Real-time PCR quantitation of hepatitis B virus total DNA and covalently closed circular DNA in peripheral blood mononuclear cells from hepatitis B virus-infected patients

International audienceIt remains unclear whether hepatitis B virus (HBV) replicates in extrahepatic tissues, and particularly in peripheral blood mononuclear cells (PBMCs), which may serve as a reservoir for the maintenance of infection. A real-time PCR assay for the quantitation of total and covalently closed circular (ccc) HBV DNA in serum and in PBMCs was developed. This assay was highly sensitive (detection limit: 27 IU/mL), linear over a wide range (9 log10), and was displayed high inter- and intra-assay reproducibility for the quantitation of total DNA. Genotypes A to E were detected and the results were consistent with those obtained with the COBAS Amplicor HBV Monitor Test. The specificity of the methodology was increased by prior treatment with an enzyme that digests relaxed circular DNA, and the elimination of background signals from virus adsorbed to the surface of PBMCs. HBV DNA was detected in the serum and PBMCs of 12 HBsAg-positive patients, with less than 1% in the cccDNA form. In conclusion, the quantitation of total and ccc HBV DNA in PBMCs is potentially useful as a non-invasive marker, and may help to increase our knowledge of the natural history of hepatitis B

A disseminated Mycobacterium marinum infection in a renal transplant HIV-infected patient successfully treated with a bedaquiline-containing antimycobacterial treatment: a case report

Background: Mycobacterium marinum disseminated infections rarely affected immunocompromised patients. Treatment with prolonged multi-drug regimen, exposed them to frequent drug-drug interactions and side effects.Case report: We reported a new case of Mycobacterium marinum disseminated infection in a 54-year-old renal transplant HIV-infected woman. Manifestations of the infection were cutaneous and sub-cutaneous nodules, mediastinal lymphnodes and left pulmonary infiltrate. Empirical treatment for nontuberculous Mycobacteria was first initiated with rifabutin, ethambutol, and azithromycin. After identification of M. marinum in sputum, regarding unfavourable clinical evolution and severe adverse events, treatment was changed for doxycyclin and rifabutin. Digestive and hematologic side effects motivated a new change of antimycobacterial treatment for a combination of moxifloxacin and bedaquiline. Tolerance was satisfactory. A twelve months treatment led to cure.Conclusion: We report the first case of M. marinum infection successfully treated with a bedaquiline-containing regimen. Bedaquiline could constitute an alternative to recommended antimicrobial regimens in case of nontuberculous mycobacterial disease including M. marinum infection

Recommandations sur les alimentations standard et thérapeutiques chez l’adulte en établissements de santé

International audienceObjectifsL’alimentation à l’hôpital est soumise à de multiples contraintes de fabrication, organisationnelle, sanitaire, écologique, qui influent sur le plateau repas proposé au patient. L’addition d’un ou plusieurs régimes peut ajouter à la complexité et contribuer à sa non-consommation et augmente les risques de dénutrition. L’élaboration de recommandations sur l’alimentation et les régimes à l’hôpital est d’un enjeu majeur.MéthodesUn groupe de pilotage constitué à parité par des médecins et diététiciens de l’Association Française des Diététiciens Nutritionnistes (AFDN) et de la Société Francophone de Nutrition Clinique et Métabolisme (SFNCM) a été constitué pour élaborer des propositions de recommandations, basées sur les résultats d’une enquête nationale sur les régimes à l’hôpital et sur les données de la littérature. Vingt-trois propositions de recommandations ont alors été soumises à 50 experts nationaux, selon la méthode DELPHI définie par la Haute Autorité de Santé d’élaboration de consensus formalisé d’experts.RésultatsCes vingt-trois recommandations ont été jugées appropriées et validées par un accord fort après trois tours de vote, après modifications et argumentations. Elles visent à définir chez l’adulte : 1-le vocabulaire lié aux alimentations/régimes à l’hôpital, 2-l’offre alimentaire (quantitative et qualitative), 3-la prescription nutritionnelle, 4-les modes alimentaires et adaptations aux patients, 5-délimiter les alimentations restreintes afin de réduire les régimes inutiles et sans preuve scientifique, 6-montrer l’importance de la place d’une alimentation spécifiquement adaptée aux patients dénutris et à risque de dénutrition.ConclusionCes recommandations devraient permettre à toutes les équipes de restauration et de soin, de rationnaliser l’offre alimentaire et les prescriptions d’alimentations thérapeutiques et de focaliser leur objectif sur la qualité d’une offre alimentaire adaptée aux besoins et au plaisir du patient

Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study

International audiencePurpose: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival.Methods: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression.Results: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality.Conclusion: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality

Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

International audienceBackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms.MethodsPlasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups.ResultsPublished models adequately described our data and could be used to predict Ctrough and AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine and ritonavir parameters was found between the two arms. However, darunavir Ctrough and AUC were significantly lower in the pentatherapy arm than in the tritherapy arm (P = 0.03 and P = 0.04, respectively).ConclusionsAdding maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir concentrations. Compliance issues, maraviroc–darunavir interaction and raltegravir–darunavir interaction were suspected and may affect the kinetics of viral decay during pentatherapy. A specific pharmacokinetic interaction study is needed to explore the interactions between darunavir and maraviroc and raltegravir

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence