Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency

International audienceIn immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk

Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis.

International audienceThe IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults:A Consensus Statement Regarding Initial Strategies

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia

Revue des endocardites à entérocoque, focus sur l'utilisation des aminosides

Contexte: l'EI à entérocoque requière un traitement prolongé associant l'amoxicilline et la gentamicine; des données concernant leur utilisation en dose unique journalière manquent dans cette indication. Objectifs: décrire les caractéristiques des EI à entérocoque, évaluer l'efficacité et la toxicité des aminosides en DUJ. Méthode: étude rétrospective des EI à entérocoque hospitalisées entre 2000 et 2010. Résultats: 52 patients ont été inclus. E. faecalis était le germe le plus fréquent. L'âge moyen était de 72.6 ans, 73% des patients présentaient au mois une co-morbidité. La gentamicine était administrée en dose unique journalière dans 72% des cas. 2 patients sont décédés pendant l'hospitalisation, 3 ont rechuté et 6 patients sont décédés dans l'année suivante, soit une mortalité globale de 15.3%. Conclusion: l'administration de la gentamicine en DUJ est efficace dans le traitement des endocardites à entérocoque, y compris chez des sujets âgés et fragilisés.Background: enterococcal IE require prolonged therapy combining amoxicillin and gentamicin. Data regarding extend-interval aminoglycoside dosing (EIAD) are lacking in this setting. Objectives: To describe the characteristics of enterococcal IE, evaluate the efficacy and toxicity of aminoglycosides in AIAD. Method: retrospective study of enterococcal IE hospitalized between 2000 and 2010. Results: 52 patients were included. E. faecalis was the most frequent organism isolated. Mean age was 72.6 years, and 73% of patients had at least one co-morbidity. Treatment combined an antibiotic active on the bacterial wall and an aminoglycoside; gentamicin was administered at EIAD with feedback based on the residual rate in majority of cases(72%) . Two patients died during hospitalization, 3 relapsed and six patients died within the year following the IE, with an overall mortality of 15.3%. Conclusion: gentamicin used with EIAD is effecacious for enterococcal IE, even in elderly.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Pourquoi le bon usage est-il particulièrement important pour la classe thérapeutique des anti-infectieux ?

National audienc

Prescription et surveillance des antibiotiques [Antibiotic prescription and surveillance]

International audienceno abstrac

Prescription et surveillance des anti-infectieux chez l’adulte et l’enfant (voir item 330) - Partie 1 : Antibiotiques

National audienc

Prescription et surveillance des anti-infectieux chez l’adulte et l’enfant (voir item 330) [2] - Partie 2 : Antiviraux, antiparasitaires, antifongiques

National audienc

Borrélioses et fièvres récurrentes

National audienceBorrélioses et fièvres récurrentes Les borrélioses récurrentes (br) ou fièvres récurrentes sont dues à des bactéries du genre borrelia, de la famille des spirochètes, transmises à l’homme par des arthro¬podes vecteurs (poux de corps, tiques molles, et tiques dures pour l’une d’entre elles). La br à poux est cosmo¬polite et transmise lors d’épidémies survenant dans le contexte de crises majeures (promiscuité, conditions d’hygiène précaires, crise alimentaire, etc.). Les br à tiques se répartissent par région, selon la borrelia en cause et la distribution géographique de leur tique vec¬trice. Le temps d’incubation varie de 3 à 20jours. La première phase fébrile dure 3jours (1-14jours), suivie d’une phase d’apyrexie avec persistance des autres signes cliniques (rash cutané, pétéchies, céphalées in¬tenses, agitation, polyarthromyalgies, douleurs abdomi¬nales, nausées/vomissements, etc.). La récurrence de la fièvre décrit une périodicité de 7jours en moyenne. La bactériémie est abondante lors des pics fébriles, permet¬tant de poser un diagnostic par examen direct en mi¬croscopie, pcr borrelia ou culture sur milieu spécial, quand celle-ci est possible. Le traitement repose sur la doxycycline, sauf pour les formes neurologiques (ceftriaxone). Le taux de mortalité varie de 2 à 5 % selon la borrelia incriminée. L’évolution est le plus souvent favorable après traitement

Intérêt diagnostic des TEP-TDM en infectiologie [Contribution of 18fluoro-deoxyglucose PET/CT for the diagnosis of infectious diseases.]

International audienceThe diagnosis of some infectious diseases is sometimes difficult to make and new diagnostic tools have been regularly assessed to that end. 18fluoro-deoxyglucose ((18)FDG) positron-emission tomography (PET) coupled with computed tomography (CT) is one of these new procedures. It has been evaluated for numerous infectious diseases with uneven results. A literature review allowed drawing some conclusions. First, (18)FDG-PET/CT is not currently a first-line procedure for infectious diseases. Second, it has proved useful for the evaluation of patients presenting with fever of unknown origin (FUO). Its negative predictive value is 100%: the symptoms of patients experiencing FUO with negative first-line investigations and a negative (18)FDG-PET/CT will almost always spontaneously disappear. Third, (18)FDG-PET/CT also seems to be contributive for the diagnosis of vascular prosthesis infections or osteomyelitis. Fourth, it has promising results for patients presenting with infective endocarditis, especially for secondary infectious foci, or for patients presenting with suspected infection of pacemakers or implanted defibrillator; but results are still preliminary and must be confirmed. Finally(18)FDG-PET/CT cannot be recommended yet for other infectious diseases due to lack of published data