Légionellose et infection par le virus d'immunodéficience humaine

La légionellose est une maladie grave et encore trop souvent sous-estimée, en particulier chez les patients immunodéprimés. Rarement décrite chez le patient infecté par le virus de l'immunodéficience humaine avant l'ère des traitements antirétroviraux efficaces, elle survenait chez les patients les plus immunodéprimés. Responsable de formes compliquées de pneumopathies, son pronostic était des plus réservés. Cette étude rétrospective descriptive a comparé les caractéristiques cliniques et évolutives de la légionellose entre deux cohortes de patients infectés ou non par le VIH, hospitalisé à l'hôpital Henri Mondor entre 1998 et 2004. La cohorte VIH- comportait 36 patients, dont 60% étaient immunodéprimés. La cohorte VIH+ se composait de 6 patients sous traitement antirétroviral efficace, peu immunodéprimés (taux moyen de lymphocytes T CD4+ = 479 +- 144/mm3). Aucun n'était sous chimioprophylaxie des maladies opportunistes. Chez les patients VIH+, le diagnostic a été constamment posé par l'antigénurie légionelle. La présentation clinique et l'évolution de la cohorte VIH+ étaient comparables à celles des patients VIH- .Le pronostic de l'affection chez les patients VIH+ était meilleur que celui des patients VIH- immunodéprimés, chez lesquels ont été constatées les formes les plus graves, voire mortelles. Malgré une diminution de la prophylaxie par cotrimoxazole au sein de la cohorte des patients infectés par le VIH, il n'a été observé d'augmentation de la légionellose chez ces patients, ce qui suggère que la restauration immunitaire par les traitements antirétroviraux confère une immunité au moins partielle contre cette maladie. La légionellose doit néanmoins être recherché devant toute pneumopathie bactérienne chez un patient VIH+, quel que soit son niveau d'immunodépression, et notamment en cas de non amélioration sous bêta-lactamines. Un diagnostic précoce par l'antigénurie et une antibiothérapie adaptée doit permettre d'obtenir un pronostic favorableLegionellosis is a serious and still too often underestimated disease, in particular at the immuno-deprissed patients. Seldom described at the patient infected by the virus of the human immunodeficiency before the era of the effective antiretroviral treatments, it occurred among very immuno-deprissed patients. Responsible for complicated forms of lung diseases, his prognosis was reserved. This descriptive retrospective study compared the clinical and progressive characteristics of the legionellosis between two cohort of patients infected or not by the HIV, hospitalized at the Henri Mondor hospital between 1998 and 2004. The HIV negative cohort is composed of 36 patients, of which 60% were immuno-depressed. The HIV positive cohort was composed of 6 patients under effective anti-retroviral treatment, little immuno-dépressed (average rate of T CD4+ lymphocytes = 479 +- 144 /mm3). None was under opportunists diseases preventive prophylaxis. In HIV positive patients, the diagnosis was constantly posed by the Legionella urine antigen testing. The clinical presentation and the evolution of HIV positive cohort were comparable with those of HIV negative patients.The prognosis of the affection among HIV positive patients was better than that of the HIV negative immuno-dépressed patients, among whom were noted the most serious forms, even mortals. In spite of a reduction in preventive prophylaxis by trimethoprime-sulfamethoxazol in the population of the patients infected by the HIV, it was not observed of increase in the legionellosis among these patients, which suggests that the immune restoration by the antiretroviral treatments confers at least an partial immunity against this s disease. Legionellosis must nevertheless be required in front of any bacterial pneumonia in HIV positive patient, whatever his immuno-depression level, and in particular in the event of non-improvement under beta-lactamines. An early diagnosis by the urine antigen testing and an adapted antibiotic therapy must make it possible to obtain a favourable prognosisPARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Bactériémies à Campylobacter fetus (facteurs de risque, caractéristiques cliniques et évolutives à propos de 21 cas)

Après quelques généralités sur le genre Campylobacter, il est rapporté 21 cas de bactériémie à Campylobacter fetus, les facteurs de risque de survenue d une telle maladie et les caractéristiques cliniques et évolutives. Les résultats sont les suivants. L âge médian des patients était de 78 ans. La majorité des patients présentaient une immunodépression (71%) et/ou un terrain cardiovasculaire à risque (53%). La principale présentation clinique était la fièvre, parfois isolée (38% des cas) ou associée à des signes extra digestifs (62% des cas) notamment des infections d anévrisme de l aorte abdominale (24% des cas) ou des cellulites (19% des cas). Le traitement antibiotique était principalement axé sur l amoxicilline-acide clavulanique (57%) ou l imipénème (21%), avec une durée médiane de traitement de 28 jours. Une évolution favorable était notée dans 62% des cas. Le décès directement imputable à l infection a été observé pour 3 patients, dû à la rupture d un anévrisme infecté ou à la récidive d une bactériémie avec choc septique. Tous les patients traités initialement par imipénème ont eu une évolution favorable. Cette étude apporte donc la preuve que la bactériémie à C fetus doit être suspectée chez les patients âgés présentant de la fièvre, une immunodépression et une atteinte cardiovasculaire. L imipénème semble être la molécule la plus active, spécialement dans les formes les plus graves.PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A new endpoint definition improved clinical relevance and statistical power in a vaccine trial.: New endpoint formulation for vaccine trials

International audienceOBJECTIVE: Endpoints used for the evaluation of immunogenicity in vaccine trials are often the proportion of individuals with immune response or geometric means of antibody concentrations for each serotype. When a vaccine includes several types of the same species, we illustrate how an endpoint combining all responses may improve clinical relevance and statistical power. STUDY DESIGN AND SETTINGS: The motivating example was the ANRS 114 Pneumovac trial where the effect of two vaccine strategies against Streptococcus pneumoniae was assessed in adults infected by the Human Immunodeficiency Virus. The power associated with several endpoints was calculated in the example and in simulations. A new endpoint based on four ordered levels is formulated and analyzed by using a proportional odds model. RESULTS AND CONCLUSION: The analysis of this new endpoint led to an odds ratio allowing detection of improvement and detriment. In the simulation study, this endpoint was associated with the largest statistical power by increasing the amount of information used as compared with usual endpoints. We recommend this new endpoint formulation in the formal development of a new vaccination regimen, whenever applicable

Outils de diagnostic, épidémiologie d’Alternaria dauci sur carotte porte-graine et méthodes de lutte

Alternaria dauci est un pathogène affectant fréquemment les semences de carotte avec des répercussions sur la faculté germinative. Les travaux menés ont permis la mise au point d’outils de détection basés sur des amorces PCR des régions ITS, presque exclusivement spécifiques de l’espèce Alternaria dauci. Des outils d’identification intraspécifiques à partir des régions IGS et de loci micro satellites ont également pu être mis au point, et mettre en évidence la grande variabilité génétique de l’espèce A. dauci. Au plan épidémiologique, une clé d’identification des brûlures foliaires a été établie. Il a pu être démontré que la plante est sensible au pathogène quel que soit son stade de développement, mais les conditions climatiques propices au développement du pathogène n’ont pu être clairement établies. L’étude de l’efficacité de produits fongicides a permis de mettre en avant 3 spécialités efficaces (SIGNUM, AMISTAR et dans une moindre mesure TWIST), et de démontrer l’existence de souches résistantes à l’iprodione. Enfin, le modèle Tomcast, adapté pour l’alternariose sur carotte par le CTIFL, a fait l’objet de premiers tests d’application sur porte-graine au cours de ce programme. Ce modèle est actuellement en cours de développement.Alternaria dauci is a fungal seed-borne pathogen responsible for the leaf blight disease on carrots that has a negative impact on seed germination efficiency. In this study, molecular diagnostic tools based on PCR amplification of the ITS region with species-specific primers were developed. Polymorphism analyses at several microsatellite loci and in the intergenic spacer (IGS) sequence revealed a high genetic diversity within the species A. dauci. From an epidemiological point of view, an identification key for leaf blight was established. It has been shown that the host plant is susceptible to fungal pathogen infection irrespective of its developmental stage but climatic conditions favouring disease development could not be clearly established. Screening different fungicide treatments revealed that three specialities were efficient to control the disease (SIGNUM, AMISTAR, and to a lesser extent TWIST) but iprodione-resistant strains were identified. Preliminary tests of the Tomcast model, adapted to carrot Alternaria leaf blight (CTIFL), were conducted in seed production during this project. Additional tests using this model are currently performed

Protracted Outbreak of Multidrug-Resistant Acinetobacter baumannii after Intercontinental Transfer of Colonized Patients

International audienc

Defining standard and high dosages for β-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study

International audienceBackground: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).Methods: Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.Results: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.Conclusions: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary

Temocillin versus carbapenems for urinary tract infection due to ESBL-producing Enterobacteriaceae: a multicenter matched case-control study.

International audienceObjectives: We aim to compare the efficacy of temocillin to carbapenems for ESBL-E UTI.Methods: We conducted a multicenter retrospective case-control study of adults with ESBL-E UTI between January-2015 and October-2019. Cases received temocillin ≥50% of the effective antibiotic therapy duration. Control exclusively received carbapenem. They were statistically matched (1:1 ratio) on period, sex, and age. The clinical cure at the end of antibiotic therapy was analyzed using conditional logistic regression.Results: We matched 72 temocillin cases to 72 carbapenem controls. Most (67%) were male, aged 69.4-years in median, 81 (56%) were immunocompromised, including 44 (31%) solid organ transplant recipients (SOT). There was no difference between cases and controls for baseline characteristics and microorganisms involved: K.pneumoniae in 59 (41%), E.coli in 57 (40%), and Enterobacter spp. in 24 (17%). The median time from admission to effective antibiotic therapy was 0-days [0-2]. Among cases, first-line antibiotic therapy (≤72 hours) was temocillin in 6 (8%) and carbapenems in 39 (54%). Temocillin was given at the median daily dose of 4g [2], [3], [4], after 3-days [2], [3], [4], [5] of carbapenems. Patients received temocillin for 81% [70-93] of the effective antibiotic course duration during 11-days [8], [9], [10], [11], [12], [13], [14]. The effective antibiotic duration was similar in cases and controls (p-value=0.067). Clinical cure at the end of the antibiotic therapy was 94% (68/72) in cases versus 99% (71/72) in controls (p-value=0.206), without difference among immunocompromised and SOT patients (p-value>0.050).Conclusions: Temocillin effectively relays beta-lactams, including carbapenems, to treat (complicated) ESBL-E UTI. Its efficacy is consistent among kidney transplant recipients

Protracted outbreak of multidrug-resistant Acinetobacter baumannii after intercontinental transfer of colonized patients

To describe the course and management of a protracted outbreak after intercontinental transfer of 2 patients colonized with multidrug-resistant Acinetobacter baumannii (MDRAB)

Protracted Outbreak of Multidrug-Resistant Acinetobacter baumannii after Intercontinental Transfer of Colonized Patients

International audienc

Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum β-lactamase-producing Enterobacteriaceae

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are endemic pathogens worldwide. Infection with ESBL-PE may be associated with inadequate antibiotic therapy and a poor outcome. However, risk factors for ESBL-PE community-acquired infections are ill-defined. An observational multicentre study was performed in 50 hospitals to identify the prevalence of and risk factors for community-acquired ESBL-PE bacteraemia. All patients presenting with community-onset Enterobacteriaceae bacteraemia were recorded over a 2-month period (between June and November 2013). Risk factors and 14-day outcomes of patients were investigated. Among 682 Enterobacteriaceae bacteraemia episodes recorded, 58 (8.5%) were caused by ESBL-PE. The most frequent species isolated were Escherichia coli (537; 76.7%) and Klebsiella spp. (68; 9.7%), of which 49 (9.1%) and 8 (11.8%), respectively, were ESBL-producers. Most ESBL-PE episodes were healthcare-associated, and only 22 (38%) were apparently community-acquired. The main risk factor for community-acquired ESBL-PE bacteraemia was a prior hospital stay of ≥5 days within the past year. The overall 14-day survival was 90%; only 4 (6.9%) of 58 patients with ESBL-PE bacteraemia died. Inadequate initial antibiotic therapy was administered to 55% of patients with ESBL-PE bacteraemia but was not associated with increased 14-day mortality. Although many patients had community-onset ESBL-PE bacteraemia, almost two-thirds of the episodes were actually healthcare-associated, and true community-acquired ESBL-PE bacteraemia remains rare. In our essentially non-severely ill population, inappropriate initial therapy was not associated with a higher risk of mortality