Severe atypical Lemierre syndrome caused by methicillin-sensitive Staphylococcus aureus: Two pediatric case reports.

BACKGROUND: Lemierre syndrome is typically associated with ear, nose, and throat (ENT) infections caused by Fusobacterium necrophorum. Since 2002, cases of atypical Lemierre-like syndrome secondary to Staphylococcus aureus have been reported. CASES: We report two pediatric cases of atypical Lemierre syndrome with a similar presentation: exophthalmia, absence of pharyngitis, metastatic lung infection, and intracranial venous sinus thrombosis. Both patients had a favorable outcome following treatment with antibiotics, anticoagulation, and corticosteroids. CONCLUSION: Regular therapeutic monitoring of antibiotic levels helped to optimize antimicrobial treatment in both cases.

Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Infant botulism: Report of a misleading case and important key messages.

Infant botulism is a rare and life-threatening disease caused by the inhalation of Clostridium botulinum spores and differs from adult forms. We report the case of infant botulism in a 4-month-old boy who was exclusively breastfed without any consumption of honey. He presented with severe and acute encephalo-myelo-radiculitis. The patient was treated without success for suspected "postviral" central nervous system inflammatory disease. The diagnosis was eventually made 20 days after the onset of symptoms on the basis of a stool sample. Recovery was complete. Infant botulism should be suspected when infants present with acute flaccid paralysis or brainstem weakness and specific immunoglobulins should be administered.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

The challenging management of a series of 43 infants with Netherton syndrome: unexpected complications and novel mutations.

BACKGROUND: Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging. OBJECTIVES: To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management. METHODS: We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data. RESULTS: A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion. CONCLUSIONS: Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience.

Severe and fatal forms of COVID-19 in children.

OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

[Evaluation of pre-travel prevention and morbidity in child travelers]. / Enquêtes auprès des familles d'enfants voyageurs : évaluation des conseils de prévention et prévalence des maladies rencontrées lors d'un séjour hors d'Europe.

UNLABELLED: International travel is growing, but few data exist on prevention for children traveling. The aim of this study was to describe a population of children traveling from France to countries outside Europe and to evaluate the quality of prevention and healthcare services provided for these travelers. MATERIALS AND METHODS: We conducted a retrospective epidemiological study in three pediatric emergency departments in Paris from August to October 2009 and 2012. Data were collected retrospectively from anonymous questionnaires proposed to families consulting emergency services, irrespective of their reason, who had recently traveled (in the year preceding travel outside the European Union). RESULTS: Of the 166 children included, who for the most part had traveled to visit relatives and friends in Sub-Saharan Africa and North Africa, 76% of their families were from the destination countries, 78% had received prevention counseling, mostly with their doctor. They had been vaccinated against yellow fever, but the hepatitis A vaccine was neglected. The preventive measures had been difficult to achieve in practice. During travel, 54% of children had health problems (39% diarrhea, 29% vomiting, 31% fever) prompting medical care in 28%, 5% were admitted to a hospital, and 4% had return to France earlier than planned. In epidemic areas, 13% of children had malaria. CONCLUSION: There is poor counseling on basic prevention (hygiene, diarrhea, malaria, immunization). Time constraints in pediatricians and competing priorities could explain this problem. The challenge for healthcare providers to reduce these pathologies is to provide services of sufficient quality and clarity. All medical stakeholders have an important role to play.

[Pregnancy in patients with a history of ischaemic heart disease - Case series and literature review]. / Grossesse chez les patientes ayant un antécédent de cardiopathie ischémique - Série de cas et revue de la littérature.

Heart diseases complicate 1 to 3% of pregnancies and are the leading cause of indirect maternal deaths. Prior ischaemic heart event in pregnant patients is increasing. Most knowledge is based on few reports and there are no French nor international recommendations about the specific management of these patients. The specificity of the management of these patients during pregnancy, delivery and post-partum depends on the severity of the prior cardiac event and its consequences. This will be illustrated by the report of four recent cases managed in our hospital. First patient had myocardial infarction with normal left ventricular ejection fraction (LVEF). Second patient had a Tako-Tsubo syndrome with LVEF 45%. Third patient had ischemic cardiopathy with LVEF 30%. Fourth patient had myocardial infarction with LVEF 20%. A multidisciplinary follow-up should be required, especially in patients with severe ventricular dysfunction. The risk of fetal growth restriction appears to be increased, suggesting that closer ultrasound monitoring is necessary.

[Superficial skin infections and bacterial dermohypodermitis]. / Infections superficielles de la peau et dermo-hypodermites bactériennes.

Staphylococcus aureus and Streptococcus pyogenes are the two main bacteria involved in skin infections in children. Mild infections like limited impetigo and furonculosis should preferentially be treated by topical antibiotics (mupirocine or fucidic acid). Empiric antimicrobial therapy of dermohypodermitis consists in amoxicillin-clavulanate through oral route (80 mg/kg/d) or parenteral route (150 mg/kg amoxicillin per d. in 3-4 doses) for complicated features: risk factors of extension of the infection, sepsis or fast evolution. Clindamycin (40 mg/kg/d per d. in 3 doses) should be added to the beta-lactam treatment in case of toxinic shock, surgical necrotizing soft tissues or fasciitis infections.

[Antibiotic prophylaxis in visceral and urologic pædiatric surgery]. / Antibioprophylaxie peropératoire pour la chirurgie viscérale et urologique en pédiatrie.

Surgical site infections are the leading cause of perioperative morbidity and mortality as well as increased costs following surgery. Among preventive measures, antibiotic prophylaxis significantly decreases this risk. Adult guidelines have recently been published. Specific pædiatric data are scarce, but adult recommendations can be used by extrapolation except for the neonates. For procedures that may warrant antimicrobial prophylaxis, agents of choice are first-generation cephalosporins who are not currently used in curative treatment, like cefazolin, with an appropriate dosing. A single perioperative dose of antibiotics is often sufficient. Continuation for more than 24 hours is rarely advised.

Impact of travel on the seroprevalence of hepatitis A in children.

BACKGROUND: Recent data about hepatitis A virus (HAV) seroprevalence in industrialized countries and the impact of travels to endemic areas are sparse or absent, particularly for children. OBJECTIVE: To determine the impact of travel to endemic areas on HAV seroprevalence and estimate the overall HAV seroprevalence in children in France. To identify risk factors for positive HAV serologic results. STUDY DESIGN: This prospective multicentre cross-sectional seroprevalence study took place in eight paediatric emergency units throughout France. Children 1-16 years of age following all inclusion and exclusion criteria were included. Demographic, socioeconomic, and travel data were prospectively collected with a standardized questionnaire before measurement of specific HAV antibodies. HAV seroprevalence was determined and its association with diverse variables assessed by univariate and multivariate analyses. RESULTS: 430 children were included, of whom 116 had travelled to endemic areas. The HAV seroprevalence in the overall population was 5% (95%CI, 3-7) and was higher among the travellers (12% [95%CI, 6-18]) than among the others (2% [95%CI, 0-3]), OR=7.0 [95%CI, 2.6-18.8]. Risk factors identified for positive serologic results for HAV were travel to an endemic area >7 days (adjusted OR [aOR]=4.3 [95%CI, 1.5-12]), age of 14-16 years (aOR=7.7 [95%CI, 1.6-38.3]) and mother's birth in an endemic area (aOR=5.2 [95%CI, 1.8-14.8]). CONCLUSION: Statistical evidence showed that travel to endemic areas and parents' place of birth both play a role in HAV serologic results in children with a significant difference of HAV seroprevalence between traveller and non-traveller children in France.

[Linezolide in paediatrics]. / Le linézolide en pédiatrie.

The spread of multiresistant Gram positive bacteria required the development of new drugs. Linezolid, a new oxazolidinone, is active against these pathogens and is marketed for the treatment of severe glycopeptides-resistant Gram positive-bacteria in adults. Moreover, the availability of intravenous and oral formulation with an excellent bioavailability of the latter, is hoped to facilitate the management of these infections. Most information regarding the pharmacoketic profile, efficacy and tolerability of linezolid in pediatric derived from adults studies. In this review we summarize evidence regarding the uses of linezolid in children focusing on the clinical efficacy data and safety in serious Gram-positive infections and also in compassional uses.

[Pneumococcal pneumonia highly probable in immunized children cared for in-group settings]. / Pneumonies à pneumocoque hautement probables chez les enfants vaccinés gardés en collectivité.

Invasive pneumococcal diseases were reduced after introduction of pneumococcal conjugate vaccine, but infections due to non-vaccine serotypes persisted. The pneumococcal origin of community-acquired pneumonia remains difficult to affirm, but high procalcitonin and C-reactive protein blood levels and duration of fever 48 h or less after initial antibiotic treatment are excellent predictors of pneumococci. Among 259 patients under 7 years of age hospitalized from 2003 to 2008 for community-acquired pneumonia, 47 met these criteria, including 27 of 141 hospitalized between 2006 (date of vaccine generalization) and 2008. Of these 27, 21 had previously received pneumococcal conjugate vaccine and 19 of 21 were attendees of nursery school or day care centers versus only 2 in 2003-2006. These data show that pneumococcal pneumonias are possible in immunized children cared for in-group settings.

[Should yellow fever vaccination be recommended during pregnancy or breastfeeding?]. / Vaccin amaril au cours de la grossesse ou de l'allaitement: que conseiller?

Yellow fever vaccine is produced from a live attenuated virus that is contraindicated in case of immunodeficiency and subject to restrictions for pregnant or breastfeeding women. The purpose of this review of available information on yellow fever vaccination during pregnancy and breastfeeding is to assist physicians in making recommendations prior to departure to yellow-fever endemic zones. Regarding pregnancy, there is no evidence to support a major risk of yellow-fever-vaccine-related complications in mothers or children. Although this finding is reassuring, it should be underlined that most reported series have been small. Regarding breastfeeding, the risk was recently confirmed by a report describing vaccine-induced encephalitis occurring in an infant 8 days after primary vaccination of the mother. The final decision to vaccinate depends on whether or not the trip can be postponed. If travel is mandatory, vaccination may be recommended in pregnant women preferably during the first trimester since the immunological response appears to be better at that time. Antibody titer should be checked following delivery. During breastfeeding, vaccination may be performed but breastfeeding must be stopped during the postvaccinal viremia phase. Breastfeeding can be resumed after a 10-day period of formula feeding.

[Imported malaria: diagnostic traps and rapid tests]. / Paludisme d'importation: pièges diagnostiques et tests de diagnostic rapide.

Imported malaria is a disease prevalent in France: 6,000 to 8,000 cases a year, of which 15% are pediatric cases. Despite this high incidence, the diagnosis is often delayed. The patient may then evolve to a severe form. This diagnostic delay is due to non-specific clinical symptoms in children. The most common symptoms are fever and digestive disorders (diarrhea, vomiting). In the absence of thrombocytopenia, the laboratory tests are not very useful for diagnosis. Parasitological examinations are dependent on the experience of the biologist, particularly in cases of low parasitemia as those observed in children who have received partial chemoprophylaxis. The recent introduction of rapid tests based on the detection of Plasmodium proteins, allows emergency remedy to this problem. The blood smears remains the gold standard and has to be used to confirm the results of rapid tests. If rapid tests improve the detection of Plasmodium in 2009, it remains mandatory to evoke the diagnosis of malaria in any febrile child coming from an endemic area.

Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells.

OBJECTIVES: The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses. METHODS: We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX). RESULTS: Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it. CONCLUSION: MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.