reaction search for neurotropic viral nucleic acid sequences in the cerebrospinal fluid was negative, while a low number of HHV-6 DNA copies was detected in the blood. Electroencephalograms were repeated in the following days, showing a progressive normalization of the pattern. The child was discharged without symptoms after 10 days of treatment with oral corticosteroids. After 40 days, brain magnetic resonance imaging showed a complete normalization of the signal alteration in the splenium of the corpus callosum., Conclusion: Transient blindness was reported as an initial symptom of MERS in a few children. To date, there is no evidence of effective treatment methods. Nonetheless, MERS diagnosis provides pediatricians with valuable prognostic information in order to reassure patients and their families about the good outcome of this disease.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa , it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis., (Copyright © 2020 Garazzino, Altieri, Silvestro, Pruccoli, Scolfaro and Bignamini.)

Although few cases of bacteremia or sepsis caused by probiotics have been reported, it is important to consider their pathogenic potential, especially in some categories of patients. We report a case of Bifidobacterium spp bacteremia in a child with heart disease, undergoing probiotic supplementation to prevent antibiotic-associated diarrhea.

Pediatric neck masses are a common occurrence and often represent a diagnostic challenge. The primary aim of this retrospective study was to evaluate the clinical and radiological features of neck masses in children and how they can drive diagnosis. The secondary aim was to create a diagnostic algorithm based on clinical features. We evaluated 190 children with neck masses who needed hospitalization. Clinical data and imaging findings were collected. The patients were divided into six groups: congenital/developmental lesions, tumors, acute and subacute lymphadenopathies, chronic nonspecific lymphadenopathies, cat-scratch disease, and mycobacteriosis. Reactive lymphadenopathies were observed in the majority of cases (65.8%). Congenital/developmental cysts were present in 28.9%, while 5.3% had a tumor. A lower mean age was observed for acute/subacute lymphadenopathies and mycobacteriosis. Fever and a painful mass were typical of acute/subacute lymphadenopaties and cat-scratch disease. A hard and fixed mass was not only typical of tumors. Concerning imaging findings, multiple lymph nodes at the same level was mainly observed in mycobacteriosis, while bilateral lymph node enlargement and colliquation were present in lymphadenopathies.Conclusion:A complete and adequate clinical assessment should be the basis for every diagnostic and therapeutic choice in children with neck masses. What is Known: • Pediatric neck masses are a common occurrence and often represent a diagnostic challenge. • Clinical features, serological exams and imaging findings should drive the physician to an appropriate diagnostic hypothesis. What is New: • A lower mean age was observed for acute/subacute lymphadenopathies and mycobacteriosis. • A hard and fixed mass was not only typical of tumors. • Multiple lymph nodes at the same level were mainly observed in mycobacteriosis, while bilateral lymph node enlargement and colliquation were present in nonspecific lymphadenopathies.

Background: Malnutrition constitutes one of the major public health challenges throughout the developing world. Urban poverty and malnutrition have been on the rise, with an increased rate of morbidity. We herein explore the relationship between infections and nutritional status and the related association with hygienic conditions as risk of infection in children residing in the slums of Nairobi., Methods: Case-control study based on a secondary analysis of quantitative data collected from a cluster randomized trial carried out in two slums of Nairobi. The following information about resident children were selected: babies' anthropometric measurements, related life conditions, data on infant-feeding practices, food security, hygiene, immunization coverage and morbidity were collected and updated with structured questionnaires until 12 months of life. Prevalence of malnutrition was calculated, then both bivariate and multivariate analysis were used to explore the relationship between malnutrition and its determinants., Results: The study involved a total of 1119 babies registered at birth (51.28% male and 48.03% female infants). Overall the prevalence of malnutrition was high, with 26.3% of the children being stunted, 6.3% wasted and 13.16% underweight. Prevalence of wasting was higher in the first months of life, while in older children more case of stunting and underweight were captured. Wasted infants were significantly associated with common childhood illnesses: with cough and rapid breathing as well as with diarrhea (p-value< 0.05). Stunting was associated with hygienic conditions (p-value< 0.05 in households that did not perform any water treatment and for children that had a toilet within the house compound), immunization program and low-birth-weight. Moreover, regression analysis showed that significant determinants of stunting were sex and feeding practices. Underweight was significantly associated with socio-demographic factors., Conclusions: In the specific environment where the study was conducted acute malnutrition is correlated with acute infections, while chronic malnutrition is more influenced by WASH conditions. Therefore, our findings suggest that one cannot separate infection and its risk factors as determinants of the whole malnutrition burden.

A prospective 18-month case-control study was performed in a tertiary Paediatric Centre in Turin (Italy) to analyse the disease burden and identify risk factors for acquisition of Extended Spectrum Beta Lactamase-producing Enterobacteriaceae (ESBL-pE). Children with ESBL-pE isolation were enrolled as cases, with controls matched according to age, type of pathogen isolated and sample of isolation. Out of 83 children (37 males, mean age 4.7 ± 5.46 years), 45 were identified as infected (54.2%) and 38 as colonised (45.8%) by ESBL-pE. Twenty-nine (64.4%) infectious disease episodes were categorised as community-acquired, 16 (35.6%) as healthcare-associated. Escherichia coli was the most frequently isolated pathogen (52, 62.7%) and the urinary tract the most frequent site involved (26, 57.9%). No deaths occurred, even in bloodstream infection cases. Hospitalisation and exposure to broad-spectrum penicillins and III/IV generation cephalosporins in the 90-day period before bacteria isolation were found to be independent risk factors at multivariate analysis. Immunodepression, prolonged central venous catheter (CVC) and urine catheter stay, and receiving a total parenteral nutrition (TPN) in the previous 30 days were otherwise recognized as potential risk factors at univariated analysis. ESBL-producing Enterobacteriaceae infections are a growing threat even in children. Careful recognition of patients at risk should promote targeted interventions in order to reduce the ESBL burden.

Unlabelled: Sepsis is the major cause of morbidity and mortality in children, especially in immunocompromised patients, and a rapid identification of causative pathogen is strongly related with a better outcome. This prospective study analyzes the role of a multiplex real-time polymerase chain reaction in sepsis' etiological diagnosis. Magicplex(TM) Sepsis Real-Time tests were performed in tertiary Regina Margherita Children's Hospital (Turin, Italy), and the medical records of children who underwent a Magicplex test were prospectively evaluated. Results of the Magicplex test were compared with those of blood culture collected at a close time point. One hundred fifty Magicplex tests were collected from 89 patients (54 males and 35 females, age interquartile range: 2.6-12.1 years). Etiological definition was achieved in 60 bloodstream infection cases (40 %). In 32 episodes, Magicplex test alone gave a positive result, and blood culture alone permitted the etiological diagnosis in 5 septic episodes. Magicplex test allowed a 143 % increase in the diagnostic value of blood cultures., Conclusion: These results suggest that molecular biology can be useful for rapid pathogen's identification also in children., What Is Known: • Sepsis represents a major cause of morbidity and mortality in children. • Sepsis outcome is strongly related to rapid microbiological identification and prompt initiation of an appropriate chemotherapy. What is New: • This manuscript is the first that describes the use of Magicplex (TM) Sepsis Real-Time test in children. • The results suggest that molecular biology can be useful for rapid pathogen's identification also in children.

Background: The spread of carbapenem-resistant Enterobacteriaceae (CRE) is a health problem of major concern. CRE-related infections have significant morbidity and mortality, but data on CRE infection in pediatric population are limited. The aim of this study was to analyze epidemiologic and clinical characteristics, risk factors, therapeutic options and outcome of CRE infections in children in Italy., Methods: We performed a retrospective, multicenter, observational study of children with confirmed CRE infection or colonization admitted between January 1, 2011, and March 1, 2014, to 7 Italian pediatric centers., Results: Sixty-nine patients presenting 74 CRE infections and/or colonization were included. The most frequently isolated strain was Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Children with CRE infections had longer length of stay in hospital (P < 0.001), duration of disease (P = 0.001) and antimicrobial treatment (P < 0.001) than colonized children. Oncologic/immunosuppressive conditions are one of the factors significantly associated with a fatal outcome among children with CRE infections., Conclusions: Our study confirms that CRE infections affect mostly children with oncologic diseases and immunosuppression. Controlled studies in large cohorts are needed to evaluate the best therapeutic options and to assess further risk factors influencing outcomes and the survival of pediatric patients with infections caused by CRE.

The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

The aim of this survey was to describe the incidence, epidemiology, microbiology, risk factors and outcome of medical care related laboratory-confirmed bloodstream infections (LCBIs) observed during a twelve-month prospective study in a Paediatric Teaching Hospital in Turin, Italy. Inclusion criteria were clinical signs of sepsis and positivity of one or more of the following tests: blood culture, polymerase chain reaction for bacterial and fungal DNA on blood, and culture on intravascular device tips. In all, 140 episodes of sepsis were documented in 131 children: 37 (26.4%) were healthcare outpatient-associated, 91 (65.0%) healthcare-associated and 12 (8.6%) community-acquired. The overall incidence of healthcare-associated LCBIs was 13.6/1,000 hospitalized patients and incidence density 1.4/1,000 inpatient days. The overall mortality was 3.9%. Forty-seven (36.7%) episodes involved newborns and 107 (83.6%) episodes were observed in children with an indwelling central venous catheter. Coagulase-negative staphylococci (26.8%), Staphylococcus aureus (15.2%), Escherichia coli (8.7%) and Candida spp. (7.2%) were responsible for the majority of cases. 9.5% of S. aureus isolates were methicillin-resistant and 6.5% of Gram negatives were extended-spectrum beta-lactamase-producing. Incidence and epidemiology of medical care related LCBIs were similar to the existing literature data. LCBIs caused by antibiotic-resistant microorganisms were fewer and mortality rate was lower. Most of the LCBIs recorded involved newborns and oncological children.

Background: The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, making the application of molecular methods quite promising., Methods: Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics--LC-SF) performed in the tertiary centre of Regina Margherita Children's Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point., Results: 545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7-13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohen's kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected., Conclusions: BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.

Deep neck infection (DNI) is a severe occurrence in children. We've examined the presenting signs and symptoms, the value of single diagnostic procedures, the rate of complications and the impact of the therapeutic options on the final outcome, in children with a DNI. We retrospectively evaluated patients, aged 0-18 years, who were admitted for a DNI, from January 2006 through December 2012, at Regina Margherita Children's Hospital, Turin, Italy. We subdivided them on the basis of type of treatment: pharmacological treatment alone or antimicrobial treatment plus surgery. An univariate analysis has been performed to examine the differences between the two groups. Sixty patients (32 males, 28 females) with diagnosis of DNI were enrolled; 33 children only received medical treatment (group 1), whereas 27 patients underwent also surgical interventions (group 2). The mean abscess size was significantly higher in group 2 than in group 1 (p = 0.01). The predominant organisms were Streptococcus sp. (11 cases, 52.4%, mostly Streptococcus pyogenes). The most frequent antibiotic regimen was a β lactam alone (either III generation cephalosporin or amoxicillin/clavulanate). The duration of intravenous antibiotic varied between the two groups, without statistical significance (p = 0.052); whereas the oral antibiotic administration was significantly shorter in group 1 than in group 2 (p = 0.0003). Three patients (5%) developed complications. This research confirms that the medical approach, with high doses of intravenous antibiotics for a minimum of 5 days, could be a tolerable and safe option for the treatment of patients with stable condition and/or small DNIs., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Drug-resistant paediatric tuberculosis (TB) is an overlooked global problem. In Italy, the epidemiology of TB has recently changed and data regarding drug-resistant forms in the paediatric setting is scanty. The aim of this case series was to report the cases of drug-resistant TB, diagnosed between June 2006 and July 2010 in four Italian tertiary centres for paediatric infectious diseases, in children and adolescents living in Italy. Twenty-two children were enrolled, of these 17 were resistant to one or more drugs and five had multidrug-resistant TB. All but one child were either foreign born or had at least one foreign parent. Twenty-one patients completed their treatment without clinical or radiological signs of activity at the end of treatment, and one patient was lost to follow up. The outcomes were good, with few adverse effects using second-line anti-TB drugs. Although this series is limited, it might already reflect the worrisome increase of drug-resistant TB, even in childhood.

Unlabelled: The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria., Conclusions: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.

Non-tuberculous mycobacteria are one of the major causes of lymphadenitis in children and seldom of deep neck infections. We reported the case of an immunocompetent two-year-old girl with adenitis and retropharyngeal abscess caused by an atypical mycobacterium. She had a positive tuberculin skin test, whereas the Quantiferon TB Gold test was negative. The child underwent a complete nodal excision. The search for acid fast bacilli was positive and Mycobacterium scrofulaceum was isolated from the surgically removed material. The retropharyngeal abscess was treated only with antimicrobial therapy, which resulted in an appreciable size reduction of the abscess. After two months antimicrobial treatment was interrupted, and complete resolution was achieved after twelve months. No relapse of disease or possible long-term complications were observed. The surgical wound healed completely, with normal overlying skin and a good aesthetic result. The clinical management of atypical mycobacteria lymphadenitis and retropharyngeal abscess in children is discussed.

Objective: To report our experience on the safety and tolerability of moxifloxacin for treating children affected by pulmonary TB., Study Design: Children receiving a moxifloxacin-containing anti-TB regimen were included in the study. Their medical records were revised at the end of follow-up., Methods: We describe nine children treated with moxifloxacin for pulmonary TB at Regina Margherita Children's Hospital (Turin, Italy) between 2007 and 2012. Moxifloxacin was administered orally at 10 mg/kg/day once daily (maximum dose = 400 mg/day) following World Health Organization indications. During treatment, patients were systematically assessed for the development of side effects., Results: Eight children were considered cured at the end of treatment; one child was lost to follow-up after 3 months of treatment. Two children had side effects during treatment: one developed arthritis of the ankle; the other had liver toxicity, whose relationship with moxifloxacin could not be ruled out. We did not observe any case of QT prolongation, central nervous system disorders, growth defects or gastrointestinal disturbances., Conclusions: A moxifloxacin-containing regimen might be considered for the treatment of TB in children, especially for drug-resistant and extensive forms. However, vigilance for possible side effects is recommended, especially if other drugs are concomitantly used. Studies on wider populations are needed to better define the impact of long-term treatments with quinolones on children's growth and psychomotor development and to outline regulatory indications on moxifloxacin use in the pediatric setting., (© 2013 Wiley Periodicals, Inc.)

Tuberculosis keeps on representing a serious threat worldwide and one of the major challenge of our century. Different strategies have been developed in order to eradicate the disease, and particular attention is paid to children, who are at great risk for developing severe manifestations and poor outcome. Age at exposure, nutritional conditions and immune status can lead to great variability of disease expressions, with subsequent difficulties in making an appropriate and rapid diagnosis. Moreover, children coming from tuberculosis-endemic areas should be carefully evaluated for M. tuberculosis infection. Here we present a infrequent manifestation of extrapulmonary tuberculosis in a 13-years-old girl coming from Latin America: a superficial persistent cervical lymphadenopathy was associated with a totally asymptomatic retropharyngeal abscess. Diagnostic approach was discussed. Treatment consisted with a combination of surgical drainage of the abscess and a prolonged combined 6-month chemotherapy. The cervical lymphadenopathy disappeared and no relapses were found during the subsequent follow up.

We describe a case of acute disseminated encephalomyelitis (ADEM) occurring in a three-year old girl with influenza A (H1N1)v infection and manifesting with seizures and ataxia. The brain MRI revealed bilateral hyperintense signal changes in basal ganglia and brain stem. The patient was treated with intravenous methylprednisolone bolus followed by tapering steroids and progressively recovered without neurologic sequelae at the latest follow-up. ADEM may represent a rare postinfectious complication following novel pandemic influenza A H1N1v which should be taken into account in the differential diagnosis of associated neurologic manifestations for the specific therapeutic approach and adequate follow-up.

Oral myiasis is a condition in which tissues of the oral cavity are invaded by the larvae of flies. It is a rare disease in humans, often associated with very poor dental and oral hygiene. In children the main predisposing factors are incompetent lips, thumb sucking habits and continuous mouth breathing. The condition has been reported mainly in Asia and South America and rarely in more developed countries. The cases recorded in Italy concern adults with ocular or cutaneous manifestations alone. We describe an unusual infestation of the oral cavity of a five-year-old Italian boy with a severe congenital heart defect. He presented a gingival swelling and, after a few hours, some larvae could be seen moving through his oral cavity. They were removed manually and an oral antibiotic was given to avoid a bacterial superinfection. Three days after, oral examination of the patient revealed a gradual decrease in gingival swelling; complete clinical resolution was achieved about two weeks later. This case is reported as a reminder to consider oral myiasis in the event of suspected gingival swelling in children, especially if they have predisposing factors or if they come from an endemic area.

Introduction. Invasive bacterial diseases continue to represent a significant burden in paediatric age, and the emergence of previously secondary bacteria and antibiotic-resistant strains requires a continuous surveillance. Materials and methods. A one-year prospective survey on laboratory confirmed community-acquired bloodstream infections (CA-LBSIs) cases admitted to an Italian tertiary specialistic paediatric Hospital. Results. Twelve cases were documented, with an incidence rate of 0.39/1,000 admissions to the Emergency Department, and of 2.9/1,000 hospitalizations to general and specialized wards. Mean age at diagnosis was 5.2 +/- 5.9 years, with 58.3% of episodes regarding children younger than years. Six episodes were caused by Gram positive and six by Gram negative bacteria, with potential vaccine-preventable pathogens responsible of 50% of CA-LBSIs. Empiric antibiotic therapy prescribed at admission was found appropriate to microbiological results in the totality of cases and administered for a mean time of 17.7 +/- 10.1 days. No resistant strains were found. All patients had a good outcome. Conclusions. Prompt collection of samples for microbiological tests together with the rapid institution of empiric antibiotic therapy are essential for the correct management of CA-LBSIs in paediatric patients. Implementation of vaccinations against the major responsible pathogens remains the most important prevention strategy.

Objectives: Because of the spread of drug-resistant Gram-positive bacteria, the use of linezolid for treating severe infections is increasing. However, clinical experience in the paediatric population is still limited. We undertook a multicentre study to analyse the use of linezolid in children., Methods: Hospitalized children treated with linezolid for a suspected or proven Gram-positive or mycobacterial infection were analysed retrospectively. Side effects were investigated, focusing on younger children and long-term treatments., Results: Seventy-five patients (mean age 6.8 years, range 7 days to 17 years) were studied. Mean ± SD linezolid treatment duration was 26.13 ± 17 days. Clinical cure was achieved in 74.7% of patients. The most frequent adverse events were diarrhoea and vomiting. Two patients had severe anaemia, two neutropenia and one thrombocytopenia. Two cases of grade 3 liver function test elevation and one case of pancreatitis were reported. The overall frequency of adverse events was similar between patients treated for >28 days and those receiving shorter treatments (30.8% versus 28.6%, P = 0.84). Children aged <2 years received linezolid for a shorter duration than older children (21.2 days versus 28.4 days, P = 0.05), whereas the frequency of adverse events was similar in the two age groups., Conclusions: In our paediatric population, linezolid appeared safe and effective for the treatment of selected Gram-positive and mycobacterial infections. The adverse reactions encountered were reversible and appeared comparable to those reported in paediatric clinical trials. Nevertheless, the potential for haematological toxicity of linezolid in children means that careful monitoring is required during treatment.

Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant systems, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation should comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

Neurocysticercosis represents an important cause of seizures in children in endemic countries, such as Latin America, Asia and sub-Saharan Africa, while in Europe, especially in Italy, the cases of neurocysticercosis are anectodal. We report the case of a 6 year old boy, born and lived for four years in Cameroon, who presented a right emiconvulsion. The diagnosis was neurocysticercosis. This case accentuates the need to consider neurocysticercosis in a child presenting with non febrile seizures, mainly if he emigrated from an area of high prevalence or if he had long-term stay in endemic regions.

Background: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit., Methods: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0-18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs., Results: The study included 260 patients, with a mean age of 4.3 ± 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs., Conclusion: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management., (Copyright © 2012 S. Karger AG, Basel.)

Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants.

We report here 2 pediatric cases of multidrug-resistant (MDR) tuberculosis (TB) that were observed in Italy. Both families came from an Eastern European country, which is notably an area with a high prevalence of MDR TB. An increase of new cases of MDR TB in developed countries is expected over the next years because of migratory flow, and specific measures and strategies need to be taken to prevent the propagation and dissemination of MDR TB. An efficacious treatment including linezolid and moxifloxacin was administered for 13 months in 1 case. No adverse reactions were detected during close child monitoring. Linezolid and newer fluoroquinolones such as moxifloxacin have been reported to be effective for MDR-TB treatment in adults. On the contrary, there is limited available evidence regarding the effectiveness and safety of these drugs in infants and children with MDR TB. The use of second-line drugs not approved for use in children may be necessary to treat a life-threatening disease such as MDR TB, but it requires careful monitoring to quickly recognize the occurrence of dose- and duration-dependent adverse drug reactions.

This prospective observational study was designed to assess the incidence of, risk factors for, and outcome of catheter-related bloodstream infection in children undergoing cardiac surgery. A staff specifically trained to handle the central venous catheters with proper aseptic techniques and an appropriate patient to medical staff ratio remain the most effective measures to prevent this infection.