Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow.

BACKGROUND: In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. METHODS: A total of 3 QCs were implemented and processed through the whole mNGS workflow: a no-template-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7). RESULTS: The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6 to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses). CONCLUSIONS: Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.

Atypical Exciton-Phonon Interactions in WS2 and WSe2 Monolayers Revealed by Resonance Raman Spectroscopy.

Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first-optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic).

Temperature dependence of the electronic structure of semiconductors and insulators.

The renormalization of electronic eigenenergies due to electron-phonon coupling (temperature dependence and zero-point motion effect) is sizable in many materials with light atoms. This effect, often neglected in ab initio calculations, can be computed using the perturbation-based Allen-Heine-Cardona theory in the adiabatic or non-adiabatic harmonic approximation. After a short description of the recent progresses in this field and a brief overview of the theory, we focus on the issue of phonon wavevector sampling convergence, until now poorly understood. Indeed, the renormalization is obtained numerically through a slowly converging q-point integration. For non-zero Born effective charges, we show that a divergence appears in the electron-phonon matrix elements at q → Γ, leading to a divergence of the adiabatic renormalization at band extrema. This problem is exacerbated by the slow convergence of Born effective charges with electronic wavevector sampling, which leaves residual Born effective charges in ab initio calculations on materials that are physically devoid of such charges. Here, we propose a solution that improves this convergence. However, for materials where Born effective charges are physically non-zero, the divergence of the renormalization indicates a breakdown of the adiabatic harmonic approximation, which we assess here by switching to the non-adiabatic harmonic approximation. Also, we study the convergence behavior of the renormalization and develop reliable extrapolation schemes to obtain the converged results. Finally, the adiabatic and non-adiabatic theories, with corrections for the slow Born effective charge convergence problem (and the associated divergence) are applied to the study of five semiconductors and insulators: α-AlN, ß-AlN, BN, diamond, and silicon. For these five materials, we present the zero-point renormalization, temperature dependence, phonon-induced lifetime broadening, and the renormalized electronic band structure.

Early impact of 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in children.

BACKGROUND: Pneumococcal serotypes 1, 3, 5, 7F, and 19A were the most implicated in community-acquired pneumonia (CAP) after implementation of 7-valent pneumococcal conjugate vaccine (PCV7). In France, the switch from PCV7 to 13-valent pneumococcal conjugate vaccine (PCV13) occurred in June 2010. An active surveillance network was set up to analyze the impact of PCV13 on CAP. METHODS: An observational prospective study performed in 8 pediatric emergency departments from June 2009 to May 2012 included all children between 1 month and 15 years of age with chest radiography-confirmed pneumonia. Three 1-year periods were defined: pre-PCV13, transitional, and post-PCV13. RESULTS: During the 3-year study period, among the 953 274 pediatric emergency visits, 5645 children with CAP were included. CAP with pleural effusion and documented pneumococcal CAP were diagnosed in 365 and 136 patients, respectively. Despite an increase (4.5%) in number of pediatric emergency visits, cases of CAP decreased by 16% (2060 to 1725) between pre- and post-PCV13 periods. The decrease reached 32% in infants in the same periods (757 to 516; P < .001). Between pre- and post-PCV13 periods, the proportion of CAP patients with a C-reactive protein level >120 mg/dL decreased from 41.3% to 29.7% (P < .001), the number of pleural effusion cases decreased by 53% (167 to 79; P < .001) and the number of pneumococcal CAP cases decreased by 63% (64 to 24; P = .002). The number of additional PCV13 serotypes identified decreased by 74% (27 to 7). CONCLUSIONS: Our data suggest a strong impact of PCV13 on CAP, pleural effusion, and documented pneumococcal pneumonia, particularly cases due to PCV13 serotypes.

SPILF update on bacterial arthritis in adults and children.

In 2020 the French Society of Rhumatology (SFR) published an update of the 1990 recommendations for management of bacterial arthritis in adults. While we (French ID Society, SPILF) totally endorse this update, we wished to provide further information about specific antibiotic treatments. The present update focuses on antibiotics with good distribution in bone and joint. It is important to monitor their dosage, which should be maximized according to PK/PD parameters. Dosages proposed in this update are high, with the optimized mode of administration for intravenous betalactams (continuous or intermittent infusion). We give tools for the best dosage adaptation to conditions such as obesity or renal insufficiency. In case of enterobacter infection, with an antibiogram result "susceptible for high dosage", we recommend the requesting of specialized advice from an ID physician. More often than not, it is possible to prescribe antibiotics via the oral route as soon as blood cultures are sterile and clinical have symptoms shown improvement. Duration of antibiotic treatment is 6 weeks for Staphylococcus aureus, and 4 weeks for the other bacteria (except for Neisseria: 7 days).

Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review.

Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.

A report on the large measles outbreak in Lyon, France, 2010 to 2011.

In 2010 and 2011, the city of Lyon, located in the Rhône-Alpes region (France), has experienced one of the highest incidences of measles in Europe. We describe a measles outbreak in the Lyon area, where cases were diagnosed at Lyon University hospitals (LUH) between 2010 and mid-2011. Data were collected from the mandatory notification system of the regional public health agency, and from the virology department of the LUH. All patients and healthcare workers who had contracted measles were included. Overall, 407 cases were diagnosed, with children of less than one year of age accounting for the highest proportion (n=129, 32%), followed by individuals between 17 and 29 years-old (n=126, 31%). Of the total cases, 72 (18%) had complications. The proportions of patients and healthcare workers who were not immune to measles were higher among those aged up to 30 years. Consequently, women of childbearing age constituted a specific population at high risk to contract measles and during this outbreak, 13 cases of measles, seven under 30 years-old, were identified among pregnant women. This study highlights the importance of being vaccinated with two doses of measles vaccine, the only measure which could prevent and allow elimination of the disease.

Respiratory viruses in children admitted to hospital intensive care units: evaluating the CLART® Pneumovir DNA array.

Viruses play a significant part in children's respiratory infections, sometimes leading to hospitalization in cases of severe respiratory distress. The aim of this study was to investigate respiratory infections in children treated in a hospital intensive care unit (ICU). Assays were performed using the CLART® Pneumovir DNA array assay (Genomica, Coslada, Madrid, Spain), which makes it possible to detect 11 genus of respiratory viruses simultaneously. During the winter of 2008-2009, 73 respiratory specimens collected from 53 children under 2 years of age and admitted to an ICU were tested. At least one virus was detected in 78% (57/73) of the samples. The virological diagnosis was based on single infections in 65% (37/57) and on multiple infections in 35% (20/57) of cases. The array assay revealed respiratory syncytial virus (RSV) in 73.6% (42/57) of the samples and rhinovirus in 24.6% (14/57), either on their own or in co-infections. All viruses identified in single and multiple infections were tested, taking into account clinical features, risk factors, and severity criteria. Children with no risk factors presented more multiple infections, up to 42% of cases, than children with at least one risk factor. RSV seemed to induce severe symptoms by itself as no difference in intubation needs was observed when RSV was detected on its own or in co-infection. The CLART® Pneumovir DNA array was useful for examining severe viral respiratory infections, when other viruses than those detected by conventional methods could be involved, particularly in an ICU.

[Active drug monitoring of adverse drug reactions in pediatric emergency department]. / Recueil systématique et actif des évènements indésirables médicamenteux chez les enfants admis aux urgences pédiatriques.

OBJECTIVES: The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period. METHOD: The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated. RESULTS: During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations. CONCLUSIONS: Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.

Otorhinolaryngological manifestations and delayed diagnosis in Kawasaki disease.

OBJECTIVES: Kawasaki disease (KD) is a febrile multisystemic vasculitis of unknown etiology whose coronary prognosis is improved by early diagnosis and management. The objective of this study was to describe ENT manifestations encountered and to look for a delayed diagnosis associated with these manifestations. METHODS: A retrospective descriptive single-center study was conducted in Lyon between January 2009 and December 2017. All children treated for Kawasaki disease were included in the study. Clinical, biological and cardiac ultrasound data were collected. According to the diagnosis made at the first medical visit, children were classified into two groups: diagnosis of ENT spectrum or non-ENT diagnosis. The diagnostic times were compared by a Student test. RESULTS: 142 patients were included: 64 in the ENT diagnostic group, 78 in the non-ENT diagnostic group. When the initial diagnosis was of ENT spectrum, the diagnostic time of KD was significantly longer: 8.51 days vs 5.77 days - (p < 0.01). The total duration of fever was also longer - 10.92 vs 8.32 days - (p = 0.013) - and the frequency of antibiotics intake more important - 92.2% vs 46.2% - (p < 0.01). Four children underwent surgery in the ENT diagnostic group: two retro-pharyngeal abscesses, one paracentesis and one cervicectomy. CONCLUSIONS: ENT manifestations are frequently at the forefront of KD and constitute a misleading clinical picture responsible for delayed diagnosis and potentially inappropriate medico-surgical management. It is necessary to provide more education to practitioners for earlier recognition of Kawasaki disease.

[Managing children skin and soft tissue infections]. / Propositions thérapeutiques pour le traitement des infections cutanées bactériennes.

The skin infections are common in pediatrics, ranging from furonculosis or impetigo to the severe forms of necrotizing dermohypodermitis. The general antibiotic treatments are not always indicated but when they are, they must take into account the resistance of two main species of bacteria (Staphylococcus aureus and Streptococcus pyogenes), the pharmacokinetics-pharmacodynamic parameters and the severity and type of infection. Two situations should be treated by topical treatements: limited impetigo and furonculosis. The two topical antibiotics used preferentially are mupirocine and fucidic acid. Soon, a third topical antibiotic, reptamuline will complete these. For uncomplicated superficial skin infections justifying an oral antibiotic, amoxicillin-clavulanate offers the best guarantee of efficiency. Poor pharmacodynamic-pharmacokinetic must lead to not prescribe oral M penicillins. In case of allergy, a first-generation cephalosporin, a macrolide (if the susceptibility of the strain was checked) or pristinamycine (after 6 years of age) are acceptable alternatives. For dermohypodermitis bacterial antibiotic of choice remains amoxicillin-clavulanate through IV route, to be active against S. pyogenes but also S. aureus and anaerobic bacteria. The IV route is maintained until regression general signs and a relay orally by the same drug is then possible. For toxinic syndromes and necrozing fascitis clindamycin should be added to a beta-lactam because of its action on protein synthesis in particular reducing the toxins production.

[Acute hemiparesis revealing a neuroborreliosis in a child]. / Hémiparésie aiguë révélatrice d'une neuroborréliose chronique chez un enfant.

We report on a 11-year-old boy who had 2 acute hemiparesis episodes over a period of 1 month. He suffered from headache and fatigue since 1 year. He could not remember neither a tick bite nor a local erythematous skin lesion. The diagnosis of neuroborreliosis was based on intrathecal production of specifics antibodies. Furthermore, the CSF/blood glucose ratio was decreased (0.14), which was rarely described. Cranial MRI showed left capsulothalamic inflammation and a vasculitis. The patient was successfully treated by ceftriaxone. Neuroborreliosis should be considered in all children with stroke-like episode, even in the absence of a history of a tick bite.

[Analysis of delayed cerebrospinal fluid sterilization of pneumococcal meningitis in children]. / Stérilisations retardées du liquide céphalorachidien au cours des méningites à pneumocoque de l'enfant.

OBJECTIVE: Delayed cerebrospinal fluid sterilization is defined by a positive second lumbar puncture, recommanded according to the guidelines from the French Consensus Conference of 1996 between the 36th and 48th hours after the beginning of antibiotics prescribed for pneumococcal meningitis. The aim of this study was to analyze specifically delayed cerebrospinal fluid sterilization, identified during the first 5 years of the French observatory of children bacterial meningitis. PATIENTS AND METHODS: The Groupe de Pathologie Infectieuse Pédiatrique (GPIP) and Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV) has set up since the first of January 2001 a descriptive national multicenter network, to determine incidence, main characteristics, and prognosis of bacterial meningitis in children. A questionnaire, available in all paediatric unit taking care of bacterial meningitis, was completed by a referral doctor. It contained reasons for inclusion in the study, anamnesis, clinical examination, treatment, pneumococcal characteristics, and short term prognosis. Delayed cerebrospinal fluid sterilization were identified, and the analysis of their medical records completed the questionnaire. RESULTS: From 1st January 2001 to 31 December 2005, 616 pneumococcal meningitis were identified. Among them, 442 had a second lumbar puncture, and 8 had delayed cerebrospinal fluid sterilization. The analyis of their medical records were reviewed to describe their characteristics. Two had an osteomeningeal breach, one a ventriculoperitoneal valve. All received previously an antibiotic, and were treated with a curative antibiotic by cephalosporins. Vancomycin was given in 6 cases. The antibiotic was inadapted to the French guidelines for 1 patient. There are 4 vaccine type pneumococci and only 1 strain was resistant to penicillin, and intermediate to cephalosporins. The controlled lumbar puncture was made between 36.5 and 179.4hours after beginning antibiotics. One patient has received a double dose of steroids. Three were in a coma, had convulsions, and were ventilated, none died. One patient has a sequellar paired deafness, two a severe disability, four a normal psychomotor development. CONCLUSION: The delay of sterilization is a rare situation and represented only 1.8 % of pneumococcal meningitis during the first five years of the observatory. These results suggest that a second lumbar puncture to assess sterilization could be proposed only in cases of unfavourable clinical course, MIC greater than or equal 0.5mg/l to 3GC, risk factors for delayed cerebrospinal fluid sterilization and high bacterial inoculum.

Slug/Pcad pathway controls epithelial cell dynamics in mammary gland and breast carcinoma.

Mammary gland morphogenesis results from the coordination of proliferation, cohort migration, apoptosis and stem/progenitor cell dynamics. We showed earlier that the transcription repressor Slug is involved in these functions during mammary tubulogenesis. Slug is expressed by a subpopulation of basal epithelial cells, co-expressed with P-cadherin (Pcad). Slug-knockout mammary glands showed excessive branching, similarly to Pcad-knockout. Here, we found that Slug unexpectedly binds and activates Pcad promoter through E-boxes, inducing Pcad expression. We determined that Pcad can mediate several functions of Slug: Pcad promoted clonal mammosphere growth, basal epithelial differentiation, cell-cell dissociation and cell migration, rescuing Slug depletion. Pcad also promoted cell migration in isolated cells, in association with Src activation, focal adhesion reorganization and cell polarization. Pcad, similarly to Slug, was required for in vitro 3D tubulogenesis. Therefore, Pcad appears to be responsible for epithelial-mesenchymal transition-linked plasticity in mammary epithelial cells. In addition, we found that genes from the Slug/Pcad pathway components were co-expressed and specifically correlated in human breast carcinomas subtypes, carrying pathophysiological significance.

Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth.

Transplantation of bone marrow mesenchymal stem cells (BMDCs) into a denervated side of the spinal cord was reported to be a useful option for axonal regeneration. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. Cultured reassociations between dissociated embryonic dental mesenchymal and epithelial cells and implantation lead to a vascularized tooth organ regeneration. However, when reassociations were coimplanted with a trigeminal ganglion (TG), innervation did not occur. On the other hand, reassociations between mixed embryonic dental mesenchymal cells and bone marrow-derived cells isolated from green fluorescent protein (GFP) transgenic mice (BMDCs-GFP) (50/50) with an intact and competent dental epithelium (ED14) were innervated. In the present study, we verified the stemness of isolated BMDCs, confirmed their potential role in the innervation of bioengineered teeth, and analyzed the mechanisms by which this innervation can occur. For that purpose, reassociations between mixed embryonic dental mesenchymal cells and BMDCs-GFP with an intact and competent dental epithelium were cultured and coimplanted subcutaneously with a TG for 2 wk in ICR mice. Axons entered the dental pulp and reached the odontoblast layer. BMDCs-GFP were detected at the base of the tooth, with some being present in the pulp associated with the axons. Thus, while having a very limited contribution in tooth formation, they promoted the innervation of the bioengineered teeth. Using quantitative reverse transcription polymerase chain reaction and immunostainings, BMDCs were shown to promote innervation by 2 mechanisms: 1) via immunomodulation by reducing the number of T lymphocytes (CD3+, CD25+) in the implants and 2) by expressing neurotrophic factors such as NGF, BDNF, and NT3 for axonal growth. This strategy using autologous mesenchymal cells coming from bone marrow could be used to innervate bioengineered teeth without treatment with an immunosuppressor such as cyclosporine A (CsA), thus avoiding multiple side effects.

[Osteoarticular infections with staphylococcus aureus secreting Panton-Valentine leucocidin]. / Infections ostéoarticulaires à staphylocoques dorés sécréteurs de la leucocidine de Panton-Valentine.

Panton-Valentine Leucocidin (PVL) is associated in the USA with community-acquired meticillin resistant strains of Staphylococcus aureus (CA-MRSA). Bone and joint infection due to such strains appears to be more severe, necessiting longer antibiotic course and various surgical procedure. Our study of 14 PVL positive bone and joint infection, performed in France where PVL is rarely (2/14) associated with meticillin resistance, demonstrates that severity is linked with PVL secretion more than with resistance. Considering PVL associated bone and joint infections as a toxin-mediated disease, prompt diagnosis is needed in order to start specific therapeutic procedures. PVL mediated infection could be evoked in front of severe acute osteomyelitis or arthritis, with radiological abnormalities present in the first days of evolution and with pejorative evolution despite antibiotic treatment. Evolution toward multifocal osteomyelitis and/or multiple abscesses seems to be a major characteristic of such infection. Therapeutic approach should use an association of parenteral antibiotics with at least one molecule active against protein synthesis like Clindamycin, associated with betalactams or Vancomycin in area of high incidence of CA-MRSA. Surgical procedure should be considered whenever focal abscesses of bones or adjacent tissue is detected and should be repeated in most cases.

[Awareness and application of vaccine recommendations for chickenpox in French Nurse Schools]. / Connaissance et application des recommandations vaccinales concernant la varicelle en institut de soins infirmiers en France.

Since 2004, the French High Committee on Public Hygiene has recommended chickenpox vaccination for first-year medical or paramedical students with no history of chickenpox and with negative serology. A survey was carried out among directors of nurse schools to evaluate both their awareness of these new recommendations and the way in which they had been applied. A questionnaire was sent by mail to each of the directors of the 332 nurse schools identified throughout France. Less than half (41%) of the 147 directors who responded said they were aware of recommendations, and 31% stated they had real knowledge of the recommendations. Only 21% enquire about chickenpox history of students enrolling in their school, and 9% undertake serological assessment of students with no known history of varicella or zoster. More needs to be done both to inform nurse school directors of the vaccine recommendations and to ensure their application.

Antimicrobial treatment of infrequent bacterial species isolated in children.

This section summarizes the empirical antimicrobial treatment according to the less frequent bacterial species responsible for infection whether community-acquired or nosocomial. It specifies their role in diseases and the recommended antibiotics, taking into account their natural and most common acquired resistance and the pharmacokinetic-pharmacodynamic parameters. The advice of an infectious disease specialist or bacteriologist is recommended.

Antibiotic treatment of lower respiratory tract infections.

Lower respiratory tract infections, i.e., bronchitis, bronchiolitis, and pneumonia, are the second leading cause of antibiotic prescriptions. The vast majority of these infections are due to viruses and are self-limited diseases: most patients recover spontaneously. These two facts explain that antibiotic prescriptions must be limited to some clinical situations for which the diagnosis has to be done early. The first message of this manuscript is to strengthen non-antibiotic prescriptions in many situations such as bronchitis and bronchiolitis. Implementation of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of pneumonia and empyema, and induced a dramatic decrease in the proportion of pneumococcus in these diseases. However, pneumococcus remains probably the leading cause of bacterial pneumonia and empyema and the main target of antibiotic treatment. Furthermore, the implementation of PCVs has reduced resistance to antibiotics including penicillins and macrolides antibiotics, explaining the de-escalation proposed in the last few years, with the reduction of the use if third generation cephalosporins and vancomycin. The therapeutic choices proposed in this article follow the previous official guidelines in France. Serious infections represented by empyema and severe pneumonia remain therapeutic emergencies, most often warranting hospitalization and IV antibiotics.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequent documented bacterial infections in children. The antibiotic choices proposed in this manuscript are based on the guidelines published by the Pediatric Infectious Disease Group (GPIP) and the French-Language Infectious Disease Society (SPILF). Dipstick positive for leukocytes and/or nitrites must precede in most circumstances (excluding the newborns, neutropenic patients and those with sepsis), urine culture and antibiotic prescription. The proportion of extended-spectrum ß-lactamase (ESBL) Escherichia coli strains has increased steadily in recent years, and the situations in which oral antibiotic switch is frequently not available are increasing. Cephalosporin resistance remains below 10% in most regions of France. However, there is no doubt that the proportion of resistant strains will increase in the coming years: the only uncertainly concerns the speed of this trend. With the aim of saving penems and promoting outpatient care, this guide proposes among the acceptable initial treatments for febrile urinary tract infections in infants, amikacin. This aminoglycoside remains active against the majority of ESBL strains and can be prescribed in once-daily dose allowing also ambulatory management of patients from pediatric emergency department.