Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors. MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597. We enrolled 818 cases from 372 centres, including 107 maternal-neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41-0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01-8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32-14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79-6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82-7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60-8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50-13·98], p=0·008). The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis. Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

The primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW. The research is a two-year observational cohort study (2017–2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse. The study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (p<0.0001). In addition, 69.2% of the 351 different combinations of an medication INN and a route of administration have no indication for the first month of life according to the French SmPC. Ninety-five percent of premature infants with GA less than 32 weeks received at least one medication not cited in SmPC. Neonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

Background: Pathogenesis of coagulase-negative staphylococcal bloodstream infections among preterm neonates is debated: central venous catheters (CVCs) are considered the major cause and the cornerstone of prevention measures. The role of other means of transmission is unknown. Methods: We developed a specific quantitative polymerase chain reaction assay targeting the dnaJ gene from Staphylococcus epidermidis and Staphylococcuscapitis to detect DNA from CVC used in preterms. Performance of the polymerase chain reaction was tested against 2 control groups of CVC yielding positive (n = 24) or negative (n = 63) conventional cultures. We also explored retrospectively the DNA load of CVC having a negative conventional bacterial culture and obtained from 34 very preterm neonates with catheter-related bloodstream infections (CR-BSIs) established by usual clinical and biologic criteria. Results: The molecular approach allowed detection of corresponding DNA from all the positive control catheters. Among the 34 episodes of CR-BSI yielding a negative conventional CVC culture, 8 (23.5%) had a positive polymerase chain reaction signal (5 S. epidermidis and 3 S. capitis). This percentage did not significantly differ according to the staphylococcal species, the delay between the CVC insertion and the beginning of the sepsis or between the blood culture collection and the CVC removal. These results conform to the previously published 70% of CR-BSI for whom the origin could be questioned. Conclusions: CVC removal in preterms is often performed in cases of CR-BSI; our study supports the hypothesis that in some cases the responsibility of CVC is questionable.

The amount of faecal pancreatic enzyme elastase 1 was significantly lower in 42 preterm newborns than in 12 full term babies at day 2 (89 (3–539) v 354 (52–600) μg/g, p<0.0007) and day 5 (164 (3–600) v 600 (158–600) μg/g, p<0.05) and correlated positively with total nutrient intake during the first week of life in preterm infants. This should probably be taken into account during early feeding.