Comparison of albicans vs. non-albicans candidemia in French intensive care units

The AmarCand Study Group (ICU physicians): Drs. Allaouchiche (Lyon), Amigues (Montpellier), Ausseur (Saint Herblain), Azoulay (Paris), Badet (Lyon), Baldesi (Aix-en-Provence), Bastien (Bron), Baudin (Paris), Bayle (Lyon), Bazin (Clermont-Ferrand), Benayoun (Clichy), Blondeau (Roubaix), Bodin (Paris), Bollaert (Nancy), Bonadona (La Tronche), Bonnaire (Aulnay Sous Bois), Bonnivard (Montauban), Borne (Paris), Brabet (Montpellier), Branche (Lyon), Braud (Rouen), Bret (Lyon), Bretonnière (Nantes), Brocas (Evry), Brun (Bron), Bruneel (Versailles), Canevet (Armentières), Cantais (Toulon Armées), Carlet (Paris), Charbonneau (Caen), Charles (Dijon), Chastagner (Chamberry), Corne (Montpellier), Courte (Saint-Brieuc), Cousson (Reims), Cren (Morlaix), Diconne (Saint Etienne), Drouet (Saint-Denis), Dube (Angers), Duguet (Paris), Dulbecco (Antibes), Dumenil (Clamart), Dupont (Amiens), Durand (Grenoble), Durand-Gasselin (Toulon), Durocher (Lille), Fangio (Poissy), Fattouh (Mulhouse), Favier (Metz Armées), Fieux (Paris), Fleureau (Pessac), Freys (Strasbourg), Fulgencio (Paris), Gally (Mulhouse), Garnaud (Orléans), Garot (Tours), Gilhodes (Créteil), Girault (Rouen), Gouin (Marseille), Gouin (Rouen), Guidon (Marseille), Hérault (Grenoble), Hyvernat (Nice), Jobard (Monaco), Jospe (Saint Etienne), Kaidomar (Fréjus), Karoubi (Bobigny), Kherchache (Agen), Lacherade (Poissy), Lakermi (Paris), Lambiotte (Maubeuge), Lamia (Le Kremlin-Bicêtre), Lasocki (Paris), Launoy (Strasbourg), Le Guillou (Paris), Lefort (Saint-Denis), Lefrant (Nîmes), Lemaire (Roubaix), Lepape (Pierre-Bénite), Lepoutre (Lomme), Leroy (Lille), Leroy (Tourcoing), Loriferne (Bry-sur-Marne), Mahe (Nantes), Mandin (Gap), Marighy (Saint- Denis), Mathieu (Lille), Mathonnet (Paris), Megarbane (Paris), Mercat (Angers), Michel (Saint Herblain), Michelet (Marseille), Mimoz (Poitiers), Mohammedi (Lyon), Mouquet (Paris), Mourvillier (Paris), Navellou (Besançon), Novara (Paris), Obadia (Montreuil), Perrigault (Montpellier), Perrin (Marseille), Petit (Valence), Poussel (Metz), Rahmani (Strasbourg), Renard (La Roche sur Yon), Robert (Poitiers), Robert (Lyon), Saliba (Villejuif ), Sannini (Marseille), Santré (Annecy), Seguin (Rennes), Souweine (Clermont-Ferrand), Trouillet (Paris), Valentin (Besançon), Volatron (Rennes), Voltz (Vandoeuvre les Nancy), Winer (Saint Pierre), and Winnock (Bordeaux).International audienceINTRODUCTION: Candidemia raises numerous therapeutic issues for intensive care physicians. Epidemiological data that could guide the choice of initial therapy are still required. This analysis sought to compare the characteristics of intensive care unit (ICU) patients with candidemia due to non-albicans Candida species with those of ICU patients with candidemia due to Candida albicans. METHODS: A prospective, observational, multicenter, French study was conducted from October 2005 to May 2006. Patients exhibiting candidemia developed during ICU stay and exclusively due either to one or more non-albicans Candida species or to C. albicans were selected. The data collected included patient characteristics on ICU admission and at the onset of candidemia. RESULTS: Among the 136 patients analyzed, 78 (57.4%) had candidemia caused by C. albicans. These patients had earlier onset of infection (11.1 +/- 14.2 days after ICU admission vs. 17.4 +/- 17.7, p = 0.02), higher severity scores on ICU admission (SOFA: 10.4 +/- 4.7 vs. 8.6 +/- 4.6, p = 0.03; SAPS II: 57.4 +/- 22.8 vs. 48.7 +/- 15.5, P = 0.015), and were less often neutropenic (2.6% vs. 12%, p = 0.04) than patients with candidemia due to non-albicans Candida species. CONCLUSIONS: Although patients infected with Candida albicans differed from patients infected with non-albicans Candida species for a few characteristics, no clinical factor appeared pertinent enough to guide the choice of empirical antifungal therapy in ICU

Endogenous IL-33 Accelerates Metacestode Growth during Late-Stage Alveolar Echinococcosis.

During the course of the infectious disease alveolar echinococcosis (AE), the larval stage of Echinococcus multilocularis develops in the liver, where an initial Th1/Th17 immune response may allow its elimination in resistant individuals. In patients susceptible to infection and disease, the Th2 response initiates later, inducing tolerance to the parasite. The role of interleukin 33 (IL-33), an alarmin released during necrosis and known to drive a Th2 immune response, has not yet been described during AE. Wild-type (WT) and IL-33-/- C57BL/6J mice were infected by peritoneal inoculation with E. multilocularis metacestodes and euthanized 4 months later, and their immune response were analyzed. Immunofluorescence staining and IL-33 enzyme-linked immunosorbent assay (ELISA) were also performed on liver samples from human patients with AE. Overall, metacestode lesions were smaller in IL-33-/- mice than in WT mice. IL-33 was detected in periparasitic tissues, but not in mouse or human serum. In infected mice, endogenous IL-33 modified peritoneal macrophage polarization and cytokine profiles. Th2 cytokine concentrations were positively correlated with parasite mass in WT mice, but not in IL-33-/- mice. In human AE patients, IL-33 concentrations were higher in parasitic tissues than in distant liver parenchyma. The main sources of IL-33 were CD31+ endothelial cells of the neovasculature, present within lymphoid periparasitic infiltrates together with FOXP3+ Tregs. In the murine model, periparasitic IL-33 correlated with accelerated parasite growth putatively through the polarization of M2-like macrophages and release of immunosuppressive cytokines IL-10 and transforming growth factor β1 (TGF-β1). We concluded that IL-33 is a key alarmin in AE that contributes to the tolerogenic effect of systemic Th2 cytokines. IMPORTANCE Infection with the metacestode stage of Echinococcus multilocularis, known as alveolar echinococcosis, is the most severe cestodosis worldwide. However, less than 1% of exposed individuals, in which the immune system is unable to control the parasite, develop the disease. The factors responsible for this interindividual variability are not fully understood. In this in vivo study comparing wild-type and IL-33-/- infected mice, together with data from human clinical samples, we determined that IL-33, an alarmin released following tissue injury and involved in the pathogenesis of cancer and asthma, accelerates the progression of the disease by modulating the periparasitic microenvironment. This suggests that targeting IL-33 could be of interest for the management of patients with AE, and that IL-33 polymorphisms could be responsible for increased susceptibility to AE

Comparison of three commercial multiplex PCR assays for the diagnosis of intestinal protozoa

Although microscopic examination of stool samples remains the reference method for the diagnosis of intestinal protozoal infections, these techniques are time-consuming and require operators who are experienced and well trained. Molecular biology seems to offer performances at least equivalent in terms of sensitivity and specificity for certain parasites. This study aimed to compare three multiplex PCR assays on 93 prospectively collected positive stools (prospective cohort) and a panel of 12 more Cryptosporidium-positive samples (Cryptosporidium panel). On the prospective cohort, the sensitivity was 89%, 64% and 41% for Giardia sp. detection for BD MaxTM, G-DiaParaTM and RIDA®GENE, respectively and 75%, 100% and 100% for C. parvum/hominis detection. The sensitivity of the RIDA®GENE assay for all Cryptosporidium species was 100%, and for D. fragilis 71%. All the techniques obtained the same results for E. histolytica detection, with one positive sample. All species in the Cryptosporidium panel were identified by the RIDA®GENE PCR. The BD MaxTM and G-DiaParaTM assays detected only C. parvum/hominis with the exception of one positive sample for C. meleagridis. No assay showed satisfactory results for all parasites simultaneously, and the DNA extraction seems to be the critical step. More studies are needed to standardize this procedure

Exposition domiciliaire aux moisissures : quel impact sur le statut aspergillaire du patient atteint de mucoviscidose ?

National audienc

Near-Fatal Multiple Organ Dysfunction Syndrome Induced by Plasmodium malariae

International audienc

Invariant NKT Cells Drive Hepatic Cytokinic Microenvironment Favoring Efficient Granuloma Formation and Early Control of Leishmania donovani Infection

The development of inflammatory granulomas around infected Kupffer cells is necessary for hepatic parasite clearance during visceral leishmaniasis. Invariant NKT (iNKT) cells are predominant T cells in the mouse liver and can synthesize large quantities of IL-4 and IFN-γ, two cytokines involved in granuloma formation. This study analyzed the role of iNKT cells in the hepatic immune response during Leishmania donovani infection, using a murine model of wild-type (WT) and iNKT cell-deficient (Jα18-/-) C57BL/6 mice sacrificed 15, 30 or 60 days post-infection. We recorded hepatic parasite loads, cytokine expression, and analyzed granulomatous response by immunohistochemistry and hepatic immune cell infiltration by flow cytometry. Whereas WT animals rapidly controlled the infection and developed an inflammatory response associated with a massive influx of iNKT cells observed by flow cytometry, Jα18-/- mice had significantly higher parasitic loads on all time points. This lack of control of parasite burden was associated with a delay in granuloma maturation (28.1% of large granulomas at day 60 versus 50.7% in WT). Cytokine transcriptome analysis showed that mRNA of 90/101 genes encoding chemokines, cytokines and their receptors, was underexpressed in Jα18-/- mice. Detection of IL-4 and TNF-α by ELISA in liver extracts was also significantly lower in Jα18-/- mice. Consistent with flow cytometry analysis, cytokinome profile in WT mice showed a bias of expression towards T cell-chemoattractant chemokines on D15, and displayed a switch towards expression of granulocytes and/or monocytes -chemoattractant chemokines on D60. In Jα18-/- mice, the significantly lower expression of CXCL5, MIP-2 and CCL2 mRNA was correlated with a defect in myeloperoxidase positive-cell attraction observed by immunohistochemistry and with a lower granulocyte and monocyte infiltration in the liver, as shown by flow cytometry. These data indicate that iNKT cells play a role in early and sustained pro-inflammatory cytokine response warranting efficient organization of hepatic granulomas and parasite clearance

Recurrent American Cutaneous Leishmaniasis

International audienc

Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement.

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity to conventional culture techniques, serologic tests, and PCR-based assays in patients undergoing antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody, and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.S

Clinical Impact of Antifungal Susceptibility, Biofilm Formation and Mannoside Expression of Candida Yeasts on the Outcome of Invasive Candidiasis in ICU: An Ancillary Study on the Prospective AmarCAND2 Cohort

Background: The link between Candida phenotypical characteristics and invasive candidiasis (IC) prognosis is still partially unknown.Methods:Candida strains isolated during the AmarCAND2 study were centrally analyzed for species identification, antifungal susceptibility, biofilm formation, and expression of surface and glycoconjugate mannosides. Correlation between these phenotypical features and patient outcome was sought using a multivariable Cox survival model.Results:Candida albicans was predominant (65.4%, n = 285), with a mortality rate significantly lower than that in patients with non-albicans strains [HR 0.67 (0.46–1.00), p = 0.048]. The rate of fluconazole-resistant strains was low (C. albicans and Candida glabrata: 3.5 and 6.2%, respectively) as well as caspofungin-resistant ones (1 and 3.1%, respectively). Early biofilm formation was less frequent among C. albicans (45.4%) than among non-albicans (81.2%). While the strains of C. albicans showed variable levels of surface mannosides expression, strains isolated from candidemia exhibited a high expression of β-man, which was correlated with an increased mortality (p = 0.02).Conclusion:Candida albicans IC were associated with lower mortality, and with strains that exhibited less frequently early biofilm formation than non-albicans strains. A high expression of β-man was associated with increased IC mortality. Further studies are warranted to confirm this data and to evaluate other virulence factors in yeasts

Double Infection with Leishmania tropica and L. Major in an Hiv patient controlled with high doses of amphotericin B

We present a unique case of disseminated Leishmaniasis in an HIV patient. Two different Leishmania species were identified by genomic sequencing in both bone marrow and skin. The Leishmania infection could be suppressed but not cured, despite a high dose of amphotericin B of nearly 65 g over more than 6 years