Pediatric urogenital schistosomiasis diagnosed in France.

BACKGROUND: Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children. METHODS: Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively. RESULTS: A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases. CONCLUSION: Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes.

Determinants of incomplete vaccination in children at age two in France: results from the nationwide ELFE birth cohort.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician). CONCLUSIONS: Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions. WHAT IS KNOWN: • Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions. WHAT IS NEW: • High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

Distribution, Consequences, and Determinants of Time to Antibiotics in Children With Community-Onset Severe Bacterial Infection: A Secondary Analysis of a Prospective Population-Based Study.

OBJECTIVES: To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs). DESIGN: Secondary analysis of the available data from a prospective population-based study from 2009 to 2014. SETTING: An administrative area in western France accounting for 13% of the national pediatric population. PATIENTS: All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine. CONCLUSIONS: For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs.

Suboptimal care was frequent in severe child physical abuse cases and was mainly related to delayed diagnoses and ineffective secondary prevention.

AIM: Our aim was to assess suboptimal care before a diagnosis of severe child physical abuse in western France. METHODS: A confidential inquiry was carried out, based on children under 6 years of age who were hospitalised in the Nantes regional university hospital from 2016 to 2018. Two researchers retrospectively reviewed the medical records of all the children who were reported to the authorities for suspected severe child physical abuse. Two experts determined the optimality of care and identified the main categories of suboptimal care. RESULTS: The median age of the 94 children included in the study was 8 months. A fifth of them had intra-cranial injuries and a quarter had fractures. One child died and a third had severe sequelae at hospital discharge. Included children frequently (37%) received suboptimal care before the diagnosis of severe CPA and this fell into two categories: delayed diagnosis was experienced by 17% and ineffective secondary prevention by 22%. CONCLUSION: Suboptimal care for severe child physical abuse was frequent and fell into two categories: delayed diagnosis and ineffective secondary prevention. These results can help us to design corrective actions.

A simple clinical decision rule may help to rule out severe bacterial infection and spare antibiotics in febrile young children.

AIM: To assess the performance of a new clinical decision rule (CDR) to identify patients at a low risk of invasive bacterial infection (IBI) among febrile children and its theoretical impact on antibiotic use. METHODS: Prospective study including consecutive children <5 years of age who presented in one French paediatric emergency department with fever without source between January and December 2016. With the collected data, we constructed a CDR based on a sequential approach based on age, clinical toxic signs, urinalysis and procalcitonin level. We evaluated its diagnostic performances to identify IBI and its potential impact on antibiotic use. RESULTS: Among the 1061 children (IBI 11/1061, 1.0%), 693 (65.3%) were classified at low or intermediate risk of IBI, with an IBI prevalence of 0%. The sensitivity and specificity of the CDR to predict IBI were 100% and 73.9%. Negative and positive predictive value were 100% and 3.9%, respectively. Using this new CDR, the current antibiotics exposure would theoretically be reduced from 33.6% to 24.1%. CONCLUSION: The promising interest of this clinical decision rule, using simple and accessible biological and clinical tools, needs to be confirm with an external validation study, which will allow its use in clinical practice.

[Illustrated case study of a patient with pediatric multisystem inflammatory syndrome]. / Cas clinique illustré autour d'un patient atteint d'un syndrome inflammatoire multisystémique pédiatrique.

Between November 2020 and June 2021, twelve children were treated at a university hospital in western France for pediatric multisystem inflammatory syndrome (PIMS). While the clinical presentation may have been reminiscent of Kawasaki disease, PIMS, a new nosological entity, was mentioned in the media in the context of the Covid-19 pandemic. In 2023, research into this syndrome will continue in France and Europe.

Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.

Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Impact of routine S100B protein assay on CT scan use in children with mild traumatic brain injury.

OBJECTIVES: To evaluate the impact of implementing a modified Pediatric Emergency Care Applied Research Network (PECARN) rule including the S100B protein assay for managing mild traumatic brain injury (mTBI) in children. METHODS: A before-and-after study was conducted in a paediatric emergency department of a French University Hospital from 2013 to 2015. We retrospectively included all consecutive children aged 4 months to 15 years who presented mTBI and were at intermediate risk for clinically important traumatic brain injury (ciTBI). We compared the proportions of CT scans performed and of in-hospital observations before (2013-2014) and after (2014-2015) implementation of a modified PECARN rule including the S100B protein assay. RESULTS: We included 1,062 children with mTBI (median age 4.5 years, sex ratio [F/M] 0.73) who were at intermediate risk for ciTBI: 494 (46.5%) during 2013-2014 and 568 (53.5%) during 2014-2015. During 2014-2015, S100B protein was measured in 451 (79.4%) children within 6 h after mTBI. The proportion of CT scans and in-hospital observations significantly decreased between the two periods, from 14.4 to 9.5% (p=0.02) and 73.9-40.5% (p<0.01), respectively. The number of CT scans performed to identify a single ciTBI was reduced by two-thirds, from 18 to 6 CT scans, between 2013-2014 and 2014-2015. All children with ciTBI were identified by the rules. CONCLUSIONS: The implementation of a modified PECARN rule including the S100B protein assay significantly decreased the proportion of CT scans and in-hospital observations for children with mTBI who were at intermediate risk for ciTBI.

Frequency of Extracorporeal Membrane Oxygenation Support and Outcomes After Implementation of a Structured PICU Network in Neonates and Children: A Prospective Population-Based Study in the West of France.

OBJECTIVES: To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers. DESIGN: Observational prospective population-based study from January 2015 to December 2019. PATIENTS: Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2-10‰]) and 35 newborns (9.4% [95% CI, 6.4-12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival. CONCLUSIONS: Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions.

Serum (1 → 3)-ß-D-glucan could be useful to rule out invasive candidiasis in neonates with an adapted cut-off.

AIM: We assessed the diagnostic accuracy of serum (1 â†’ 3)-ß-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC. METHODS: We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value. RESULTS: We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%). CONCLUSION: The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.

Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017.

BACKGROUND: The population structure of extraintestinal pathogenic Escherichia coli evolves over time, notably due to the emergence of antibiotic-resistant clones such as ESBL-producing Enterobacteriaceae (ESBL-E). OBJECTIVES: To analyse by WGS the genetic diversity of a large number of ESBL-E isolated from urinary tract infections in children from paediatric centres across France between 2014 and 2017 and collected by the National Observatory of febrile urinary tract infection (FUTI) caused by ESBL-E. METHODS: A total of 40 905 Enterobacteriaceae-positive urine cultures were identified. ESBL-E were found in 1983 samples (4.85%). WGS was performed on 251 ESBL-E causing FUTI. STs, core genome MLST (cgMLST), serotype, fimH allele, ESBL genes and presence of papGII key virulence factor were determined. RESULTS: E. coli and Klebsiella pneumoniae were found in 86.9% (218/251) and 11.2% (28/251) of cases, respectively. Several STs predominate among E. coli such as ST131, ST38, ST69, ST73, ST95, ST405, ST12 and ST1193, while no ST emerged in K. pneumoniae. E. coli ST131, ST38 and ST1193 increased during the study period, with a heterogeneity in papGII prevalence (64.5%, 35% and 20% respectively). Most isolates harboured the CTX-M type (97%) with a predominance of blaCTX-M-15. blaCTX-M-27, an emerging variant in E. coli, is found in various STs. cgMLST enabled discrimination of clusters within the main STs. CONCLUSIONS: The predominance of ST131, and the emergence of other STs such as ST38 and ST1193 combined with ESBL genes deserves close epidemiological surveillance considering their high threat in infectious disease. cgMLST could be a discriminant complementary tool for the analyses.

Epidemiology of Community-Onset Severe Bacterial Infections in Children and Its Evolution: A Population-Based Study in France.

OBJECTIVES: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. DESIGN: Prospective, observational, population-based study from 2009 to 2014. SETTING: An administrative area accounting for 13% of the French pediatric population. PATIENTS: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. CONCLUSIONS: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Evaluation of a Temporal Association between Vaccination and Subdural Hematoma in Infants.

OBJECTIVE: To investigate a temporal association between vaccination and subdural hematoma, the main feature of abusive head trauma. STUDY DESIGN: From a prospective population-based survey carried out in 1 administrative district in France between January 2015 and April 2017, including all infants between 11 and 52 weeks old who underwent a first cerebral imaging (computerized tomography scan or magnetic resonance imaging), we conducted a nested case-control study. Vaccine exposure was compared between cases (infants with subdural hematoma) and 2-3 paired controls, without subdural hematoma or any other imaging findings compatible with abusive head trauma. Cases and controls were matched on chronological (±7 days) and gestational (≤33 vs >33 weeks) ages, respectively. Vaccination status was collected in the personal national pediatric health booklet. RESULTS: Among the 228 prospectively surveyed infants, 28 had subdural hematoma including 22 with abusive head trauma. The mean chronological age at imaging was 5.3 months among the 28 cases and the 62 controls, who did not differ significantly in median time since last vaccination (1.4 vs 1.3 months, P = .62) or frequency of at least 1 vaccination since birth (86% vs 89%; matched-pairs OR 0.77, 95% CI 0.17-3.86) or within 7 days (0.94, 0.08-6.96), 14 days (0.70, 0.12-2.92), or 21 days (0.48, 0.08-1.98) before cerebral imaging. CONCLUSIONS: We found no significant temporal association between vaccination and subdural hematoma diagnosis, which must continue to be considered a red flag for abusive head trauma and child abuse.

Vaccine-preventable severe morbidity and mortality caused by meningococcus and pneumococcus: A population-based study in France.

BACKGROUND: In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines. METHODS: We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated. RESULTS: Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs. CONCLUSIONS: Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy.

Procalcitonin and C-reactive protein may help to detect invasive bacterial infections in children who have fever without source.

AIM: This study evaluated the epidemiology and performance of biomarkers for identifying bacterial infections in children who presented with fever without source. METHODS: We conducted a prospective cohort study in the paediatric department at the University Hospital of Nantes, France, in 2016. Children older than six days and younger than five years of age were included. RESULTS: A total of 1060 children (52.2% male) with fever without source were admitted, and the median age was 17 months (interquartile range: 6.6-24.3 months). Severe bacterial infections were diagnosed in 127 (11.9%) children and invasive bacterial infections in 11 (1.0%) children: four (0.3%) with bacterial meningitis and seven (0.6%) with bacteraemia. A further 114 (10.7%) had urinary tract infections. We explored the area under the receiver-operating characteristic curves for identifying invasive bacterial infections. The curves for procalcitonin and C-reactive protein assays were better than those for the absolute neutrophil counts and the white blood cell counts. CONCLUSION: This study found that there was a low prevalence of invasive bacterial infections in children who presented with fever without source. It also showed that procalcitonin and C-reactive protein may help to detect invasive bacterial infections in children who have fever without source.

Reporting studies on time to diagnosis: proposal of a guideline by an international panel (REST).

BACKGROUND: Studies on time to diagnosis are an increasing field of clinical research that may help to plan corrective actions and identify inequities in access to healthcare. Specific features of time to diagnosis studies, such as how participants were selected and how time to diagnosis was defined and measured, are poorly reported. The present study aims to derive a reporting guideline for studies on time to diagnosis. METHODS: Each item of a list previously used to evaluate the completeness of reporting of studies on time to diagnosis was independently evaluated by a core panel of international experts (n = 11) for relevance and readability before an open electronic discussion allowed consensus to be reached on a refined list. The list was then submitted with an explanatory document to first, last and/or corresponding authors (n = 98) of published systematic reviews on time to diagnosis (n = 45) for relevance and readability, and finally approved by the core expert panel. RESULTS: The refined reporting guideline consists of a 19-item checklist: six items are about the process of participant selection (with a suggested flowchart), six about the definition and measurement of time to diagnosis, and three about optional analyses of associations between time to diagnosis and participant characteristics and health outcomes. Of 24 responding authors of systematic reviews, more than 21 (≥88 %) rated the items as relevant, and more than 17 (≥70 %) as readable; 19 of 22 (86 %) authors stated that they would potentially use the reporting guideline in the future. CONCLUSIONS: We propose a reporting guideline (REST) that could help authors, reviewers, and editors of time to diagnosis study reports to improve the completeness and the accuracy of their reporting.

Compliance with the current recommendations for prescribing antibiotics for paediatric community-acquired pneumonia is improving: data from a prospective study in a French network.

BACKGROUND: Lower respiratory tract infection is a common cause of consultation and antibiotic prescription in paediatric practice. The misuse of antibiotics is a major cause of the emergence of multidrug-resistant bacteria. The aim of this study was to evaluate the frequency, changes over time, and determinants of non-compliance with antibiotic prescription recommendations for children admitted in paediatric emergency department (PED) with community-acquired pneumonia (CAP). METHODS: We conducted a prospective two-period study using data from the French pneumonia network that included all children with CAP, aged one month to 15 years old, admitted to one of the ten participating paediatric emergency departments. In the first period, data from children included in all ten centres were analysed. In the second period, we analysed children in three centers for which we collected additional data. Two experts assessed compliance with the current French recommendations. Independent determinants of non-compliance were evaluated using a logistic regression model. The frequency of non-compliance was compared between the two periods for the same centres in univariate analysis, after adjustment for confounding factors. RESULTS: A total of 3034 children were included during the first period (from May 2009 to May 2011) and 293 in the second period (from January to July 2012). Median ages were 3.0 years [1.4-5] in the first period and 3.6 years in the second period. The main reasons for non-compliance were the improper use of broad-spectrum antibiotics or combinations of antibiotics. Factors that were independently associated with non-compliance with recommendations were younger age, presence of risk factors for pneumococcal infection, and hospitalization. We also observed significant differences in compliance between the treatment centres during the first period. The frequency of non-compliance significantly decreased from 48 to 18.8 % between 2009 and 2012. The association between period and non-compliance remained statistically significant after adjustment for confounding factors. Amoxicillin was prescribed as the sole therapy significantly more frequently in the second period (71 % vs. 54.2 %, p < 0.001). CONCLUSIONS: We observed a significant increase in the compliance with recommendations, with a reduction in the prescription of broad-spectrum antibiotics, efforts to improve antibiotic prescriptions must continue.

What is new in neonatal infection?

Diagnostic of early neonatal infection remains a serious challenge. Since clinical symptoms and biological markers are neither sensitive nor specific, a lot of newborns suspected of infection, undergo biological analysis and empirical antibiotic treatment awaiting bacteriological results. However the prevalence of the disease has dramatically decreased since the last twenty years, subsequently to the generalization of the per partum antibioprophylaxis strategy. Because the possible deleterious effects of neonatal antibiotic treatment are well described now, it appears very urgent to restrict their use to the infected newborns only. Recent studies underline the benefit of using procalcitonin (PCT) to diferentiate virai infections of bacterial infections. PCT in blood cord could become a new and efficient marker to help neonatologists taking care of infection-suspected newborns. An evidence based approach is necessary, combining anamnestic, clinical and biological data as PCT to identify the very low risk newborns population and to limit the neonatal antibiotic prescriptions.

Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants.

INTRODUCTION: Vancomycin is the usual antibiotic treatment in coagulase-negative staphylococcus sepsis in premature infants but causes renal toxicity. As linezolid is effective in Gram-positive cocci infection, and devoid of renal side-effects, it has been used in Nantes neonatal intensive care units and linezolid plasma concentrations were monitored. AIM: The aims of this study are to report data on linezolid concentrations in premature infants, describe clinical and bacteriological evolution during treatment, and determine potential side effects. METHODS: A retrospective observational study of premature infants treated with linezolid in Nantes Hospital from January 2008 through November 2011 was conducted. Linezolid plasma concentrations, possible side effects due to linezolid, and clinical response to linezolid treatment were collected from folder review. RESULTS: Twenty-four linezolid plasma concentrations were monitored in 16 premature patients, at steady state for continuous intravenous administration or 7 ± 1.5 h after last oral administration. Except for one case, linezolid plasma concentrations were ≥minimal inhibition concentration (MIC) for linezolid for both parenteral and oral administrations. We observed three cases of thrombocytopenia, two of leukopenia, three of neutropenia, and one of severe hyperlactacidemia, resolving after discontinuation of treatment. Clinical signs of infection resolved in 13/16 cases. Bacteria were coagulase-negative Staphylococci in 12/16 cases and were eradicated in 9/12 evaluable cases. CONCLUSIONS: This study reports an adequate linezolid plasma concentration with regard to the linezolid MIC in extremely premature infants. However, considering adverse events reported, its use should be cautious and may concern only oral administration during the late phase of infection, to limit paradoxical catheter use to treat nosocomial infections. Moreover, safe and efficient anti-Staphylococcus therapies should be identified to treat this vulnerable population.