Diagnosis and management of deep neck infections in children: the experience of an Italian paediatric centre.

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 ß 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.

Natural history of vertically acquired HCV infection and associated autoimmune phenomena.

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.

Use of linezolid in infants and children: a retrospective multicentre study of the Italian Society for Paediatric Infectious Diseases.

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 ±â€ŠSD linezolid treatment duration was 26.13 ±â€Š17 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.

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged <90 days with LOS. METHODS AND FINDINGS: NeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of ≤44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA >44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.

Mannose-Binding Lectin: Biologic Characteristics and Role in the Susceptibility to Infections and Ischemia-Reperfusion Related Injury in Critically Ill Neonates.

The mannose-binding lectin (MBL) is a member of the collectin family, belonging to the innate immunity system. Genetic, biologic, and clinical properties of MBL have been widely investigated throughout the last decades, although some interesting aspects of its potential clinical relevance are still poorly understood. Low circulating concentrations of MBL have been associated with increased risk of infection and poor neurologic outcome in neonates. On the other hand, an excessive and uncontrolled inflammatory response by the neonatal intestine after the exposure to luminal bacteria, leading to an increased production of MBL, may be involved in the onset of necrotizing enterocolitis. The purpose of the present review is to summarize the current knowledge about genetic and biologic characteristics of MBL and its role in the susceptibility to infections and to ischemia-reperfusion related tissue injuries to better explore its clinical relevance during the perinatal period and the possible future therapeutic applications.

Epidemiology and clinical outcomes of multidrug-resistant, gram-negative bloodstream infections in a European tertiary pediatric hospital during a 12-month period.

BACKGROUND: Bloodstream infections caused by multidrug-resistant, Gram-negative (MDRGN) bacteria represent a significant cause of morbidity and mortality. Prompt diagnosis and appropriate empiric treatment are the most important determinants of patient outcome. The objective of our study was to assess the epidemiology and clinical outcome of MDRGN sepsis in a tertiary-care pediatric hospital during a 12-month period. METHODS: It was a retrospective, observational study of MDRGN bacteremia including all patients <18 years of age, hospitalized during 2011, with documented bacteremia caused by Enterobacteriaceae or non-fermentative bacteria. RESULTS: Overall, 136 blood cultures in 119 patients were included. The median age of patients was 1.1 years; 86.3% of patients had an underlying disease. The cumulative incidence of Gram-negative bloodstream infections was 5.4/1000 hospital admissions and the infection rate was 0.65/1000 hospital days. Most frequently isolated strains were Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa; 67.6% of infections were hospital acquired. The percentage of multidrug-resistant (MDR) organisms among isolated species was 39%. The crude rate of mortality was 16% and sepsis-related mortality was 9.2%. The mortality rate among patients with an antibiotic-resistant isolate was 22.6%. Factors significantly associated with sepsis-related mortality were antibiotic resistance (odds ratio: 4.26, 95% confidence interval: 1.07-16.9) and hospital acquisition of infection (odds ratio: 1.13, 95% confidence interval: 1.05-1.22). CONCLUSIONS: This study demonstrates the high mortality of hospital-acquired MDRGN bacteremia in children. International networks focusing on clinical management and outcomes of MDRGN in children are required. Study of novel antibiotics active against Gram-negative bacteria should include children early in the clinical trial development programs.

New antibiotics for paediatric use: a review of a decade of regulatory trials submitted to the European Medicines Agency from 2000--why aren't we doing better?

New initiatives have been introduced in Europe and the USA to encourage more rapid development of antibiotics. The need to ensure these new antibiotics can be safely used in children, and especially neonates, is important owing to high antimicrobial resistance in these patient groups. This review aims to determine what lessons can be learnt from the recent regulatory processes to speed up access to new medicines for children, focusing on antibiotics licensed for adults by the EMA since 2000. For the 11 newly approved antibiotics, 31 clinical trials enrolling children in Europe were identified. However, many of these trials included both adults and children but did not provide a subset analysis for paediatrics, limiting the relevance of their findings. Some studies have been prematurely terminated and others are apparently active but are still not yet recruiting patients. Among paediatric-specific studies, 18 evaluate safety and efficacy of new compounds, 4 are pharmacokinetic studies, but only 2 focus on neonates. Nearly all studies with an agreed Paediatric Investigation Plan have just started or are not yet recruiting. For most antibiotics, despite adult phase 3 studies being completed, with specific concerns for particular drugs already noted, it will take another 3-5 years before adequate prescribing information becomes available for paediatricians. Evidence from this review suggests that we could do better. Lessons should be learnt from paediatric antiretroviral development, with neonatal and paediatric pharmacokinetic, clinical trial and pharmacovigilance drug development programmes being run directly in parallel with adult studies-not a decade behind.

Two pediatric cases of multidrug-resistant tuberculosis treated with linezolid and moxifloxacin.

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.