Aminoglycoside prescription: compliance with national guidelines in a pediatric hospital.

OBJECTIVE: Our study aimed to describe the use of aminoglycosides (AGs) in the pediatric population in acute settings and to assess its compliance with the most recent national recommendations. METHODS: A single-center retrospective study conducted over a 5-month period. Pediatric patients who received at least one dose of AGs in emergency or intensive care unit were included. Compliance with the 2011 French recommendations was assessed. RESULTS: A total of 153 AG prescriptions (120 with gentamicin and 33 with amikacin) for 139 patients (median age of patients = 10 months [IQR: 3-36]) were analyzed. Most of the AG prescriptions were initiated in the emergency department (n = 117, 76%) and, overall, compliance with national guidelines was met in half (n = 77) of the prescriptions. In the emergency department, cases of misuse concerned the indication, mostly for patients with pyelonephritis. In the pediatric intensive care unit setting, the misuse concerned underdosing and a low rate of pharmacological monitoring. CONCLUSION: AGs are still misused in pediatric acute settings. In order to limit drug resistance and to be more efficacious, higher doses should be used and monitoring should be performed, in particular in pediatric intensive care units. In the emergency department, more objective criteria should be used to initiate AGs.

Clinical, functional and genetic characterization of 16 patients suffering from chronic granulomatous disease variants - identification of 11 novel mutations in CYBB.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X-linked CGD (X91-CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910 , X91- or X91+ ), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910 -CGD and two X91- -CGD). One X910 -CGD was due to a new and extremely rare double missense mutation Thr208Arg-Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock-out PLB-985 cell line. Both mutations leading to X91- -CGD were also novel; one deletion, c.-67delT, was localized in the promoter region of CYBB; the second c.253-1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124-nucleotide pseudo-exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91- -CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three-dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91- -CGD patients correlates with mild clinical forms of CGD, whereas X910 -CGD and X91+ -CGD cases remain the most clinically severe forms.

Endogenous endophthalmitis as a severe complication following a Streptococcus pyogenes infection.

The diagnosis of endogenous endophthalmitis is challenging. We report a pediatric case of endogenous endophthalmitis due to Streptococcus pyogenes angina. A previously healthy 33-month-old child presented to the emergency department with a history of fever and fatigue related to bacterial angina. On physical examination, an opalescent cornea was noticed and the diagnosis of endogenous endophthalmitis was confirmed by the pediatric ophthalmologist. Streptococcus pyogenes was found in blood culture and in the anterior chamber fluid. There was an adverse outcome with posterior vitrectomy and eye atrophy. Since endogenous endophthalmitis can lead to a poor visual outcome, urgent therapeutic management is necessary.

Splenic infarction associated with transient anti-prothrombin antibodies is a rare manifestation of acute Mycoplasma pneumoniae infection.

We report the first paediatric case of splenic infarction following acute Mycoplasma pneumoniae infection with induction of anti-prothrombin (aPT) antibodies. A 12-year-old boy was admitted to the paediatric emergency department for a left pleuropneumonia and a splenic infarction. aPT antibodies were transitorily detected. The patient recovered fully after antibiotic therapy and a 3-month course of anticoagulation treatment. Antiphospholipid (aPL) antibodies induced by acute infections have already been reported but cases of clinically relevant thrombosis remain rare. The pathogenicity of aPT antibodies is discussed here. We hypothesize that these antibodies were involved in this symptomatic hypercoagulable state.

Neonatal fever: A puzzling case.

Toxoplasmosis is a potentially serious fetal infection associated with maternal seroconversion of toxoplasmosis during pregnancy. Follow-up and treatment vary between different countries. We present a case of congenital toxoplasmosis with unusual physiopathology and symptomatology. The mother was immunized before the beginning of pregnancy but immunosuppressive treatments for Crohn disease maintained during the pregnancy could explain toxoplasmosis reactivation in the mother and congenital toxoplasmosis. The baby presented reversible B lymphopenia and hypogammaglobulinemia.

[Acute epiglottitis due to Haemophilus influenzae b: A severe consequence of increased skepticism about vaccination]. / Épiglottite aiguë à Haemophilus influenzae b : conséquence grave du scepticisme vaccinal.

Acute epiglottis is a life-threatening disease in relation with the occurrence of an acute upper airway obstruction. Its incidence has fallen dramatically since the widespread introduction of Haemophilus influenzae type b (Hib) conjugate vaccine. We report the case of a 26-month-old child who was not fully immunized and presented acute upper airway respiratory distress with fever. The symptoms quickly evolved to a respiratory arrest condition with bradycardia, revealing epiglottitis due to Hib. Despite high immunization coverage with great efficacy and occurrence of herd immunity, this entity still exists because of the French population's skepticism of the routine vaccination schedule.

[Bacillus Calmette-Guérin osteomyelitis. A case report in a former preterm baby]. / Ostéomyélite secondaire à une vaccination par le bacille de Calmette et Guérin : à propos d'un cas chez un ancien prématuré.

Postvaccination osteo-articular mycobacterial infectious disease is a rare and potentially serious complication after Bacillus Calmette-Guérin (BCG) vaccine. We report on a case of a former preterm baby born at 30 weeks of gestation who was vaccinated with BCG Copenhagen strain at 2 months of age. He presented 6 months later with a painful limp, which was found to be a mono-articular osteitis of the right ankle. Histology of the biopsy showed signs of mycobacterial infection and molecular analysis confirmed a BCG infection. Blood tests did not reveal any immunodeficiency associated with the disease (IFN-gamma levels were normal). The course of the disease was favorable with 9 months of antibiotic therapy against mycobacteria. BCG complications should lead to screening for immunodeficiency. The prognosis of BCG osteitis is excellent if the disease is localized. No link between prematurity and BCG complications has been found to date. BCG vaccination of premature infant should be the same as for the general population.

[Extensive swelling reaction after a pentavalent vaccination]. / Réaction locale étendue à un vaccin pentavalent.

Injection site reactions (ISRs) are quite common side effects defined by a local adverse drug reaction directly caused by a vaccine. Twenty-four hours after an intramuscular injection (in the deltoid muscle) of the diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, Haemophilus influenza type b (DTPCa-Hib) combined vaccine, a 3-year-old boy developed fever. A few hours later, local redness and swelling appeared at the injection site, with rapid extension to the entire limb, it was pain-free, and no other clinical anomalies were present. The patient received intravenous antibiotics for suspected cellulitis. The progression was favorable in 12h (apyrexia and decreased limb swelling), allowing the intravenous antibiotic treatment to be discontinued. Since the child was in excellent general health and recovery was fast, an ISR was diagnosed. Extensive limb swelling is frequent, mostly after the fourth dose of DTPCa-Hib. Deltoid muscle injection of DTP vaccine increases the risk of ISR compared to injection in the thigh, before the age of 3 years. The introduction of acellular pertussis vaccine decreased the risk of general side effects but may increase the risk of ISR. These reactions disappear with symptomatic treatment and do not contraindicate the product.

Assessment of the IgA immunosorbent agglutination assay for the diagnosis of congenital toxoplasmosis on a series of 145 toxoplasmic seroconversions.

A retrospective analysis of 145 medical records from our teaching hospital laboratory showed an overall specificity of greater than 97% for the IgA immunosorbent agglutination assay (ISAGA A) performed on the sera of babies to diagnose congenital toxoplasmosis (CT). These actualized data emphasize the ability of this test to confirm a diagnosis of congenital toxoplasmosis.

[YEL-AND meningoencephalitis in a 4-year-old boy consecutive to a yellow-fever vaccine]. / Méningo-encéphalite après vaccination anti-amarile : syndrome de YEL-AND.

Yellow fever is a vector-borne disease transmitted by an endemic mosquito in sub-Saharan Africa and tropical South America. It causes fever and possibly liver and renal failure with hemorrhagic signs, which may be fatal. The yellow-fever vaccine is an attenuated vaccine that is recommended for all travelers over the age of 9 months in high-risk areas. Adverse effects have been reported: minor symptoms (such as viral syndrome), hypersensitivity reactions, and major symptoms such as viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND). The yellow-fever vaccine-associated autoimmune disease with central nervous system involvement (such as acute disseminated encephalomyelitis) associates fever and headaches, neurologic dysfunction, seizures, cerebrospinal fluid (CSF) pleocytosis, and elevated protein, with neuroimaging consistent with multifocal areas of demyelization. The presence of antibodies or virus in CSF, within 1-30 days following vaccination, and the exclusion of other causes is necessary for diagnosis. We describe herein the case of a 4-year-old child who presented with severe encephalitis consecutive to a yellow-fever vaccine, with favorable progression. Diagnosis is based on the chronology of clinical and paraclinical signs and the presence of yellow-fever-specific antibodies in CSF. The treatment consists of symptomatic treatment and immunoglobulin injection.

[A child with sepsis-associated encephalopathy]. / Encéphalopathie associée au sepsis (EAS), un cas pédiatrique.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction due to a systemic response to infection. We report the case of a 4-year-old girl with fever and vomiting for 48h, brought to the university hospital of Grenoble because of vigilance disorders, loss of verbal fluency, and a cerebellar syndrome. She had a biological infectious syndrome. Infectious encephalitis was suggested first, but the cerebral scan and the lumbar punction were normal. Magnetic resonance imaging (MRI) showed a diffuse brain edema with extended involvement of cortical and basal ganglia. The electroencephalogram was globally slow. The infectious syndrome was explained by perforated appendicitis with peritonitis, treated by surgery and antibiotic therapy. Other infectious explorations were negative. No metabolic or autoimmune diseases were found. Hence, our final diagnosis was sepsis-associated encephalopathy. After 1 year of follow-up care, her clinical exam, MRI, and EEG were normal. Sepsis-associated encephalopathy has been increasingly described in the adult population, but until today only three pediatric cases have been published. It is diagnosed when the patient has a severe infectious syndrome associated with neurologic symptoms, mostly vigilance or consciousness disorders, no signs of shock, and only when other potential reasons have been ruled out. The MRI shows non-specific diffuse lesions with vasogenic edema on the subcortical substance or on the basal ganglia and the thalami. The electroencephalogram is slowed down on the whole. The main differential diagnoses are infectious encephalitis, acute disseminated encephalomyelitis, and cerebral vasculitis. Posterior reversible encephalopathy syndrome is an MRI diagnosis that presents characteristics similar to SAE. In the future, it could be discovered that it is the same physiopathology. At the moment, we only treat the symptoms and the causative infection. Most of the time, patients have neurologic sequelae that affect their verbal fluency. It can persist from a few months up to 6yrs. Although quite slow, the neurologic progression is good. The mechanisms are studied and there are hopes for specific treatments. The main explanation seems to be immune with alterations of the blood-brain barrier. Cytokines and activated leukocytes may attack the cerebral substance.

[Unusual presentation of a severe Mycoplasma pneumoniae infection: report of 2 cases]. / Présentation inhabituelle d'une infection grave à Mycoplasma pneumoniae, à propos de 2 observations.

Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary symptoms are most common in children. We describe herein two unusual severe forms of M. pneumoniae infection without initial pulmonary symptoms. The first case is an 8-month-old boy who was hospitalized in the pediatric intensive care unit with severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical infection. Initial blood tests and x-ray did not aid the diagnosis. The blood tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared 24h later, and there was a pneumonia outbreak on the chest radiograph. The boy was given josamycin and improved quickly. The second case concerns an 8-year-old child who was hospitalized in the pediatric intensive care unit with toxic shock. No clinical infectious origin was found. A broad-spectrum antibiotic therapy was started with ceftriaxone and josamycin. The M. pneumoniae blood test came back positive, which confirmed the diagnosis of septic shock in M. pneumoniae, requiring adjustment of the antibiotic therapy. Current guidelines for the choice of probabilistic antibiotic therapy in case of severe sepsis do not include the case of M. pneumoniae. The early initiation of antibiotic therapy plays a major role in the prognosis of these patients. It seems useful to search for M. pneumoniae in cases of severe atypical infections, particularly in the absence of pulmonary symptoms.

[Mendelian susceptibility to mycobacterial disease: a case report of disseminated infection due to Mycobacterium avium]. / Syndrome de susceptibilité mendélienne aux infections mycobactériennes : à propos d'un cas d'infection disséminée à Mycobacterium avium.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic syndrome that predisposes patients to infections caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guérin (BCG) vaccines and nontuberculous environmental mycobacteria in children free of classical immunodeficiencies. This syndrome consists of impaired antimycobacterial immunity (axis IL12/INF-γ) constituting a new immune deficiency and outlining its major role in mycobacterial immunity. We report a new case of MSMD through the observation of a young girl with a disseminated infection due to Mycobacterium avium. The molecular defect was 2 autosomal recessive mutations of the IL12Rß1 gene (gene encoding for the ß1 chain of the IL12 receptor) leading to the absence of the IL12 receptor on the activated T lymphocytes' surface. IL-12RB1 deficiency is the most common genetic etiology of MSMD. Today, there are 6 MSMD-causing genes, leading to 13 distinct genetic disorders. The clinical phenotype differs between patients. The description of the molecular and immunological basis of this syndrome has allowed us to explain the pathophysiology of antimycobacterial immunity and is essential to understanding and managing these diseases.

[Sickle cell disease and invasive osteoarticular Salmonella infections]. / Drépanocytose et salmonelloses invasives ostéo-articulaires.

Non-typhi Salmonella are responsible for severe invasive infections in children with sickle cell disease, with osteoarticular locations that can affect short- and long-term outcomes. We describe the cases of 2 children with sickle cell disease who presented paucisymptomatic Salmonella osteoarticular infections on returning from North Africa. Progression was favorable in both cases after appropriate systemic antibiotic therapy, although one Salmonella was multidrug-resistant. Invasive salmonellosis remains rare in France, but, because of its severity, it should be suspected in any patient with sickle cell disease presenting fever, especially in the context of recent trips in Africa countries. Early clinical diagnosis is essential to start appropriate empirical treatment without waiting for bacteriological results.

Usefulness of Western blot in serological follow-up of newborns suspected of congenital toxoplasmosis.

The goal of the study reported here was to compare the results of Western blot with other serological methods for testing newborns suspected of having congenital toxoplasmosis. Western blot, enzyme-linked immunosorbent assay, immunoglobulin (Ig)M immunosorbent agglutination assay, and indirect immunofluorescence assay were performed on the sera of 126 neonates collected at birth and at 1 and 3 months of life. Western blot was more sensitive than IgM detection with the immunosorbent agglutination assay (82.6% vs. 69.6%), and the specificity of the two methods was 96.1% and 92.2%, respectively. Among the serological techniques tested, the combination of Western blot (IgG and IgM) with IgM immunosorbent agglutination assay achieved the greatest improvement in the sensitivity of early (postpartum) diagnosis of congenital toxoplasmosis.

[Congenital toxoplasmosis: prevention in the pregnant woman and management of the neonate]. / Toxoplasmose congénitale: prévention chez la femme enceinte et prise en charge du nouveau-né.

The management of a pregnant women or a child infected by Toxoplasma gondii rests on the screening of pregnant women at risk of infection. Treatment is prescribed if an infection occurs. A prenatal diagnosis (detection of T. gondii in amniotic fluid) may be performed, a positive result leading to a reinforcement of the treatment. After birth, the follow-up of the child is needed in order to prevent and detect the sequellae, mainly ocular. For all these steps, the biological methods used to diagnose T. gondii infection are of paramount importance.

[Acute Salmonella typhi meningitis in a 25-day-old newborn infant complicated by obstruction of the sylvian artery]. / Méningite aiguë à Salmonella typhi chez un nouveau-né de 25 jours compliquée de l'obstruction de l'artère sylvienne.

UNLABELLED: Acute Salmonella typhi meningitis is rare in neonates, mostly reported from developing countries with poor socioeconomic conditions. CASE REPORT: A male Caucasian newborn presented with acute Salmonella typhi meningitis at the age of 25 days. His parents had traveled across several African countries under rudimentary hygienic conditions a few months before his birth. Despite early and adapted antibiotic therapy (cefotaxime plus netilmycine), the child developed ischemia in the region of the left sylvian artery. CONCLUSION: Salmonella meningitis must be considered while dealing with a sick newborn whose mother has traveled across countries with endemic typhoid.

[The pediatrician and hepatitis C virus]. / Le pédiatre et le virus de l'hépatite C.

The recognition that hepatitis C virus can be transmitted perinatally or through blood transfusions warrants particular attention by the pediatrician. This paper highlights the epidemiology, diagnosis, natural history and management of hepatitis C in infants and children.

Monitoring rotavirus environmental contamination in a pediatric unit using polymerase chain reaction.

Rotavirus environmental contamination in a pediatric unit was investigated. Surfaces were swabbed, then viruses eluted, ultracentrifuged, and detected by polymerase chain reaction (PCR) amplification. Of 55 samples, 25 (46%) tested positive. Rotavirus RNA was more prevalent on surfaces in direct contact with children (thermometers and play mats) than on other environmental surfaces (washbasins, door handles, etc). PCR has proved useful for monitoring rotavirus environmental contamination.

Lack of value of specific IgA detection in the postnatal diagnosis of congenital toxoplasmosis.

To improve the performance of the postnatal diagnosis of congenital toxoplasmosis, we assessed the detection of IgA antibodies to Toxoplasma gondii by ELISA, compared with that of IgM by ELISA, ISAGA, and IFAT and neosynthesized antibodies using Western blot. From 1993 to 1996, IgA antibodies were detected using the Toxo IgA test (SFRI, Société Française de Recherches et d'Investissements, Bordeaux, France), in 195 serum and cord blood samples from 63 infants born to mothers who seroconverted during pregnancy. Eighteen infants had proven congenital toxoplasmosis (confirmed by the presence of IgG after 12 months of life) and 45 had no congenital toxoplasmosis (negativity of IgG after 6-12 months of life). The sensitivity of IgA detection by ELISA on serum and cord blood samples was 38.9 and 54.5% respectively, which is low when compared with the sensitivity of IgM detection by ISAGA (66.7% on serum samples, 90.9% on cord blood), ELISA (61.1% on sera, 81.8% on cord blood) and Western blot (83.3% on sera, 72.7% on cord blood). IgA antibodies were never detected by ELISA earlier than IgM or neosynthesized Ig (antibodies synthesized by infants). Thus, the detection of IgA antibodies by Toxo IgA is not useful in improving the diagnosis of congenital toxoplasmosis.