Uniform distribution of three Candida albicans microsatellite markers in two French ICU populations supports a lack of nosocomial cross-contamination

BACKGROUND: The nosocomial acquisition of Candida albicans is a growing concern in intensive care units (ICUs) and understanding the route of contamination is relevant for infection control guidelines. METHODS: To analyze whether there is a specific ecology for any given hospital, we genotyped C. albicans isolates of the ICU of Versailles hospital (Hospital A) and compared the results with those previously obtained in another ICU in Henri Mondor hospital (Hospital B) using three polymorphic microsatellite markers (PMM). RESULTS: Among 36 patients with at least one positive culture for C. albicans, 26 had a specific multilocus genotype, two shared a common multilocus genotype, and 8 had the most common multilocus genotype found in the general population. The time interval between periods of hospitalization between patients with common genotypes differed by 13 to 78 days, thus supporting a lack of direct contamination. To confirm this hypothesis, the multilocus genotypic distributions of the three PMM were compared between the two hospitals. No statistically significant difference was observed. Multiple correspondences analysis did not indicate the association of a multilocus genotypic distribution with any given hospital. CONCLUSION: The present epidemiological study supports the conclusions that each patient harbours his/her own isolate, and that nosocomial transmission is not common in any given ICU. This study also supports the usefulness and practicability of PMM for studying the epidemiology of C. albicans

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

Efficacy and Pharmacokinetics Evaluation of a Single Oral Dose of Afoxolaner against Sarcoptes scabiei in the Porcine Scabies Model for Human Infestation

Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and treated either with 2.5 mg/kg single dose oral AFX (n = 4), 0.2 mg/kg two-doses 8 days apart oral ivermectin (IVM, n = 4), or no treatment against scabies (n = 4). Response to treatment was assessed by reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetic profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 post-treatment and remained unchanged until the study-end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at study-end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1±2.4 and 1.1±0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2±16.9 and 2.7±0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed a remarkably long MRT in plasma and notably in the skin

Pruritus scores (mean ±SD) over time from scabies-infection induction throughout the post-treatment period for MOX- and IVM-treated groups and control pigs.

<p>W, week; D, day.</p

MOX and IVM pharmacokinetic parameters of scabies-infected pig plasma and skin.

<p>MOX and IVM pharmacokinetic parameters of scabies-infected pig plasma and skin.</p

ELISA-assessed serological responses (expressed as mean %OD ± SD) after <i>S</i>. <i>scabiei</i> infection throughout the post-treatment period of the MOX- and IVM-treated groups and control pigs.

<p>W, week; D, day.</p

Skin MOX and IVM concentrations (mean ± SD, ng/g) after oral intake in scabies-infected pigs.

<p>Concentrations measured on D2, 7, 9, 14, 22, 36, and 47 post-treatment are depicted. Predicted parts of the curves are indicated as a dashed line. W, week; D, day.</p

Diagram of the study design showing the 3 experimental phases: housing and acclimation phase, experimental phases 1 and 2.

<p>DXM, dexamethasone; D, day.</p

Primary outcome of MOX, IVM or no treatment of experimental scabies in pigs.

<p>Primary outcome of MOX, IVM or no treatment of experimental scabies in pigs.</p

Spectrum of Pulmonary Aspergillosis in Hyper-IgE Syndrome with Autosomal-Dominant STAT3 Deficiency

International audienceBackground: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging.Objective: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort.Methods: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized.Results: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse.Conclusions: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery