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OBJECTIVES: The objective of this study was to evaluate the ability of weighted-incidence syndromic combination antibiograms (WISCAs) to inform the selection of empirical antibiotic regimens for suspected paediatric bloodstream infections (BSIs) by comparing WISCAs derived using data from single hospitals and from a multicentre surveillance dataset. METHODS: WISCAs were developed by estimating the coverage of five empirical antibiotic regimens for childhood BSI using a Bayesian decision tree. The study used microbiological data on ∼2000 bloodstream isolates collected over 2 years from 19 European hospitals. We evaluated the ability of a WISCA to show differences in regimen coverage at two exemplar hospitals. For each, a WISCA was first calculated using only their local data; a second WISCA was calculated using pooled data from all 19 hospitals. RESULTS: The estimated coverage of the five regimens was 72%-86% for Hospital 1 and 79%-94% for Hospital 2, based on their own data. In both cases, the best regimens could not be definitively identified because the differences in coverage were not statistically significant. For Hospital 1, coverage estimates derived using pooled data gave sufficient precision to reveal clinically important differences among regimens, including high coverage provided by a narrow-spectrum antibiotic combination. For Hospital 2, the hospital and pooled data showed signs of heterogeneity and the use of pooled data was judged not to be appropriate. CONCLUSIONS: The Bayesian WISCA provides a useful approach to pooling information from different sources to guide empirical therapy and could increase confidence in the selection of narrow-spectrum regimens.

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.

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30–44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from “dose adjustment/closer monitoring”, in mild to moderate liver disease, to “the use is contraindicated” in severe liver disease.

The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares.