Single dose pharmacodynamics of amphotericin B against Aspergillus species in an in vitro pharmacokinetic/pharmacodynamic model

Conventional MIC testing of amphotericin B results in narrow MIC ranges challenging the detection of resistant strains. In order to discern amphotericin B pharmacodynamics, the in vitro activity of amphotericin B was studied against Aspergillus isolates with the same MIC with a new in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that simulates amphotericin B human plasma levels. Clinical isolates of A. fumigatus, A. terreus and A flavus with the same CLSI modal MICs of 1 mg/l were exposed to amphotericin B concentrations following the plasma concentration-time profile after single bolus administration with Cmax 0.6, 1.2, 2.4 and 4.8 mg/L. Fungal growth was monitored up to 72h based on galactomannan production. Complete growth inhibition was observed only against A. fumigatus with amphotericin B Cmax ≥2.4 mg/L. At lower Cmaxs 0.6 and 1.2 mg/L, a significant growth delay of 34h and 52h was observed, respectively (pA flavus>A. terreus in the in vitro PK/PD model possibly reflecting the different concentration- and time-dependent inhibitory/killing activities amphotericin B exerting against these species

Saccharomyces boulardii fungaemia in an intensive care unit patient treated with caspofungin

We describe a case of Saccharomyces boulardii fugaemia in a critically ill patient with septic shock treated with a probiotic agent containing this yeast. We attributed this fugaemia to gut translocation. Our use of caspofugin yielded excellent results

Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox\u27s proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P\u3c0.0001) and its severity (P\u3c0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden\u27s index) predicted future risk of MI (hazard ratio [HR]=3.2; P\u3c0.0001), cardiac death (HR=2.62; P\u3c0.0001), and the combined endpoint of death and MI (HR=1.9; P\u3c0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database - the quality controlled standard tool for routine identification of human and animal pathogenic fungi

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.This study was supported by an National Health and Medical Research Council of Australia (NH&MRC) grant [#APP1031952] to W Meyer, S Chen, V Robert, and D Ellis; CNPq [350338/2000-0] and FAPERJ [E-26/103.157/2011] grants to RM Zancope-Oliveira; CNPq [308011/2010-4] and FAPESP [2007/08575-1] Fundacao de Amparo Pesquisa do Estado de So Paulo (FAPESP) grants to AL Colombo; PEst-OE/BIA/UI4050/2014 from Fundacao para a Ciencia e Tecnologia (FCT) to C Pais; the Belgian Science Policy Office (Belspo) to BCCM/IHEM; the MEXBOL program of CONACyT-Mexico, [ref. number: 1228961 to ML Taylor and [122481] to C Toriello; the Institut Pasteur and Institut de Veil le Sanitaire to F Dromer and D Garcia-Hermoso; and the grants from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and the Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) to CM de Almeida Soares and JA Parente Rocha. I Arthur would like to thank G Cherian, A Higgins and the staff of the Molecular Diagnostics Laboratory, Division of Microbiology and Infectious Diseases, Path West, QEII Medial Centre. Dromer would like to thank for the technical help of the sequencing facility and specifically that of I, Diancourt, A-S Delannoy-Vieillard, J-M Thiberge (Genotyping of Pathogens and Public Health, Institut Pasteur). RM Zancope-Oliveira would like to thank the Genomic/DNA Sequencing Platform at Fundacao Oswaldo Cruz-PDTIS/FIOCRUZ [RPT01A], Brazil for the sequencing. B Robbertse and CL Schoch acknowledge support from the Intramural Research Program of the NIH, National Library of Medicine. T Sorrell's work is funded by the NH&MRC of Australia; she is a Sydney Medical School Foundation Fellow.info:eu-repo/semantics/publishedVersio

CANDIDA ALBICANS SEROTYPES A AND B: COMPARATIVE STUDY OF THEIR BIOCHEMICAL AND GENETIC PROPERTIES AND DETERMINATION OF THE MINIMAL INHIBITORY CONCENTRATIONS OF EIGHT ANTIFUNGAL AGENTS

A COMPARATIVE STUDY OF THE TWO MAJOR SEROTYPES OF C. ALBICANS A AND B (CA-A, CA-B), HAS SHOWN THAT THERE ARE BIOCHEMICAL MORPHOLOGICAL AND GENETIC DIFFERENCESWHICH ACCOUNT FOR THEIR RELATIVE SUSCEPTIBILITY TO THE POLYENES, 5-FLUOROCYTOSINE (5-FC) AND TO FIVE (5) IMIDAZOLE DERIVATIVES IN VITRO. THE STUDY INCLUDED 491 CLINICAL ISOLATES OF CA-A AND 505 CA-B STRAINS ISOLATED FROM IMMUNOCOMPROMISED HOSTS OR FROM PATIENTS PREVIOUSLY TREATED WITH KETOCONAZOLE (KTZ) SHOWED RESISTANCE TO AMPHOTERICINE B (AMP-B). OF THE 996 ISOLATES OF CA-A AND CA-B ONLY 7SHOWED INCREASED MIC'S TO THE POLYENES. SEROTYPE B WAS A FREQUENT AETIOLOGIC AGENT OF SYSTEMIC CANDIDIASIS (50%) RECURRING VAGINITIS (68.8%) AND CANDIDIASIS THE URINARY TRACT (43%). COMPARATIVE STUDY, USING STANDARD MIC PROCEDURE ON SOLID MEDIA AND COMMERCIALLY AVAILABLE MEDIA WITH ANTIFUNGAL DISCS, SHOWED THAT CA-B STRAINS FREQUENTLY APPEAR AS "PARTIALLY RESISTANT" TO THE IMIDAZOLE DERIVATIVES WHEN TESTED WITH THE LATTER METHOD. THIS CLASSIFICATION DOES NOT, HOWEVER, CORRESPOND TO THE TRUE MIC VALUE WHICH CATEGORISES THEM AS "SENSITIVE". THE RESULTS ALSO INDICATE THAT PHENOTYPIC RESISTANCE TO THE ANTIFUNGAL AGENTS IS INFLUENCED BY THE GROWTH PHASE OF C. ALBICANS (I.E. YEAST, MYCELIAL, LOGARITHMIC, STATIONARY PHASE). (SHORTENED)ΣΥΓΚΡΙΤΙΚΗ ΜΕΛΕΤΗ ΤΩΝ ΔΥΟ ΚΥΡΙΩΝ ΟΡΟΤΥΠΩΝ 491 ΚΛΙΝΙΚΩΝ ΣΤΕΛΕΧΩΝ CANDIDA ALBICANS-A (CA-A) ΚΑΙ 505 CA-B ΚΑΙ ΕΔΕΙΞΑΝ ΟΤΙ ΥΠΑΡΧΟΥΝ ΓΕΝΕΤΙΚΕΣ ΒΙΟΧΗΜΙΚΕΣ ΚΑΙ ΜΟΡΦΟΛΟΓΙΚΕΣ ΔΙΑΦΟΡΕΣ, ΠΟΥ ΡΥΘΜΙΖΟΥΝ ΤΗΝ IN VITRO ΑΝΤΟΧΗ ΤΟΥΣ ΣΤΙΣ ΠΟΛΥΕΝΙΚΕΣ ΜΑΚΡΟΛΙΔΕΣ, ΤΗΝ 5- FLUOROCYTOSINE (5-FC) ΚΑΙ ΣΕ ΠΕΝΤΕ (5) ΠΑΡΑΓΩΓΑ ΤΩΝ ΙΜΙΔΑΖΟΛΩΝ. Η ΦΑΙΝΟΤΥΠΙΚΗ ΑΝΤΟΧΗ ΤΩΝ CA-A ΚΑΙ CA-B ΕΠΗΡΕΑΖΕΤΑΙ ΑΠΟ ΤΗ ΦΑΣΗ ΑΝΑΠΤΥΞΗΣ ΤΟΥΣ (ΣΤΑΘΕΡΗ/ΛΟΓΑΡΙΘΜΙΚΗ), ΤΗ ΦΑΣΗ ΤΟΥ ΒΙΟΛΟΓΙΚΟΥ ΚΥΚΛΟΥ (ΜΥΚΗΤΥΛΛΙΟ/ΒΛΑΣΤΟΚΥΤΤΑΡΟ), ΤΟ ΟΡΟΤΥΠΟ ΚΑΙ ΑΠΟ ΤΙΣ ΕΡΓΑΣΤΗΡΙΑΚΕΣ ΜΕΘΟΔΟΥΣ ΠΟΥ ΧΡΗΣΙΜΟΠΟΙΟΥΝΤΑΙ ΓΙΑ ΤΟΝ ΠΡΟΣΔΙΟΡΙΣΜΟ ΤΗΣ ΑΝΤΟΧΗΣ ΣΤΑ ΑΝΤΙΜΥΚΗΤΙΑΚΑ. Η ΓΕΝΟΤΥΠΙΚΗ ΑΝΑΛΥΣΗ ΤΩΝ ΔΥΟ ΟΡΟΤΥΠΩΝ, ΩΣ ΠΡΟΣ ΤΗΝ ΑΝΤΟΧΗ ΤΟΥΣ ΣΤΗΝ 5-FC, ΕΔΕΙΞΕ ΑΥΞΗΜΕΝΗ ΣΥΧΝΟΤΗΤΑ ΤΩΝ F/F ΚΛΩΝΩΝ (ΜΕΤΡΙΑ ΕΥΑΙΣΘΗΤΩΝ) ΚΑΙ F/F (ΑΝΘΕΚΤΙΚΩΝ) ΓΙΑ ΤΑ ΣΤΕΛΕΧΗ CA-B. Ο ΕΛΕΓΧΟΣ ΔΑΥΞΟΤΡΟΦΙΑΣ ΣΕ ΑΜΙΝΟΞΕΑ ΕΔΕΙΞΕ ΟΤΙ ΤΟ ΓΟΝΙΔΙΟ ΑΝΤΟΧΗΣ ΣΤΗΝ 5-FC ΣΥΝΔΕΕΤΑΙ ΜΕ ΤΟ ΑΛΛΗΛΟΜΟΡΦΟ ΓΟΝΙΔΙΟ ΑΥΞΟΤΡΟΦΙΑΣ ΣΤΗ ΛΥΣΙΝΗ. Η ΥΨΗΛΗΣ ΠΙΕΣΗΣ ΧΡΩΜΑΤΟΓΡΑΦΙΚΗ ΑΝΑΛΥΣΗ ΣΤΕΡΟΛΩΝ ΤΗΣ ΚΥΤΤΑΡΙΚΗΣ ΜΕΜΒΡΑΝΗΣ 334 ΣΤΕΛΕΧΩΝ CA-A ΚΑΙ CA-B ΕΔΕΙΞΕ ΒΙΟΣΥΝΘΕΣΗ ΣΗΜΑΝΤΙΚΑ ΠΕΡΙΣΣΟΤΕΡΩΝ ΟΛΙΚΩΝ ΣΤΕΡΟΛΩΝ (Ρ<0.05) ΣΤΟΝ ΟΡΟΤΥΠΟ Β. ΕΠΙΣΗΣ ΔΙΑΔΟΧΙΚΗ ΕΚΘΕΣΗ ΤΩΝ ΣΤΕΛΕΧΩΝ ΣΕ KETOCONAZOLE (ΚΤΖ) KAI AMPHOTERICIN-B (AMP-B) ΠΡΟΚΑΛΕΙ ΣΗΜΑΝΤΙΚΗ ΜΕΙΩΣΗ ΤΗΣ ΕΡΓΟΣΤΕΡΟΛΗΣ ΚΑΙ ΣΤΟΥΣ ΔΥΟ ΟΡΟΤΥΠΟΥΣ ΣΕ ΣΧΕΣΗ ΜΕ ΤΟΥΣ ΜΑΡΤΥΡΕΣ(Ρ<0.05). Η ΑΝΤΑΓΩΝΙΣΤΙΚΗ ΔΡΑΣΗ ΚΤΖ ΚΑΙ ΑΜΡ-Β, ΙΔΙΑΙΤΕΡΑ ΣΤΑ ΣΤΕΛΕΧΗ CA-B, ΣΥΖΗΤΑΤΑΙ ΣΕ ΣΧΕΣΗ ΜΕ ΤΗΝ ΕΠΙΛΟΓΗ ΚΑΤΑΛΛΗΛΗΣ ΣΥΝΔΥΑΣΜΕΝΗΣ ΧΗΜΕΙΟΘΕΡΑΠΕΙΑΣ. Η ΗΛΕΚΤΡΟΜΙΚΡΟΣΚΟΠΙΚΗ ΜΕΛΕΤΗ ΤΩΝ ΔΥΟ ΟΡΟΤΥΠΩΝ ΕΠΙΒΕΒΑΙΩΝΕΙ ΤΗΝ ΥΠΑΡΞΗ ΚΑΙ ΦΑΙΝΟΤΥΠΙΚΩΝΔΙΑΦΟΡΩΝ ΣΤΗΝ ΑΝΤΙΓΟΝΙΚΗ ΔΟΜΗ ΤΟΥΣ. Η ΚΛΙΝΙΚΗ ΚΑΙ ΕΡΓΑΣΤΗΡΙΑΚΗ ΣΗΜΑΣΙΑ ΤΩΝ ΕΥΡΗΜΑΤΩΝ ΑΥΤΩΝ ΣΥΖΗΤΑΤΑΙ ΣΕ ΑΝΤΙΣΤΟΙΧΑ ΚΕΦΑΛΑΙΑ

Novel Application of the Masson-Fontana Stain for Demonstrating Malassezia Species Melanin-Like Pigment Production In Vitro and in Clinical Specimens

Melanin-like pigment produced in vitro and in vivo by Malassezia yeasts has not been described before. Masson-Fontana staining confirmed accumulation of black pigment on the cell walls of l-dihydroxyphenylalaline (l-DOPA)-cultured Malassezia species. Black pigment was also observed in cells and hyphae from hyperpigmented patient lesions with culture-confirmed pityriasis versicolor and seborrheic dermatitis