Fusobacterium invasive infections in children: a retrospective study in two French tertiary care centres.

The purpose of this investigation was to describe the clinical and biological characteristics and evolution of invasive Fusobacterium infections in children admitted to two French paediatric tertiary care centres. Children who were admitted from 1998 to 2009 to two tertiary care centres for invasive Fusobacterium infection were included in a retrospective study. Thirty-one children with a median age of 5.7 years (interquartile range, IQR [2.3; 9.3]) were included. Nine children had an underlying condition, most commonly sickle cell disease (n = 3) or immunodeficiency (n = 3). Two children had skin effraction prior to the infection. The major sites of infection were the head and neck (n = 14) and abdomen (n = 10). Three children suffered from atypical Lemierre's syndrome. More than half of the children had a bacterial co-infection (58 %). Six children were hospitalised in an intensive care unit, and 67 % of them had a chronic underlying disease. None of the children died. Six children with negative cultures had Fusobacterium identified through 16S RNA-PCR. Fusobacterium is responsible for severe infection in children. Microbiological diagnosis might be improved by the wider use of molecular detection.

A new highly discriminatory multiplex capillary-based MLVA assay as a tool for the epidemiological survey of Pseudomonas aeruginosa in cystic fibrosis patients.

Multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) has been shown to provide a high level of information for epidemiological investigations and the follow-up of Pseudomonas aeruginosa chronic infection. In the present study, an automatized MLVA assay has been developed for the analysis of 16 VNTRs in two multiplex polymerase chain reactions (PCRs), followed by capillary electrophoresis. The result in the form of a code is directly usable for clustering analyses. This MLVA-16(Orsay) scheme was applied to the genotyping of 83 isolates from eight cystic fibrosis patients, demonstrating that the same genotype persisted during eight years of chronic infection in the majority of cases. Comparison with pulsed-field gel electrophoresis (PFGE) analysis showed that both methods were congruent, MLVA providing, in some cases, additional informativity. The evolution of strains during long-term infection was revealed by the presence of VNTR variants.

Epidemiological investigation of Pseudomonas aeruginosa isolates including multidrug-resistant serogroup O12 isolates, by use of a rapid and simplified multiple-locus variable-number of tandem repeats analysis and whole genome sequencing.

BACKGROUND: Clustered cases of Pseudomonas aeruginosa infection in immunocompromised patients' wards require rapid characterization of a potential epidemic to guide investigations and identify the potential source of contamination. AIM: To design and evaluate a rapid and simple typing method for P. aeruginosa in comparison to whole genome sequencing (WGS). METHODS: A simplified polymerase chain reaction based on multiple-locus variable-number of tandem repeats analysis (MLVA) was designed and used to investigate cases of P. aeruginosa infection and colonization in a paediatric haematology department. The method was compared to WGS by using the Illumina method. FINDINGS: On the 17 isolates recovered from 15 children (eight from blood cultures, three from urinary tract infections, one from sputum and five stool isolates), MLVA distinguished 10 different profiles, and seven isolates from six children shared the same profile. Analysis by WGS revealed that these seven isolates belonged to sequence type ST111 and serotype O12, allowing at least three different genotypes to be distinguished among them. Five environmental strains had three MLVA profiles; one was shared with a clinical isolate but WGS excluded any relationship. CONCLUSION: The simplified and inexpensive MLVA method enabled the exclusion, in less than 5 h, of most of the unrelated isolates and thus to focus investigations on a small number of cases, whereas WGS, taking several days of work, drew definitive conclusions concerning the outbreak and the genetic relationships of the ST111 isolates circulating in the department. We conclude that sequential use of both methods is the optimal strategy to investigate clustered cases of P. aeruginosa infections.

Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France.

BACKGROUND: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. METHOD: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. RESULTS: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae. CONCLUSION: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections.

Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4, south-western France, June 2011.

Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south-western France, household transmission due to Escherichia coli O104:H4 was suspected for two cases who developed symptoms 9 and 10 days after onset of symptoms of the index case. The analysis of exposures and of the incubation period is in favour of a secondary transmission within the family. Recommendations should be reinforced to prevent person-to-person transmission within households.

Subtyping of emm1 group A Streptococci causing invasive infections in France.

By combining PCR amplification of toxin-encoding genes and sic gene sequencing, we distinguished 24 genotypes among 47 M/emm1 group A streptococci isolated from children and adults in France in 9 cases of infection comprising four clusters and 38 unrelated invasive infection cases used as controls.

[Monitoring serum vancomycin concentrations in the treatment of Staphylococcus infections in children]. / Surveillance des taux sériques de vancomycine dans le traitement des infections à staphylocoque en pédiatrie.

INTRODUCTION: Vancomycin is the cornerstone of therapy against methicillin-resistant Staphylococcus in both community- and hospital-acquired infections. Monitoring vancomycin concentration is essential to prevent over- or underdosing of pediatric patients. However, only initial trough vancomycin concentrations may be needed to optimize dosages. The optimal rate of the trough serum level to the minimal inhibitory concentration (MIC) should be equal to or greater than 8 in severe infections. OBJECTIVES: The aim of this study was to analyze the initial trough serum levels of vancomycin obtained from pediatric patients treated with vancomycin for suspected or confirmed Staphylococcus infections in combination with MIC determination. PATIENTS: We reviewed the medical records of 3759 children aged, more than 1 month, and 358 neonate patients during a period of 10 years in Robert-Debré Hospital, Paris. METHODS: Serum levels were determined using the polarization fluorescence method. MIC was determined using the E-test method. RESULTS AND CONCLUSION: Of the 3759 children studied, 55% had a through serum level less than 10mg/L and 24% had greater than 15 mg/L. Of the 358 neonates, 43% had a trough serum level less than 10mg/L and 31% greater than 15 mg/L. Among these children, 425 had documented Staphylococcus bacteremia with vancomycin MIC determination. Determining the trough level concentration in infected pediatric patients remains mandatory to optimize the vancomycin regimen. The rate of the trough serum level to MIC was less than 4 in 50% of the patients and more than 10 in 5% of the patients.

[Epidemiology of acute otitis media caused by Streptococcus pneumoniae: emergence of serotype 19A]. / Epidémiologie des otites moyennes aiguës à pneumocoque : émergence du sérotype 19A.

In this study, the authors report the distribution of serogroups/serotypes and their susceptibility profiles of Streptococcus pneumoniae causing recurrent and difficulties to treat acute otitis media (AOM) in children obtained at the ENT outpatient clinic of Robert Debré Hospital in Paris, between 2002-2008 after the implementation of the 7-valent pneumococcal conjugate vaccine. In this retrospective study, 126 S. pneumoniae isolates were obtained by tympanocentesis from 126 children with AOM during three different periods: 2002-2003 (period 1), 2004-2005 (period 2), and 2006-2008 (period 3). In period 1, the most common serotype was 19F. Between period 1 and period 3, the proportion of serotype 19F decreased from 39 to 13% (P=0.03). In contrast, the proportion of serotype 19A increased from 25 to 60% (P=0.03). So, they observed that vaccine-related serotype 19A became dominant among young children with AOM in 2006-2008. Overall, 15.1% of the isolates were penicillin susceptible, 73.8% intermediate and 11.1% were resistant. Most (94%) of the S. pneumoniae serotype 19A were penicillin intermediate.

Hemolytic uremic syndrome due to Shiga toxin-producing Escherichia coli infection.

The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment. The main symptom is diarrhea, which is bloody in about 60% of patients and occurs after a median incubation period of three days. Shiga toxins released by STEC induce a cascade of thrombogenic and inflammatory changes of microvascular endothelial cells. HUS is observed in 5-15% of STEC infection cases, defined by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal injury. The diagnosis of STEC infection relies on biological screening for Shiga toxins and STEC in stools and serology. Treatment of STEC-HUS is mainly symptomatic, as no specific drug has proved effective. The effect of antibiotics in STEC infection and STEC-HUS remains debated; however, some bacteriostatic antibiotics might have a beneficial effect. Proofs of evidence of a benefit from complement blockade therapy in STEC-HUS are also lacking. Clinical and bacteriological STEC-HUS surveillance needs to be continued. Ongoing prospective studies will document the role of bacteriostatic antibiotics in STEC infection and STEC-HUS, and of complement blockade therapy in STEC-HUS.

Phylogenetic groups and virulence factors of Escherichia coli strains causing pyelonephritis in children with and without urinary tract abnormalities.

Escherichia coli isolates causing acute pyelonephritis in 93 children (25% with urinary tract abnormalities) were tested for nine virulence factors (papC, papGII, papGIII, sfa/foc, hlyC, cnf1, iucC, fyuA and iroN) and their phylogenetic groups were determined. Isolates lacking papGII were more frequent among patients with urinary tract abnormalities (58% vs. 10%, p 0.0003), as were non-virulent phylogenetic group A isolates (25% vs. 5%, p 0.043). Pyelonephritis caused by less virulent E. coli strains was more frequent among patients with significant urinary tract abnormalities. Further studies are required to determine whether screening for E. coli virulence factors may help to identify children warranting anatomical investigations.

[Rotavirus infections in a paediatric hospital during 5 years]. / Gastroentérites à rotavirus dans un hôpital pédiatrique au cours de cinq années consécutives.

Rotavirus is the major cause of gastroenteritis in children and the main cause of hospital acquired-infection in paediatric unit. We report the epidemiology of gastroenteritis in our hospital during five consecutive years. Rotavirus was involved in 13% of the patients. Seasonal peaks were observed in January and 45.8% of the patients were less than 6 month old. The rotavirus infection was hospital-acquired in 1/3 of the cases. During the winter period, the incidence of rotavirus nosocomial infection was 4.4%.

[Pseudomonas aeruginosa: resistance to antibiotics]. / Pseudomonas aeruginosa: résistances aux antibiotiques.

Pseudomonas aeruginosa antibiotic resistance mechanisms are both innate and acquired, different according to the considered antibiotic; epidemiological follow-up of AB resistance for this pathogen is managed through ONERBA network (www.onerba.org); therapeutic approaches must limit resistant strains diffusion and resistant mutants emergence.

[Acute ethmoiditis in children, a series of 125 cases]. / Ethmoïdites aiguës extériorisées de l'enfant: à propos d'une série de 125 cas.

UNLABELLED: Acute ethmoiditis are bacterial infections of ethmoid sinuses, which may spread to the orbital or the endocranial spaces. It is essential to fit the antibiotherapy to the bacteria responsible for these infections. POPULATION AND METHODS: The charts of children hospitalized from 1995 to 2003 for an acute ethmoiditis were reviewed, particularly the results of bacterial exams and the antibiotics delivered. RESULTS: Over this 9-year period, 125 children (mean age 4.5 years) were hospitalized for acute ethmoiditis. Eighty were checked for blood cultures, which were sterile in 73 cases, and in the other cases, grew Staphylococcus, S. Pneumoniae or Streptococcus pyogenes. Seric soluble antigens were absent in the 5 cases where they were looked for. Ten children had a puncture of a subperiostal abscess: it was sterile in 5 cases, Staphylococcus was found in 4 cases, S. pneumoniae in the last case. Most children received an association of cefotaxim and fosfomycine for a mean duration of 5.6 days. Thirteen per cent of the children received 3 or 4 antibiotics. DISCUSSION: It is always difficult to found the bacteria responsible for an acute ethmoiditis. In our serie as in others, the most frequent bacteria were Staphylococcus, S. pneumoniae and S. pyogenes. CONCLUSION: In view of the bacteria responsible for these infections and their antibiotic resistance, we suggest the association of cefotaxim and fosfomycin for the first line of treatment of acute ethmoiditis.

[Two cases of Pseudomonas aeruginosa neonatal meningitis treated by ciprofloxacine]. / Infections néonatales a Pseudomonas aeruginosa et atteintes neuroméningées. Intérêt de la ciprofloxacine.

Two cases of Pseudomonas aeruginosa neonatal meningitis are reported. Case 1 occurred on day 6 of life, at home, in a full term newborn. Favourable outcome was obtained with a treatment associating ceftazidime, 21 days, gentamicin, 10 days and ciprofloxacin, 10 days. Case no 2 was a nosocomial meningitis in a 32 weeks and 4 days gestational age premature newborn. Despite in vitro effective antibiotherapy with ceftazidime, netilmicine and ciprofloxacine, six cerebral abscesses were observed during the second week of treatment. Ceftazidime was stopped after 6 weeks and ciprofloxacine prolonged until neuroradiological cure of cerebral lesions at one year of age. Normal outcome was observed at 3 and 4 and half year of age. Therapeutic indications and clinical tolerance of ciprofloxacine in neonatal meningitis are discussed.

[Optimal vancomycin serum level in Staphylococcus aureus infections?]. / Comment optimiser le taux sérique de vancomycine dans le traitement des infections à Staphylococcus aureus?

Vancomycin is the cornerstone of therapy against methicillin-resistant Staphylococus aureus in both community and nosocomial-acquired infections. Because vancomycin is a concentration-independent or time-dependant antibiotic, most clinicians have abandoned the routine practice of determining peak serum concentrations to rely solely on monitoring serum concentrations. The so-called therapeutic range most often quoted for vancomycin was assessed for through serum concentrations of 5-10 mg/l. But prolonged exposure to serum concentration close to the MIC is associated with the emergence of resistance. More recent guidelines recommended vancomycin in concentrations of 15-20 mg/l for the treatment of severe Staphylococcus infections or in situations where vancomycin penetration is poor. However, because of the great variability of vancomycin MIC(S) (0,12-4 mg/l) of susceptible Staphylococcus strains, guidelines should recommend through serum concentrations of 5-10 times the MIC.

Shiga toxin-producing Escherichia coli strains isolated from dairy products - Genetic diversity and virulence gene profiles.

Shiga toxin-producing Escherichia coli (STEC) are widely recognized as pathogens causing food borne disease. Here we evaluate the genetic diversity of 197 strains, mainly STEC, from serotypes O157:H7, O26:H11, O103:H2, O111:H8 and O145:28 and compared strains recovered in dairy products against strains from human, meat and environment cases. For this purpose, we characterized a set of reference-collection STEC isolates from dairy products by PFGE DNA fingerprinting and a subset of these by virulence-gene profiling. PFGE profiles of restricted STEC total DNA showed high genomic variability (0.9976 on Simpson's discriminatory index), enabling all dairy isolates to be differentiated. High-throughput real-time PCR screening of STEC virulence genes were applied on the O157:H7 and O26:H11 STEC isolates from dairy products and human cases. The virulence gene profiles of dairy and human STEC strains were similar. Nevertheless, frequency-wise, stx1 was more prevalent among dairy O26:H11 isolates than in human cases ones (87% vs. 44%) while stx2 was more prevalent among O26:H11 human isolates (23% vs. 81%). For O157:H7 isolates, stx1 (0% vs. 39%), nleF (40% vs 94%) and Z6065 (40% vs 100%) were more prevalent among human than dairy strains. Our data point to differences between human and dairy strains but these differences were not sufficient to associate PFGE and virulence gene profiles to a putative lower pathogenicity of dairy strains based on their lower incidence in disease. Further comparison of whole-genome expression and virulence gene profiles should be investigated in cheese and intestinal tract samples.

[Nosocomial rotavirus gastroenteritis]. / Gastro-entérites nosocomiales à rotavirus : étude rétrospective dans un service de pédiatrie générale.

Rotavirus is the most common cause of gastroenteritis in children requiring hospitalization. It is a very resistant and contagious virus causing nosocomial gastroenteritis. In France, the vaccine against rotavirus has been available since 2006, but the vaccine is not recommended for infant vaccination. The aim of this retrospective study was to describe nosocomial rotavirus gastroenteritis (NRGE) and to assess its impact on children hospitalized in the General Pediatrics Department of Robert-Debré Hospital (Paris) between 1 January 2009 and 31 December 2013. We analyzed the demographic characteristics of children (age, term birth, underlying diseases) and the severity of the NRGE (oral or intravenous hydration), and assessed whether these children could benefit from vaccination against rotavirus. RESULTS: One hundred thirty-six children presented nosocomial rotavirus infection, with an incidence of 2.5 NRGE per 1000 days of hospitalization. The incidence of NRGE was stable between 2009 and 2013 despite the introduction of specific hygiene measures. The average age of the children was 7 months (range: 0.5-111 months). Most often NRGE occurred in children hospitalized for respiratory diseases (65% of cases) and requiring prolonged hospitalization (median: 18 days). One-third of children were born premature (25%). Hydration was oral in 80 patients (59%), by intravenous infusion in 18 patients (13%), and intraosseous in one patient. Half of the patients were aged less than 5 months and could benefit from the protection afforded by vaccination. CONCLUSION: NRGE are common. Rotavirus mass vaccination should have a positive impact on the incidence of NRGE by reducing the number of children hospitalized for gastroenteritis, therefore indirectly reducing the number of hospital cross-infections of hospitalized children who are too young to be vaccinated.

[Ureaplasma urealyticum and Mycoplasma hominis infections in newborns: personal data and review of the literature]. / Ureaplasma urealyticum, Mycoplasma hominis et pathologies néonatales: Données personnelles et revue de la littérature.

Ureaplasma urealyticum and Mycoplasma hominis colonized 20-40% of newborns and are more frequent in premature. They are responsible for localized infections such as pleural effusion, pneumopathy, adenopathy, abscess or systemic sepsis. An important hyperleukocytosis is often associated with pulmonary infections. Their responsibility, as pathogen agents, is questionable in some non bacterial meningitis. There is large controversy for their role as cofactor, in chronic lung disease (bronchopulmonary dysplasia) and periventricular leukomalacia, because of a too low number of newborns in prospective trials. Genital mycoplamas are resistant to beta lactamines. Macrolides have a good sensitivity, particularly josamycine, but Mycoplasma hominis is resistant to erythromycin. For systemic sepsis, fluoroquinolones such as ciprofloxacine have less deleterious effects than IV erythromycin.