Pediatric osteoarticular infections caused by Streptococcus pneumoniae before and after the introduction of the heptavalent pneumococcal conjugate vaccine.

Streptococcus pneumoniae is an uncommon cause of osteoarticular infections (OAI) in children. The objective of this study was to investigate the clinical and laboratory characteristics of pneumococcal OAI before and after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). Data were retrospectively collected from children aged <16 years who were hospitalized for pneumococcal OAI between 1997 and 2007 in four Parisian teaching hospitals. Forty-three children were included (32 with arthritis and 11 with osteomyelitis) and the median age of these children was 12.5 months (range 3 months to 14 years). Serotypes were available for 19/43 strains (44 %) from 1997 onwards and for 12/13 strains (92 %) from 2005 onwards. Seven unvaccinated children were infected with vaccine serotypes and we observed only one vaccine failure. After the introduction of PCV7, we noted an increase in short-term complications and the emergence of serotype 19A, which was penicillin-intermediate in 86 % of cases. After PCV7 introduction, serotype 19A was the most frequent serotype implicated in pediatric pneumococcal OAI. The 13-valent pneumococcal conjugate vaccine introduced in France in June 2010 should cover the emerging serotype.

Impact of implementing French antibiotic guidelines for acute respiratory-tract infections in a paediatric emergency department, 2005-2009.

Acute respiratory tract infections (ARTIs) are the main reason for antibiotic prescription in children. In 2005, the French Drug Agency published guidelines to minimise inappropriate use of antibiotics for ARTI. The purpose of this study was to assess the impact of implementing these guidelines in a paediatric emergency department. We retrospectively analysed data collected prospectively in a French paediatric emergency department from November 2005 (date of guideline implementation) to October 2009. For each child diagnosed with ARTI, we collected age, diagnosis, and prescribed antibiotics. We computed antibiotic prescription rates in the study population. During the study period, 53,055 children were diagnosed with ARTI and 59% of the 22,198 antibiotic prescriptions given at discharge were related to ARTI. The proportion of ARTI patients given antibiotic prescriptions fell from 32.1% during the first year to 21% in year 4 (p<10(-4), Cochran-Armitage test). Amoxicillin-clavulanic acid and amoxicillin accounted for 50% and 34% of antibiotic prescriptions for ARTI, respectively. French antibiotic guidelines led to significant decreases in antibiotic prescription for ARTI in our paediatric emergency department.

Raman spectroscopic analysis of the clonal and horizontal spread of CTX-M-15-producing Klebsiella pneumoniae in a neonatal intensive care unit.

Nosocomial outbreaks of extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae are an increasing concern in neonatal intensive care units (NICUs). We describe an outbreak of ESBL-producing K. pneumoniae that lasted 5 months and affected 23 neonates in our NICU. Proton pump inhibitor and extended-spectrum cephalosporin exposure were significantly associated with the risk of ESBL-producing K. pneumoniae colonisation and/or infection. Thirty isolates recovered from clinical, screening and environmental samples in the NICU were studied by means of Raman spectroscopy, pulsed-field gel electrophoresis and repetitive extragenic palindromic polymerase chain reaction (rep-PCR). The Raman clustering was in good agreement with the results of the other two molecular methods. Fourteen isolates belonged to the Raman clone 1 and 16 to the Raman clone 3. Molecular analysis showed that all the strains expressed SHV-1 chromosomal resistance, plasmid-encoded TEM-1 and CTX-M-15 ß-lactamases. Incompatibility groups of plasmid content identified by PCR-based replicon typing indicated that resistance dissemination was due to the clonal spread of K. pneumoniae and horizontal CTX-M-15 gene transfer between the two clones.

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.

[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.

[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%.

[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.

Bacterial contamination of enteral nutrition in a paediatric hospital.

A prospective study was performed in a paediatric hospital to evaluate the incidence of bacterial contamination in enteral nutrition bags and to determine the critical points of process. During two separate one-month periods, all children receiving pump-assisted enteral nutrition were enrolled in the study. Samples for microbiological analysis were collected from enteral nutrition bags after administration in the first and second study period (sample T(2)). In the second study period, two additional samples were made at the end of the feed preparation process. One was refrigerated immediately (sample T(0)) and the other was sealed in a tube that followed the enteral nutrition solution until the end of its administration (sample T(1)). Bacterial contamination was detectable above 10(2)cfu/mL. Twenty-six out of 40 patients were included in the first study period and 14 out of 44 in the second study period. Contamination (>10(2)cfu/mL) occurred in nine of 26 samples (35%) and seven of 14 samples (50%) in the first and second study periods, respectively. Of these, five (20%) and three (21%) contained significant contamination (>/=10(4)cfu/mL). Bacteria of low pathogenicity were found in T(0) samples. Bacteria present in T(2) samples were pathogenic and multiple in 50% of cases. These results suggest that manipulation of the enteral nutrition bags at the bedside is critical for bacterial safety.

[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.

Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis.

OBJECTIVE: To compare the efficacy and safety of amoxicillin (50 mg/kg/day divided twice daily) for 6 days and penicillin V (45 mg/kg/day divided into three doses/day) for 10 days in children with group A streptococcal (GAS) tonsillopharyngitis. METHODS: In a prospective, comparative, open, randomized, multicenter trial, children were scheduled to return for visits 4 days (main end point) and 1 month after the completion of treatment for clinical and bacteriologic assessment. Total DNA restriction fragment length polymorphism was used to compare pre- and posttreatment GAS isolates. RESULTS: Between September, 1993, and February, 1995, 321 children (161 amoxicillin, 160 penicillin V) were enrolled, among whom 318 (160 amoxicillin, 158 penicillin V) were evaluable for safety, and 277 were evaluable for efficacy. Four days after the completion of treatment, pretreatment GAS were eradicated from 118 of the 141 children receiving amoxicillin (83.7%) and 116 of the 136 (85.3%) taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 9.9% (n = 11) of the children receiving amoxicillin and 5.7% (n = 6) of those treated with penicillin V, bacteriologic recurrences in 5 and 3 patients, respectively. Adverse events related to the study medications were reported in 4 patients in the amoxicillin group and 8 in the penicillin V group. Drug-related adverse events leading to treatment discontinuation occurred in 3 patients, all in the penicillin V group. Compliance, based on diary cards and the weight of study drugs returned, was significantly better in the amoxicillin group. CONCLUSIONS. The efficacy and safety of amoxicillin (50 mg/kg/day twice daily) for 6 days were not statistically different from those of penicillin (45 mg/kg/d three times a day) for 10 days in the treatment of GAS tonsillopharyngitis.

High prevalence of erythromycin resistance of Streptococcus pyogenes in Greek children.

BACKGROUND: Macrolide resistance among Streptococcus pyogenes strains is increasing in many European countries. Greece was not considered a country with high prevalence of macrolide-resistant S. pyogenes strains, and until now the genetic mechanism of resistance was unknown. METHODS: During the 25-month period from December, 1998, to December, 2000, pharyngeal cultures for S. pyogenes were performed on 743 Greek children with the clinical diagnosis of pharyngitis. The children were 1 to 16 years old (median age, 7 years) and were living in Central and Southern Greece. S. pyogenes isolates were tested for their susceptibility to erythromycin, clarithromycin, azithromycin, clindamycin, penicillin G, amoxicillin/clavulanate and cefprozil. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance by means of PCR. RESULTS: Of a total of 275 S. pyogenes isolates recovered, 105 (38%) were erythromycin-resistant (MIC > or = 1 microgram/ml) [corrected], with 54, 45 and 1% of them carrying mef(A), erm(A) [subclass erm(TR)] and erm(B) gene, respectively. The prevalence of erythromycin-resistant strains was 29 and 42% during the time periods December, 1998, to December, 1999, and January, 2000, to December, 2000, respectively. All erythromycin-resistant isolates were also resistant to clarithromycin and azithromycin. The isolates carrying the erm(A) gene were inducibly resistant to clindamycin. The 275 S. pyogenes isolates had ceprozil MICs < or = 0.032 microgram/ml. CONCLUSIONS: The current high (38%) prevalence of erythromycin-resistant S. pyogenes in Central and Southern Greece requires continuous surveillance and careful antibiotic policy.

In-vitro bactericidal activity of four oral antibiotics against pathogens responsible for acute otitis media in children.

This study was designed to test the in-vitro activity of four oral antibiotics against the four microorganisms most frequently isolated in acute otitis media: beta-lactamase-positive Haemophilus influenzae (N = 10), beta-lactamase-positive Moraxella catarrhalis (N = 10), penicillin-sensitive Streptococcus pneumoniae (N = 11) and methicillin-sensitive Staphylococcus aureus (N = 10), by the bactericidal curve method. Bactericidal kinetics were determined for concentrations of antibiotic equivalent to those found in the middle ear after treatment: amoxycillin-clavulanic acid (2.5 mg l-1/0.6 mg l-1 and 2.5 mg l-1/1.2 mg l-1), cefaclor (1 mg l-1), erythromycin (0.5 mg l-1) and erythromycin/sulfisoxazole (0.2/3 mg l-1). The inoculum was of 10(6) colony-forming units (cfu) ml-1. The bacterial counts were performed after 5 h and 24 h using a spiral inoculator system. The results showed that amoxycillin-clavulanic acid had rapid bactericidal activity (< 24 h) on the tested organisms at each of the doses used (reduction < or = 3 log10 cfu ml-1) which was not observed with the other antibiotics at either 5 or 24 h. Erythromycin alone or combined with sulfisoxazole had a bacteriostatic effect on Moraxella catarrhalis and Streptococcus pneumoniae but not on Haemophilus influenzae or Staphylococcus aureus. Cefaclor had no bactericidal action under these conditions.

Nosocomial infections and hospital mortality: a multicentre epidemiology study.

The aim of this study was to evaluate the number of deaths associated with nosocomial infections (NI) and the contribution of these NI to death. A multicentre descriptive study was conducted in 16 tertiary-care hospitals (14 222 beds) in Northern France. Medical records of consecutive patients who died at least 48 h after admission were reviewed for cause of death, NI and disease severity, before admission and before NI onset. The contribution of NI to death was assessed by agreement between two physicians according to a three-category scale of probability. Among the 1945 patients who died during the study, 26.6% had an NI. According to the agreed diagnosis, NI contributed to the deaths of 284 (14.6%) patients(certainly for 6.6% and possibly for 8%), thereby ranking NI as the fourth most frequent cause of death. Considering the deaths that had not been anticipated independently of NI two weeks before they occurred, NI definitely contributed to 2.8% of them. Lower respiratory tract, bloodstream and surgical wound infections were responsible for 39, 20 and 14%, respectively,of all NI in these patients. The impact of NI on in-hospital mortality seems to be lower than had previously been estimated in France based on US data from the 1970s and 1980s. To improve healthcare quality, further studies are needed to elucidate the processes that may contribute to fatal severe NI.

In situ management and molecular analysis of candidaemia related to a totally implantable vascular access in a cystic fibrosis patient.

We describe a case of candidaemia in a paediatric cystic fibrosis (CF) patient with a totally implantable vascular access (TIVA). Serial quantitative blood cultures during therapy with amphotericin B delivered via the catheter suggested that the patient was responding to therapy. The TIVA was finally removed because of persistent fever, but its culture remained sterile. Randomly amplified polymorphic DNA (RAPD) analysis of Candida albicans from various anatomical sites showed that the patient's sputum was the most likely source of TIVA contamination. Investigation of TIVA-related candidaemia by molecular analysis could guide rational antifungal chemoprophylaxis of TIVA-related candidaemia.

Treatment failure in otitis media: an analysis.

An epidemiological study was conducted in order to monitor the involvement of penicillin-resistant pneumococci (PRP) in treatment failure in acute otitis media (AOM), in an area of France where resistance to antibiotics is high. A total of 293 children presenting to 12 ear, nose and throat (ENT) specialists were included in the study. The mean age of the patients was 15.3 months and most of the children (58.7%) were attending day care centres. Bacteriological sampling demonstrated that in 146 cases (49.8%), no pathogen was present at the time of treatment failure. In the remaining patients Streptococcus pneumoniae was the most frequently recovered pathogen, being isolated from 81/147 (55.1%) of bacteriologically documented cases. Serotype 23F was the predominant strain, representing 53% of all S. pneumoniae isolates recovered. Resistance or reduced susceptibility to the prescribed antibiotic was seen in 70/81 (86.4%) of the S. pneumoniae isolates. In 32 out of 49 children administered a beta-lactam antibiotic, treatment failure involved PRP. Amoxycillin seemed to be the most active oral beta-lactam against these pathogens. The multiresistance of S. pneumoniae poses a serious therapeutic problem and should make myringotomy and bacteriological sampling obligatory in cases of antibiotic treatment failure.

[Pneumococcal meningitis resistant to penicillin and nosocomial transmission in pediatric hospitals confirmed by genomic analysis]. / Méningite à la pneumocoque résistant à la pénicilline et transmission nosocomiale en milieu hospitalier pédiatrique confirmée par analyse génomique.

BACKGROUND: Careful epidemiological studies and sophisticated diagnostic procedures are necessary to prove that bacterial infection is nosocomial in origin. DNA finger printing method can be useful with this aim in view. CASE REPORTS: A 11 month-old girl suffered from a febrile pneumonia. She developed acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae, serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She died 24 hours later. Five days after this death, a 5 month-old infant hospitalized in the next bed developed an acute pulmonary infection due to the same strain with the same bacterial characteristics; this patient was cured with cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA analysis showed an identical profile of both strains. CONCLUSION: This is the first case of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRSP) associated with nosocomial spread between two children in adjacent beds. This case suggests that it is necessary to isolate patients with PRSP infection during hospitalization.

[Oropharyngeal flora. Epidemiologic survey of prevalence]. / Flores oropharyngées. Enquête épidémiologique de prévalence.

OBJECTIVES: Epidemiological surveys which are not frequently carried out in medical practice should provide useful information for the choice of antibiotics to be prescribed in community-acquired infections particularly with the recent development of therapeutic difficulties due to resistant strains. We therefore analyzed the prevalent pharyngeal flora in a general patient population. METHODS: The study was conducted during a single 24-hour period in 1991 by 43 general practitioners and included 645 subjects consulting for benign affections. No patient selection was made. Two pharyngeal swabs were obtained from each subject and cultured in aerobic and anaerobic conditions. Internationally accepted methods for identifying bacteria in pharyngeal samples all performed by one well-equipped laboratory. Beta-lactamase activity was determined with the nitrocephine technique, both directly and after culture. RESULTS: Patient age varied from 16 to 45 years; most (68.5%) consulted for reasons other than ear-nose-throat affections. Only 41 patients (4.3%) consulted for sore throat and 65.4% had not received antibiotics for at least 6 months. Haemophilus influenzae was found in 59.6% of the patients, 20% of the strains were beta-lactamase producers as were 83.7% of the Moraxella catarrhalis strains identified. CONCLUSION: These factors are indicators of potential risk of therapeutic failure when using beta-lactams unstable to beta-lactamases for the treatment of pharyngeal infections.

[Bacterial concentration in the cerebrospinal fluid in childhood meningitis]. / Concentrations bactériennes dans le liquide céphalo-rachidien au cours des méningites de l'enfant.

OBJECTIVES: The aim of this study was to analyze the epidemiological evolution of causal germs in meningitis in children aged 1 day to 15 years and determine the relationship between pretreatment concentrations of bacteria in cerebral spinal fluid (CSF), patient age, bacterial species and bacteriological eradication. PATIENTS AND METHODS: A quantitative analysis of germs was performed in 212 children with bacterial meningitis (mean age 19.8 months). RESULTS: Bacterial counts ranged from 2.10(1) to 4.10(9) CFU/ml in CSF. Among the 212 patients, 52 (24.5%) had counts 10(7)/ml. Infants had significantly higher counts than the other age groups. Mean counts for Hoemophilus influenzoe serotype B were not different from those for Streptococcus pneumoniae but were significantly higher than for Neisseria meningitidis. Compared with initial germ counts, 98.5% of the CSF specimens were sterile at 24 and 48 hours and 100% at 72 hours. CONCLUSION: Germ counts were higher in infants.

[Current Streptococcus pyogenes sensitivity responsible for acute tonsillopharyngitis in France]. / Sensibilité actuelle en France de Streptococcus pyogenes responsable d'angine aiguë.

OBJECTIVE: Current guidelines recommend that only tonsillopharyngitis due to group A beta-haemolytic streptococcus (GABHS) diagnosed by rapid diagnostic test should be treated with antibiotics. Empirical antibiotic therapy must be based on epidemiological surveillance of resistance of GABHS to antibiotics. The aim of our study was to assess the activity of antimicrobial agents currently recommended for the treatment of GABHS tonsillopharyngitis. Method The activity of penicillin G, amoxicillin, cefaclor, cefpodoxime, cefuroxime, erythromycin, clarithromycin and clindamycin was determined against 93 consecutive GABHS isolates collected in 2002. MIC50 and MIC90 of antibiotics tested were determined by agar dilution method according to CA-SFM guidelines. Macrolide resistance genes (ermA, ermB, mef) were detected by PCR. Genetic diversity of erythromycin-resistant isolates was analysed by pulsotypic method after digestion by SmaI (Finger-printing II, Biorad). RESULTS: The activity of beta-lactam agents tested was similar and no resistant strain was detected (0%). Nevertheless, this study shows an increasing emergence of erythromycin-resistant GABHS strains reaching 14% in 2002 (vs. 6.2% in a previous study carried out in 1996-1999). CONCLUSION: The empirical antibiotic therapy of tonsillopharyngitis must consider, on the one hand, the high risk of GABHS eradication failure associated with in vitro resistance to erythromycin and clarithromycin, and on the other hand, the sustained susceptibility of GABHS to beta-lactam agents. These results reinforce the recommendations to use beta-lactam agents as first line treatment of GABHS tonsillopharyngitis.