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Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide. Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H). Results: Of 17693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America). Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children., peer-reviewed

ObjectiveTo assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics.DesignParticipating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children.Results84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy.ConclusionsComprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.

Incorporation of thymidine into nuclear and mitochondrial DNA has been measured in the livers of normal rats and of rats killed 17 h or 24 h after partial hepatectomy. When total-body X-irradiation (500 or 1,500 R) is given at increasing intervals (up to 30 h) before sacrifice, a progressive decrease followed by a plateau of low level of incorporation is observed in the nuclear DNA (N-DNA) whereas the synthesis of mitochondrial DNA (M-DNA) first decreases until a minimal value is reached after 4 h in normal liver and 12 h in regenerating liver, then recovers at an exponential rate, quite independently of the nuclear DNA synthesis. The results suggest that irradiation can interfere with the enzymatic processes of both M-DNA and N-DNA syntheses, but that the persistence of the inhibition of N-DNA synthesis must be ascribed to a temporary block in the cell cycle. The SH-protector AET injected to non-irradiated rats exerts a very small inhibitory effect on normal liver N-DNA and M-DNA synthesis. In regenerating liver, both syntheses are affected rather similarly suggesting a common mechanism of inhibition through impairment of some step in the synthetic process.

Male rats were injected with hydroxyurea (100 mg/kg or 500 mg/kg) and sacrificed at different times after injection. [14C]-thymidine is injected 1 hr before sacrifice and the specific radioactivity determined in total DNA of spleen, thymus and regenerating liver and in nuclear and mitochondrial DNA of normal and regenerating liver. Total DNA synthesis is rapidly inhibited in lymphoid tissues and in regenerating liver, but recovery is more rapid in the latter organ. Inhibition of DNA synthesis occurs more slowly in the mitochondria than in the nuclei of normal and regenerating liver; the rate of recovery is also lower in the mitochondria. These differences between the two DNA are tentatively ascribed to a less rapid exhaustion of the intra-mitochondrial pool of deoxynucleotides as regards the inhibition phase, and to a competition for the precursor pool between N-DNA and M-DNA syntheses, in favor of the predominant one (N-DNA synthesis) as regards the recovery phase.

Epidermal growth factor receptors (EGF-R) have been measured in human tumors of the Central Nervous System (CNS) by 125I EGF ligand binding. High affinity receptors (Ka congruent to 1 x 10(9) M-1) were detected in nearly all individual specimens of meningiomas and tumors of glial origin (astrocytomas, glioblastomas). The phosphotyrosine kinase activity associated with the EGF-R was evaluated by measuring the incorporation of gamma 32P-ATP, after immunoprecipitation of the receptor with the monoclonal antibody EGFRI. A good relationship was observed between the EGF-binding capacity and the autophosphorylation of the receptor, indicating that in most cases functional molecules of EGF-R were expressed on the tumor membranes. In the group of meningiomas, no relationship could be established between the EGF-R level and the histopathology of the tumors. Astrocytomas exemplify a progression of malignancy, from benign (low grade astrocytomas) towards an increased malignant phenotype (glioblastomas). In this group, our observations indicate a positive relationship between the EGF-R level and phosphokinase activity and the degree of malignancy.