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The emergence of bacterial resistance and the lack of new antibiotics in the pipeline represent a public health priority. Maximizing the quality of antibiotic prescriptions is therefore of major importance in terms of adequate preparation and administration modalities. Adequate preparation prevents the inactivation of antibiotics and is a prerequisite to maximizing their efficacy (taking into account the pharmacokinetic/pharmacodynamic relationship) and to minimizing their toxicity. Many antibiotic guidelines address the choice of drugs and treatment duration but none of them exclusively address preparation and administration modalities. These guidelines are based on the available literature and offer essential data for a proper antibiotic preparation and administration by physicians and nurses. They may lead to a better efficacy and to a reduced antibiotic resistance. Such guidelines also contribute to a proper use of drugs and improve the interaction between inpatient and outpatient care for a better overall management of patients. [ABSTRACT FROM AUTHOR]

Hospitalization of a child for open heart surgery is a major event in a family's life. Apprehension of the surgical procedure can have serious psychological consequences and cause high anxiety for the child and his parents. Many interventions have been tried to reduce this preoperative anxiety, but there is no evidence to date on the best way to prepare these families for surgery. A phenomenological-inspired qualitative study with a reference framework of Wright and Leahey's family intervention model (2013) was conducted to evaluate a preparation for open heart surgery using doll play. To this end, semi-structured systemic interviews were conducted with ten families who benefited from the preparation (Among these families, 5 children have already been hospitalized for open heart surgery, the 5 others were hospitalized for the first time). The study took place within the M3 department of Marie Lannelongue Hospital. The Results of the research show that the families' experiences differ significantly. For families whose child is not having their first surgery, an additional hospitalization represents a new challenge with new difficulties to overcome. For the others, this first hospitalization is like a leap into the unknown (Fig. 1). Families whose child is hospitalized for cardiac surgery have a significant need for information about the hospitalisation and the surgery, depending on their stories and their beliefs. Even though the root-cause of anxiety are not the same for all the families, the resulting consequences of fear and apprehension are shared by all of them. Activity through play must therefore adapt to these parameters in order to effectively prepare families for surgery. This study provides a better understanding of the experiences of these children and their parents. In addition, it suggests generalizable improvements to other interventions so that care services can subsequently improve or build their own surgical preparation programs. [ABSTRACT FROM AUTHOR]

Summary Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L cells promotes nutrient disposal via the incretin effect. However, the majority of L cells are localized to the distal gut, suggesting additional biological roles for GLP-1. Here, we demonstrate that GLP-1 receptor (GLP-1R) signaling controls mucosal expansion of the small bowel (SB) and colon. These actions did not require the epidermal growth factor (EGF) or intestinal epithelial insulin-like growth factor (IGF1) receptors but were absent in Glp1r −/− mice. Polyp number and size were increased in SB of exendin-4-treated Apc Min/+ mice, whereas polyp number was reduced in SB and colon of Glp1r −/− : Apc Min/+ mice. Exendin-4 increased fibroblast growth factor 7 (Fgf7) expression in colonic polyps of Apc Min/+ mice and failed to increase intestinal growth in mice lacking Fgf7 . Exogenous exendin-4 and Fgf7 regulated an overlapping set of genes important for intestinal growth. Thus, gain and loss of GLP-1R signaling regulates gut growth and intestinal tumorigenesis. [ABSTRACT FROM AUTHOR]

Background & Aims: Glucagon-like peptide-2 (GLP-2) is a gut hormone that increases gut growth, reduces mucosal cell death, and augments mesenteric blood flow and nutrient absorption. Exogenous GLP-2(1-33) also stimulates glucagon secretion and enhances gut barrier function with implications for susceptibility to systemic inflammation and subsequent metabolic dysregulation. We examined the importance of GLP-2 receptor (GLP-2R) signaling for glucose homeostasis in multiple models of metabolic stress, diabetes, and obesity. Methods: Body weight, islet function, glucose tolerance, and islet histology were studied in wild-type, high-fat fed, lean diabetic, Glp2r −/− and ob/ob:Glp2r −/− mice. Results: GLP-2 did not stimulate glucagon secretion from isolated pancreatic islets in vitro, and exogenous GLP-2 had no effect on the glucagon response to insulin-induced hypoglycemia in vivo. Glp2r −/− mice exhibit no change in glycemia, and plasma glucagon levels were similar in Glp2r −/− and Glp2r +/+ mice after hypoglycemia or after oral or intraperitoneal glucose challenge. Moreover, glucose homeostasis was comparable in Glp2r −/− and Glp2r +/+ mice fed a high-fat diet for 5 months or after induction of streptozotocin-induced diabetes. In contrast, loss of the GLP-2R leads to increased glucagon secretion and α-cell mass, impaired intraperitoneal glucose tolerance and hyperglycemia, reduced β-cell mass, and decreased islet proliferation in ob/ob:Glp2r −/− mice. Conclusions: Our results show that, although the GLP-2R is not critical for the stimulation or suppression of glucagon secretion or glucose homeostasis in normal or lean diabetic mice, elimination of GLP-2R signaling in obese mice impairs the normal islet adaptive response required to maintain glucose homeostasis. [Copyright &y& Elsevier]

Summary: Objectives: To evaluate whether in vitro response to Mycobacterium tuberculosis RD1 peptides selected by computational analysis, measured by IFN-γ, IP-10, MCP-2 or IL-2 production, is associated with active tuberculosis (TB) in a country with a high incidence of TB. Methods: 129 individuals were prospectively enrolled, 41 with active-pulmonary TB and 88 without (household contacts and community controls). A whole blood assay based on RD1 selected peptides was performed. Soluble factors were evaluated by ELISA in plasma harvested at day1-post-culture. Enrolled individuals were also tested by QuantiFERON TB-Gold In tube (QFT-IT) and tuberculin skin tests (TST). Results: IFN-γ response to RD1 selected peptides was significantly higher in active TB patients than in household contacts and community controls. IP-10 and MCP-2 response did not differ between active TB patients and household contacts, although it was higher in these groups compared to community controls; conversely IL-2 response did not differ among the three groups. When IFN-γ response to RD1 selected peptides was scored based on receiver-operator-characteristic analysis, active TB was predicted with 68% sensitivity and 86% specificity. QFT-IT and TST showed a sensitivity for active TB of 90% and 68% and a specificity of 58% and 59%, respectively. Conclusions: IFN-γ (but not IP-10, MCP-2 and IL-2) response to RD1 selected peptides is associated with active TB with a higher specificity than QFT-IT and TST. [ABSTRACT FROM AUTHOR]

Background & Aims: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) activate pathways involved in beta cell survival and proliferation in vitro; we compared the relative importance of exogenous and endogenous GIP receptor (GIPR) and GLP-1 receptor (GLP-1R) activation for beta cell cytoprotection in mice. Methods: The effects of incretin hormone receptor signaling on beta cell regeneration and survival were assessed in mice following administration of streptozotocin in the absence or presence of the GIPR agonist [D-Ala2]-GIP (D-GIP), the GLP-1R agonist exendin-4, or the dipeptidyl peptidase-4 inhibitor sitagliptin. Beta cell survival was assessed in Gipr −/− mice given streptozotocin and by gene expression profiling of RNA from islets isolated from Glp1r −/− and Gipr −/− mice. The antiapoptotic actions of sitagliptin were assessed in wild-type and dual incretin receptor knockout (DIRKO) mice. Results: Administration of exendin-4 for 7 or 60 days improved blood glucose and insulin levels, reduced islet cell apoptosis, and increased pancreatic insulin content and beta cell mass. In contrast, D-GIP was less effective at improving these parameters under identical experimental conditions. Furthermore, Gipr −/− mice did not exhibit increased sensitivity to streptozotocin-induced diabetes. Sitagliptin reduced hemoglobin A1c levels and increased plasma and pancreatic levels of insulin after streptozotocin administration to wild-type mice. Sitagliptin reduced the levels of activated caspase-3 in wild-type islets but not in beta cells from DIRKO mice. Conclusions: There are functionally important differences in the pharmacologic and physiologic roles of incretin receptors in beta cells. GLP-1R signaling exerts more robust control of beta cell survival, relative to GIPR activation or dipeptidylpeptidase-4 inhibition in mice in vivo. [Copyright &y& Elsevier]

Summary: Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr−/− mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr−/− mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr−/− mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARα−/− hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting. [Copyright &y& Elsevier]

Abstract: Various emerging diseases have been reported in recent years as epidemiologic monitoring improves. These infections can compromise the pregnancy, through adverse maternal outcomes, as well as the outcome for the child following transmission. We report a review of the literature concerning the most quoted emergent virus (H5N1, SARS Coronavirus, Chikungunya, West Nile virus), and relate the perinatal management. [Copyright &y& Elsevier]

Infection is the major complication of long-term central venous catheters. Up to 1990, infection was confirmed by culture of the tip of the catheter, and more recently, by culture of clots inside the reservoir, but these techniques required removing the catheter. New techniques like quantitative paired blood cultures or differential time of positivation of paired blood cultures have allowed confirming infection without removing the catheter. Removal of the catheter, associated to a systemic antibiotherapy remains the standard treatment especially when the patient’s status is severe or when the infection is due to Staphylococcus aureus or Candida. More recently, a treatment was developed, based on maintenance of the device by using an antibiotic lock technique associated or not to a systemic antibiotherapy. Studies evaluating the efficacy of this alternative showed a rate of cure without relapse reaching 82% in case of tunnelized catheters and an efficacy varying from 30% to 80% in case of totally implantable port infection. Fibrin clots inside the reservoir of the device are out of reach for antibiotics and this may explain the persistence of microorganisms and the higher rate of failure. [Copyright &y& Elsevier]

Highlights from the article: Corynebacterium riegelii is a newly described Corynebacterium species, and was originally associated with urinary tract infections [1]. We report a rare case of urosepsis caused by C. riegelii in a 67-year-old female patient with neurogenic bladder, identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass-spectrometry (MALDI-TOF MS). Little is known about C. riegelii virulence factors for uropathogenesis, but as for C. urealyticum and Proteus mirabilis, C. riegelii exhibits strong urease activity, leading to an alkalinization of the urine, promoting lithogenesis [8]. Vancomycin remains the reference therapy for the empirical antibiotic treatment of Corynebacterium spp. infections [9], which should then be replaced by a narrower-spectrum penicillin according to the susceptibility profile.

Background & Aims: Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-like peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production. Methods: Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36 −/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting. Results: Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [3H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36 −/− mice. Conclusions: GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes. [Copyright &y& Elsevier]

Determines the characteristics of Streptococcus bovis infective endocarditis (IE). Use of penicillin G and amoxicillin as the principal antimicrobials; Mortality rate of IE; Prognostic factor of the disorder; Cardiac conditions associated with IE.

We reviewed 80 adult cases of measles seen in a Parisian hospital during the French 2010-2011 outbreak. Fifty per cent had at least one complication: pneumonia and hepatitis were the most frequent. Forty per cent of hospitalized cases did not have any complications, suggesting clinically poor tolerance of measles in adults. The outcome was always favourable. Subjects were younger, were more often French nationals and had a higher socio-economic status than the overall population. This report suggests that immunity resulting from natural disease in patients from an area where the disease is endemic is protective in the long term. [ABSTRACT FROM AUTHOR]

Objective The emergence of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has resulted in the increase of carbapenem prescriptions. The objective of our study was to determine the appropriateness of carbapenem prescriptions from initiation to reassessment of treatment, between 2009 and 2011. Patients and method A questionnaire drafted by infectious diseases specialists (IDS) and microbiologists was used to collect clinical and microbiological data concerning carbapenem prescriptions in 2009 and 2011. An IDS then compared the results to assess carbapenem prescription compliance with our hospital's local recommendations. Results Seventy-one prescriptions were included in 2009 and 32 in 2011. The carbapenem treatment had been most frequently probabilistic to treat nosocomial infections. The microbiological data revealed that the number of multidrug-resistant (MDR) infections had increased between 2009 and 2011, especially infections involving ESBL-producing Enterobacteriaceae . At treatment reassessment, in 2009 and 2011, 15 (21%) and 12 (38%) carbapenem prescriptions were appropriate and continued. Overall, when comparing the 2 periods, prescriptions complied with local guidelines from initiation to reassessment of treatment without any statistically significant difference (68% in 2009 and 75% in 2011). Conclusion Our study results showed that MDR infections had increased and especially infections due to ESBL-producing Enterobacteriaceae ; this was consistent with epidemiological data. We also proved that most carbapenem prescriptions were compliant with recommendations. The increased mobile IDS interventions in medical and surgical departments helped reach this rate of compliance. Carbapenem stewardship may be promoted even in a difficult epidemiological context, especially with IDS interventions for the duration of treatment or at treatment reassessment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We retrospectively studied daptomycin use during 2010 at the Bichat-Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin prescriptions. Patients and methods: Twenty-one patients were included and several parameters were documented: site of infection, bacterial species involved, reason for daptomycin use, dose and clinical outcome. Results: Ninety-five percent of daptomycin prescritions were off-label and most did not comply with local guidelines. Fifteen of the 21 patients were cured (71%), including 9 patients of the 12 with off-label and off-local recommendation prescriptions (75%). Osteitis and Enterococcus spp endocarditis were the new indications. Daptomycin was increasingly used at higher doses: 52% of our patients were given doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen responsible for infection is our patients, followed by Enterococcus spp. Conclusion: Daptomycin use is likely to evolve because of its effectiveness in the treatment of osteitis, left-sided and Enterococcus spp. infective endocarditis. It is generally used at higher doses, which are well tolerated. However, therapeutic monitoring needs to be developed. The antibiotic commission of our hospital gave new recommendations for daptomycin use in 2011. [Copyright &y& Elsevier]

Efavirenz has now become commonly used to treat HIV infection. Neuropsychiatric disorders have been reported in patients treated with efavirenz. Several factors often make it hard to determine the cause of these disorders: HIV infected patients take many different drugs, they may suffer from various organ diseases, and may also be heavily affected by problems in their everyday life. The French experts group working on neuropsychiatric side effects of efavirenz has undertaken a review of these disorders with the aim to identify: (1) semiology, (2) epidemiology in the global population, in HIV infected patients, and in patients treated with efavirenz. The expert group suggests recommendations to manage these disorders. [Copyright &y& Elsevier]

Clinical cases – We report three cases of acute renal failure during penicillin therapy for an infective endocarditis IE. The late occurrence, the decrease of creatinemia to normal after withdrawal of the drug, the presence of eosinophilia and, in one case, of eosinophiluria as well as the absence of any other cause of renal failure made the diagnosis of penicillin-induced allergic acute interstitial nephritis highly probable. This disease was first described in patients under methicillin treatment but may be observed with other beta-lactams. Only one third of patients present with the typical triad of renal failure with normal diuresis, fever, and rash. Acute interstitial nephritis should be considered as a potential cause of renal failure occurring during the treatment of infective endocarditis. [Copyright &y& Elsevier]

Introduction – objectifs Comparer les résultats des techniques d’Assistance Médicale à la Procréation (AMP) de femmes infectées par VIH-1 et de témoins séronégatives Matériels et méthodes Une étude rétrospective cas – témoins a analysé sur 3 ans (2009-2011) l’issue des techniques d’AMP chez les femmes infectées par VIH-1 suivies dans notre centre d’AMP, ayant les critères nationaux de prise en charge de stabilité de la maladie et d’accès légal à l’AMP. Les principaux items analysés ont été les taux de fécondation, d’implantation, de grossesse clinique et de naissance vivante. L’appariement a été effectué sur la date de la tentative, l’âge, la parité, la principale cause d’infertilité, la technique d’AMP et le rang de la tentative. Résultats 82 femmes infectées par VIH-1 et 82 témoins ont été incluses. Le nombre d’ovocytes et d’embryons obtenus, d’embryons transférés, et le taux de fécondation n’étaient pas différents. Le taux de grossesse clinique par transfert était significativement plus faible chez les femmes vivant avec VIH-1 que chez les témoins (15,9 % vs 36,3 %, p < 0,05), ainsi que le taux d’implantation (10,6 % vs 23 %, p < 0,02) et celui de naissance vivante (7 % vs 22,1 %, p < 0,02) Conclusion Les résultats de cette étude cas témoins, avec appariement sur 5 facteurs connus pour influencer les résultats de l’AMP, suggèrent que les femmes infectées par VIH-1, comme les spécialistes qui les suivent, doivent être informées des taux de réussite plus faibles dans les procédures d’AMP que ceux de la population générale, et par conséquent de ne pas différer, en cas de désir de grossesse, la démarche d’AMP, lorsque l’infection est stable, dans les situations d’échecs d’auto-insémination ou de toute autre cause d’infertilité. [ABSTRACT FROM AUTHOR]

Abstract: Systemic lupus erythematosus (SLE) remains of unknown origin. Herpes viridae infections seem to play a role in the pathogenesis of this disease. We report a 31-year-old man who presented an acute cytomegalovirus (CMV) infection with persistent fever and myopericarditis as the presenting manifestation of SLE. This case report emphasizes a difficult differential diagnosis between SLE and an acute CMV infection and suggests a possible role of this virus in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The characteristics of patients with a suspected SARS hospitalized in a Paris hospital were studied to analyze the hypothetic differences between epidemiologic and clinical teams in the management of an epidemic emerging disease, and to gather experience for the management of the next outbreak. Study design: All 90 patients hospitalized between March 16 and April 30, 2003, were included. Epidemiological and clinical data were shared with the French National Institute for Health. Cases were classified according to both the official definition (“possible”, “probable”, “excluded”) and a local one, adapted from the official definition but including an additional level of suspicion (“equivocal”), intermediate between “possible” and “excluded”. Results: The initial assessment was different in 39% of the cases (n=35), according to epidemiological (n=24) or clinical (n=11) elements. The final assessment diverged in 54% of the cases (n=47). All patients were officially considered as "excluded" for epidemiologists, while 47 remained as "possible" or "equivocal" cases of SARS according to the clinicians. Conclusion: The risk assessment was different in almost 40% of the cases, with no impact on epidemic diffusion or hospital-borne exposure as no probable case of SARS was diagnosed among these patients or their households. The confrontation of these different but complementary points of view will thus enrich the interdisciplinary management of eventual future outbreaks. [Copyright &y& Elsevier]