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.

Background: Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. Main text: Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. Conclusions: Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.

Animal experiments are widely used in preclinical medical research with the goal of disease modeling and exploration of novel therapeutic approaches. In the context of sepsis and septic shock, the translation into clinical practice has been disappointing. Classical animal models of septic shock usually involve one-sex-one-age animal models, mostly in mice or rats, contrasting with the heterogeneous population of septic shock patients. Many other factors limit the reliability of preclinical models and may contribute to preclinical research failure in critical care, including the host specificity of several pathogens, the fact that laboratory animals are raised in pathogen-free facilities and that organ support techniques are either absent or minimal. Advanced animal models have been developed with the aim of improving the clinical translatability of experimental findings. So-called animal ICUs refer to the preclinical investigation of adult or even aged animals of either sex, using—in case of rats and mice—miniaturized equipment allowing for reproducing an ICU environment at a small animal scale and integrating chronic comorbidities to more closely reflect the clinical conditions studied. Strength and limitations of preclinical animal models designed to decipher the mechanisms involved in septic cardiomyopathy are discussed. This article reviews the current status and the challenges of setting up an animal ICU.

A simple and rapid ultra-high-performance liquid chromatography (UHPLC) method using UV detection was developed for the simultaneous determination of eight β-lactam antibiotics in human plasma, including four penicillins, amoxicillin (AMX), cloxacillin (CLX), oxacillin (OXA), and piperacillin (PIP), and four cephalosporins, cefazolin (CFZ), cefepime (FEP), cefotaxime (CTX), and ceftazidime (CAZ). One hundred-microliter samples were spiked with thiopental as an internal standard, and proteins were precipitated by acetonitrile containing 0.1% formic acid. Separation was achieved on a pentafluorophenyl (PFP) column with a mobile phase composed of phosphoric acid (10 mM) and acetonitrile in gradient elution mode at a flow rate of 500 μl/min. Detection was performed at 230 nm for AMX, CLX, OXA, and PIP and 260 nm for CFZ, FEP, CTX, and CAZ. The total analysis time did not exceed 13 min. The method was found to be linear at concentrations ranging from 2 to 100 mg/liter for each compound, and all validation parameters fulfilled international requirements. Between- and within-run accuracy errors ranged from −5.2% to 11.4%, and precision was lower than 14.2%. This simple method requires small-volume samples and can easily be implemented in most clinical laboratories to promote the therapeutic drug monitoring of β-lactam antibiotics. The simultaneous determination of several antibiotics considerably reduces the time to results for clinicians, which may improve treatment efficiency, especially in critically ill patients.

Context: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR). Objective: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome Methods: We performed a retrospective cohort study including all lithium-poisoned patients admitted to the ICU in a university hospital. The usual clinical, biological and toxicological variables were collected. Poisoning severity was defined by seizures, catecholamine infusion, mechanical ventilation >48 h and/or fatality. Univariate followed by multiple logistic regression analyses were performed to identify prognosticators of poisoning severity and ECTR use. Results: From 1992 to 2013, 128 lithium-poisoned patients including acutely (10%), acute-on-chronically (63%) and chronically poisoned patients (27%) were included. The presumed ingested dose of lithium was 17.0 g [8.0–24.5] (median [25th–75th percentiles]). Serum lithium concentrations were 2.6 mmol/l [1.5–4.6], 2.8 mmol/l [1.8–4.5] and 2.8 mmol/l [2.1–3.0] on admission, peaking at 3.6 mmol/l [2.6; 6.2], 4.3 mmol/l [2.4; 6.2] and 2.8 mmol/l [2.1; 3.1] in the three groups, respectively. Severe poisoning occurred in 48 patients (38%) including four fatalities. Using the regression analysis, predictive factors of poisoning severity were Glasgow coma score ≤10 (Odds ratio (OR), 11.1; 95% confidence interval (CI), [4.1–33.3], p < 0.0001) and lithium concentration ≥5.2 mmol/l (OR, 6.0; CI, [1.7–25.5], p = 0.005). Ninety-eight patients (77%) developed acute kidney injury according to KDIGO criteria and 22 (17%) were treated with ECTR. Peak lithium concentration ≥5.2 mmol/l (OR, 22.4; CI, [6.4–96.4]; p < 0.0001) and peak creatinine concentration ≥200 μmol/l (OR, 5.0; CI, [1.4–19.2]; p = 0.01) were associated with ECTR use. Only 21/46 patients who presented one of these two criteria were actually treated with ECTR. More significant neurological impairment persisted on discharge in patients not treated with ECTR (p = 0.0007) despite not significantly shorter length of ICU stay. Conclusions: Lithium poisoning is responsible for severe impairments but rare fatalities. Severity can be predicted on admission using Glasgow coma score and lithium concentration. Our results suggest that ECTR could be indicated if serum lithium ≥5.2 mmol/l or creatinine ≥200 μmol/l.