Christèle Gras-Le Guen

Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.

The use of procalcitonin in the diagnosis of late-onset infection in neonatal intensive care unit patients

We evaluated the semi-quantitative procalcitonin level for diagnosing late-onset infections in 176 neonates. Using a cut-off level of 0.5ng/ml, the sensitivity was 84.4%±0.19, specificity was 93.9%±0.04, positive predictive value was 82.6%±0.1, and negative predictive value was 94.6%±0.04. Procalcitonin could be a useful marker of late-onset infection in neonates.

Therapeutic amoxicillin levels achieved with oral administration in term neonates

AimsThe standard treatment of neonatal group B Streptococcus infection is intravenous amoxicillin for 10xa0days. We investigated whether effective serum amoxicillin concentrations could be reached by switching to oral amoxicillin after 48xa0h of intravenous administration in full-term neonates with group B Streptococcus infection.MethodsOver 2xa0years, we included 222 full-term neonates who had early onset group B streptococcal disease responsive to 48xa0h of intravenous amoxicillin, at which point they were asymptomatic and fed orally. They were switched to oral amoxicillin (300 or 200xa0mg/kg per day in four divided doses). Steady-state serum amoxicillin concentrations were determined 48xa0h later by high-performance liquid chromatography; values ≥5xa0mg/l were considered effective.ResultsMean gestational age was 39.32u2009±u20091.5xa0weeks ,and mean birth weight was 3,422u2009±u2009533xa0g; 29 newborns were bacteremic. Median serum amoxicillin concentration on oral therapy was 31,.15 (range 11–118) and 25.80 (range 5–84.8) with 300 and 200xa0mg/kg per day, respectively. None of the infants had a concentration <5xa0mg/l (pu2009<u20090.001). Gastrointestinal tolerance was satisfactory; 216 patients were discharged at 5xa0days of age, and none was readmitted within the 3-month follow-up.ConclusionEarly switching to the oral route in asymptomatic full-term newborns with early onset group B streptococcal disease maintained serum amoxicillin concentrations within our predefined therapeutic range (error risk<0.001). This strategy may hold potential for reducing treatment invasiveness and shortening hospital length of stay.

Effectiveness of linezolid and imipenem association in the treatment of severe community-acquired pneumonia in children: Two case reports

Two children with severe pneumonia, purulent pleural effusions, and abscess formation unresponsive to appropriate antibiotic therapy recovered promptly after the introduction of linezolid and imipenem association. Linezolid is a new antibiotic with high bioavailability and an outstanding safety profile, synergistic with imipenem, which may deserve a place in the armamentarium for severe pneumonia in children

Simulation of human gentamicin pharmacokinetics in an experimental Enterococcus faecalis endocarditis model.

ABSTRACT Significant differences between animal and human pharmacokinetics may be responsible for the conflicting results of experimental studies. This study determined the impact of human pharmacokinetic simulation (HPS) on gentamicin activity in an Enterococcus faecalis endocarditis model. The decrease in bacterial counts was greater with HPS than with a dose-equivalent regimen without HPS.

Electrochemical skin conductance for quantitative assessment of sweat function: Normative values in children

Highlights • Sudomotor function can be assessed through the measurement of electrochemical skin conductance using the Sudoscan system.• This test is easily done in children and normative data are provided.• It can be helpful in case of small fibre neuropathy in children.

Immunological characterization of a rat model of Duchenne\'s disease and demonstration of improved muscle strength after anti-CD45RC antibody treatment.

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats (Dmdmdx) that closely reproduce the phenotype of DMD patients. Dmdmdx rats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4+ and CD8+ expressing high levels of CD45RChigh cells. Treatment of young Dmdmdx rats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RChigh T cells with no obvious side-effects. Prednisolone treatment of Dmdmdx rats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RChigh cells but resulted in severe weight loss. Overall, Dmdmdx rats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength in Dmdmdx rats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.

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

BACKGROUNDnIn 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.nnnMETHODSnWe conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1xa0month to 16xa0years 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.nnnRESULTSnAmong the 124 children with serotyped meningococcal (nxa0=xa075) or pneumococcal (nxa0=xa049) severe infections included (median age 26xa0months), 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.nnnCONCLUSIONSnMortality 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.

The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol

Introduction Even after ‘back-to-sleep’ campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1u2009month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area. Methods and analysis This observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths. Ethics and dissemination The French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l’Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d’Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.

Reference ranges for serum S100B neuroprotein specific to infants under four months of age

BACKGROUNDnMinor head traumatisms are a common reason for consultation in paediatric emergency departments. The diagnosis of traumatic brain injuries involves performing a cranial computed tomography (CCT), associated with a risk of cancer due to the radiation. The serum S100B is an effective biomarker used to reduce reliance on CCT. While reference ranges have been determined, the limited number of cases regarding infants less than 4months of age has not allowed this biomarker to be used with this age group. Our study aimed to determine reference ranges for serum S100B based on a larger number of infants from birth to 4months of age.nnnMETHODSnThree centres included infants coming to the hospital for whom blood samples were taken. These samples were analysed to determine the upper reference values based on the 95th percentile.nnnRESULTSn135 samples were analysed. The upper reference value was 0.51μg/L for children aged 0 to 4months. There was no effect of the gender.nnnCONCLUSIONSnThis study provides serum S100B reference ranges based on the largest group of neurologically healthy 0 to 4-month-old infants analysed to date. Reliable reference values of S100B for children are now determined. It is the first step towards validation of thresholds for studies integrating S100B into a clinical decision rule for MHT in children.