Publications by authors named "Denis O"

216 Publications

Rapid COVID-19 antigenic tests: Usefulness of a modified method for diagnosis.

J Med Virol 2021 Sep 31;93(9):5655-5659. Epub 2021 May 31.

Department of Laboratory Medicine, Service of Medical Microbiology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium.

The current reliable recommended test for coronavirus disease 2019 (COVID-19) diagnosis is quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Rapid antigen test devices could be useful as they are less expensive, faster without the need of specialized laboratories to perform the test. We report the performances of two rapid immunochromatographic antigen testing devices compared with RT-qPCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal samples. We carried out a lateral-flow tests study on 401 nasopharyngeal swab samples from nonduplicated suspected COVID-19 subjects. An equal volume of universal transport medium tubes-containing samples (dilution ratio = 1:15) were added to the manufacturer's extraction buffer solution (dilution ratio = 1:2) and analyzed on BioSpeedia COVID19Speed-Antigen Test and on Abbott Panbio™ COVID-19 Ag Rapid Test, devices. Qualitative results were compared to those obtained by the RT-qPCR (Allplex™ SARS-CoV-2 Assay Seegene). Based on our data, the overall sensitivity for BioSpeedia and Panbio devices was estimated at 65.5% and 75.0%, respectively. The sensitivity was greater for cycle threshold values less than 25 achieving 90.4 and 96.8 for BioSpeedia and Panbio devices, respectively. A perfect specificity of 100.0% was observed for both devices.
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http://dx.doi.org/10.1002/jmv.27094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242554PMC
September 2021

Colistin resistance genes mcr-1 to mcr-5, including a case of triple occurrence (mcr-1, -3 and -5), in Escherichia coli isolates from faeces of healthy pigs, cattle and poultry in Belgium, 2012-2016.

Int J Antimicrob Agents 2021 Jun 25;57(6):106350. Epub 2021 Apr 25.

Veterinary Bacteriology, Sciensano, Ixelles, Belgium. Electronic address:

Colistin is a last-resort antimicrobial used to treat infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The emergence of colistin resistance, particularly linked to mobile genetic elements including the mcr genes, is a major threat to the management of MDR-GNB infections. The aim of this study was to assess the presence of mcr genes in a collection of 40 colistin-resistant commensal Escherichia coli isolated from healthy pigs, cattle and poultry in Belgium between 2012 and 2016. All isolates carried at least one mcr gene. The genes mcr-1 to -5 were observed in this collection. Different replicons associated with mcr genes were identified, including IncHI2/IncHI2A associated with mcr-1, IncX4 associated with mcr-1 and mcr-2, and ColE10 associated with mcr-4. While the occurrence of multiple mcr genes in a single isolate has rarely been reported elsewhere, a triple occurrence (mcr-1, -3 and -5) was found in this study. All isolates were MDR and carried between one and nine different replicons. Seventeen different sequence types were observed among the 40 E. coli isolates. In conclusion, this study revealed the presence of a reservoir of mobile colistin resistance genes (mcr-1 to -5) observed during at least 5 years (2012-2016) in the commensal gut flora of pigs, cattle and poultry in Belgium.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106350DOI Listing
June 2021

Unexpected Leishmania in a bone marrow aspirate.

Am J Hematol 2021 Mar 14. Epub 2021 Mar 14.

Department of Haematology, St. Mary's Hospital Campus of Imperial College London School of Medicine, London, UK.

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http://dx.doi.org/10.1002/ajh.26158DOI Listing
March 2021

First Investigative Study of Azole-Resistant in the Environment in Burkina Faso.

Int J Environ Res Public Health 2021 02 25;18(5). Epub 2021 Feb 25.

Department of Microbiology, LHUB-ULB, Université Libre de Bruxelles, Brussels, Rue Haute 322, 1000 Bruxelles, Belgium.

Azole-resistant (ARAF) strains have been reported on all continents, however, limited data exist on these strains in Africa, while several factors, mainly environmental ones, suggest their presence on this continent. This study aimed to assess the environmental prevalence of ARAF strains in Burkina Faso, a country situated in the West African region where data on ARAF is non-existent. In total, 120 environmental samples (soil) were collected and analyzed. Samples were screened for resistance using three azole-containing agar plates; one without azole antifungal (growth control) and two supplemented with either itraconazole (4 mg/L) or voriconazole (2 mg/L). The EUCAST susceptibility testing method was used to confirm the azole-resistant phenotype of sensu-stricto isolates. Mutations in the gene were determined by sequencing. Of the 120 samples, 51 positive samples showed growth of isolates on control medium. One ARAF (2%; 1/51) isolate was found amongst positive samples and harbored the F46Y/M172V/E427K mutations. No TR34/L98H or TR46/Y121F/T289A mutations were observed. Our study described the first isolate resistant to an azole antifungal in Burkina Faso.
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http://dx.doi.org/10.3390/ijerph18052250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956412PMC
February 2021

Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals.

J Virol Methods 2021 03 24;289:114060. Epub 2020 Dec 24.

Université catholique de Louvain, CHU UCL Namur, Department of Laboratory Medicine, Yvoir, Belgium.

Background: This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels.

Methods: Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020.

Results: A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso.

Conclusion: The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.
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http://dx.doi.org/10.1016/j.jviromet.2020.114060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834313PMC
March 2021

Multicenter study of automated systems for colistin susceptibility testing.

Eur J Clin Microbiol Infect Dis 2021 Mar 6;40(3):575-579. Epub 2020 Oct 6.

Department of Clinical Microbiology, National reference center for antibiotic-resistant Gram-negative bacilli, CHU UCL Namur, Yvoir, Belgium.

Purpose: Broth microdilution (BMD) stays as the reference testing method for determination of antimicrobial susceptibility testing (AST) to colistin and is considered essential for patient management and for monitoring of colistin resistance. This multicenter study aimed to evaluate the performance of automated systems for colistin AST among Enterobacterales as an alternative for BMD since the majority of laboratories use automated systems as first-line method.

Methods: Twenty colistin resistant (COL-R) including 10 MCR producers and 10 colistin-susceptible (COL-S) Enterobacterales isolates were blindly tested for colistin susceptibility with the routine automated AST systems used by 8 laboratories (3 with BD Phoenix, 3 with Vitek2 and 2 with MicroScan). Additionally, 3 reference strains (E. coli ATCC 25922, E. coli NCTC 13846, and one COL-R mcr-negative K. pneumoniae M/14750) were tested in triplicate by each laboratory.

Results And Conclusion: Results were compared with BMD performed at the reference laboratory. BD Phoenix and MicroScan automated AST systems provide accurate and reproducible categorical results for the testing of colistin in Enterobacterales. However, Vitek2 system showed poor performance for the detection of COL-R isolates especially those with MICs close to the susceptibility breakpoint (categorical agreement of 88% and precision categorical agreement of 81%).
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http://dx.doi.org/10.1007/s10096-020-04059-4DOI Listing
March 2021

Phylogeographical Analysis Reveals the Historic Origin, Emergence, and Evolutionary Dynamics of Methicillin-Resistant ST228.

Front Microbiol 2020 26;11:2063. Epub 2020 Aug 26.

Service of Hospital Preventive Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: Methicillin-resistant (MRSA) is a common healthcare-associated pathogen that remains a major public health concern. Sequence type 228 (ST228) was first described in Germany and spread to become a successful MRSA clone in several European countries. In 2000, ST228 emerged in Lausanne and has subsequently caused several large outbreaks. Here, we describe the evolutionary history of this clone and identify the genetic changes underlying its expansion in Switzerland.

Materials And Methods: We aimed to understand the phylogeographic and demographic dynamics of MRSA ST228/ST111 by sequencing 530 representative isolates of this clone that were collected from 14 European countries between 1997 and 2012.

Results: The phylogenetic analysis revealed distinct lineages of ST228 isolates associated with specific geographic origins. In contrast, isolates of ST111, which is a single locus variant of ST228 sharing the same type t041, formed a monophyletic cluster associated with multiple countries. The evidence points to a German origin of the sampled population, with the basal German lineage being characterized by type t001. The highly successful Swiss ST228 lineage diverged from this progenitor clone through the loss of the aminoglycoside-streptothricin resistance gene cluster and the gain of mupirocin resistance. This lineage was introduced first in Geneva and was subsequently introduced into Lausanne.

Conclusion: Our results reveal the radiation of distinct lineages of MRSA ST228 from a German progenitor, as the clone spread into different European countries. In Switzerland, ST228 was introduced first in Geneva and was subsequently introduced into Lausanne.
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http://dx.doi.org/10.3389/fmicb.2020.02063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479193PMC
August 2020

Recognition by Dendritic Cells Negatively Regulates Allergic Lung Inflammation through a TLR2/MyD88 Pathway.

Am J Respir Cell Mol Biol 2021 01;64(1):39-49

Service Immune Response and.

is an opportunistic fungal pathogen responsible for a spectrum of clinical manifestations. Dendritic cells recognize pathogen-associated molecular patterns of via two main receptor families, Toll-like receptors (TLRs) and C-type lectin receptors (CLR). Here, the importance of TLR and CLR signaling in the regulation of T-helper cell type 2 (Th2) responses was analyzed using a mouse model based on the transfer of bone marrow-derived dendritic cells (BMDCs) pulsed with conidia. BMDCs were generated from mice deficient in either MyD88 or MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1). Both the MyD88 and MALT1 signaling pathway in BMDCs contributed to the production of inflammatory cytokines induced by conidia. Mice sensitized with MyD88 BMDCs pulsed with conidia showed an exacerbated allergic inflammation, with stronger eosinophil recruitment in the BAL and higher Th2 cytokine production compared with mice sensitized with wild-type or MALT1 BMDCs. This exacerbation was not observed when MyD88 BMDCs were pulsed with , a nonpathogenic mold. A lack of TLR2 signaling recapitulated the exacerbation of the Th2 response observed in the absence of MyD88 signaling, whereas TLR2 agonist dampened the response induced with and conidia. IL-10 production by BMDCs in response to was dependent on the expression of TLR2 and MyD88. IL-10 BMDCs exacerbated, whereas MyD88 BMDCs supplemented with exogenous IL-10 decreased the allergic pulmonary inflammation. These results indicate that TLR2/MyD88-specific recognition of PAMPs from conidia can upregulate IL-10 production and downregulate lung eosinophilia and the development of a Th2 response.
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http://dx.doi.org/10.1165/rcmb.2020-0083OCDOI Listing
January 2021

Progressive Control of Streptococcus agalactiae-Induced Innate Inflammatory Response Is Associated with Time Course Expression of MicroRNA-223 by Neutrophils.

Infect Immun 2020 11 16;88(12). Epub 2020 Nov 16.

Inflammation Unit, Laboratory of Pediatric Research, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium

Group B streptococcus (GBS) is a human-pathogenic bacterium inducing a strong inflammatory response that may be detrimental for host tissues if not finely regulated. The inflammatory response can be modulated by different molecular mechanisms, among which growing evidence points toward the crucial role of microRNAs (miRNAs). Regarding innate inflammatory response, studies have reported that miR-223 is essential for the control of granulocyte proliferation and activation. Moreover, a number of investigations on miRNA expression profiling performed in various inflammatory settings have revealed that miR-223 is among the top differentially expressed miRNAs. Yet the dynamic pattern of expression of miR-223 with respect to the evolution of the inflammatory process, especially in microbial infection, remains elusive. In this study, we analyzed the kinetic expression of miR-223 in an inflammatory model of GBS-induced murine pneumonia and looked for correlates with inflammatory markers, including innate cell infiltrates. We found that miR-223 expression is rapidly induced at very early time points (3 to 6 h postinfection [p.i.]) mainly by lung-infiltrating neutrophils. Interestingly, the level of miR-223 accumulating in the lungs remains higher at later stages of infection (24 h and 48 h p.i.), and this correlates with reduced expression of primary inflammatory cytokines and chemokines and with a shift in infiltrating monocyte and macrophage subtypes toward a regulatory phenotype. Transient inhibition of miR-223 by an antagomir resulted in significant increase of CXCL2 expression and partial enhancement of infiltrating neutrophils in GBS-infected lung tissues. This suggests the potential contribution of miR-223 to the resolution phase of GBS-induced acute inflammation.
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http://dx.doi.org/10.1128/IAI.00563-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671897PMC
November 2020

Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial.

Clin Microbiol Infect 2021 Mar 10;27(3):398-405. Epub 2020 Sep 10.

Department of Nephrology, Universitair Ziekenhuis Antwerpen, Universiteit Antwerpen, Antwerp, Belgium.

Objectives: Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB.

Methods: We performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months.

Results: One hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50-1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20-41, versus 6, interquartile range 0-15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003).

Conclusions: Applying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms.
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http://dx.doi.org/10.1016/j.cmi.2020.09.005DOI Listing
March 2021

Cross-border spread of - and -positive : a European collaborative analysis of whole genome sequencing and epidemiological data, 2014 to 2019.

Euro Surveill 2020 05;25(20)

European Centre for Disease Prevention and Control, Stockholm, Sweden.

Analysis of sequencing data for 143 - and -positive isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.20.2000627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262493PMC
May 2020

Multidrug resistance of the extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolated in Tizi-Ouzou (Algeria).

Cell Mol Biol (Noisy-le-grand) 2019 Dec 31;65(8):11-17. Epub 2019 Dec 31.

Laboratoire De Biochimie Appliquée et biotechnologie (LABAB), Université MOULOUD Mammeri, Tizi-Ouzou, 15000, Algérie.

The emergence and spread of multidrug-resistant bacteria is a major public health concern. This study sought to investigate the phenotypic and genotypic characteristics of clinical isolates of ESBL-producing Klebsiella pneumoniae, at University Hospital of Tizi-Ouzou.  Antibiotic susceptibility testing of the strains was carried out by the disc diffusion method, the ESBL production was screening by the Double Disc Synergy Test and  confirmed by the Phenotypic Confirmatory Disc Diffusion Test. Genomic DNA was extracted using the  Qiagen DNeasy Blood & Tissue Kit  mini kit (Qiagen) according to the manufacturer's instructions.PCR targeting the genes  blaCTX-M, blaTEM, blaSHV, blaVEB, blaGES, blaPER, blaBEL, blaVIM, blaIMP, blaKPC, blaNDM and blaOXA48 was performed. A CTX-M PCR-based grouping method was carried out using primers specific to the groups 1, 2 and 9. Conjugative transfer of plasmids was carried out using sodium azide-resistant recipient strain Escherichia coli K12. The phylogenetic relationship was determined by ERIC-PCR. All strains of K. pneumoniae tested shared ESBL producer's genes belonging to the CTX-M group 1. These strains showed a high level of resistance to ß-lactams, aminoglycosides, fluoroquinolones and trimethoprim/ sulfamethoxazole. Resistance to fosfomycin was also detected in one strain of K. pneumoniae. Only one carbapenem-resistant strain was isolated. Phylogenetic analysis showed 49 different genetic profiles of K. pneumoniae strains, showing the absence of clonality. This study revealed a high prevalence of ESBL belonging to the CTX-M group 1 in K. pneumoniae tested. The emergence of resistance to carbapenem and fosfomycin, could seriously limits the therapeutic choices options.
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December 2019

The protective effect of rural life on mite sensitization disappears among urban migrants in the South of Vietnam.

World Allergy Organ J 2019 Dec 26;12(12):100085. Epub 2019 Nov 26.

Clinic of Immuno-allergology, CHU Brugmann, Université Libre de Bruxelles (ULB), 4 Place A Van Gehuchten, B -1020, Brussels, Belgium.

Background: Rapid urbanization combined with rural migration to urban areas in southern Vietnam could be risk factors for allergen sensitization, contributing to chronic respiratory diseases (CRD). We aimed to evaluate the prevalence of mite sensitization and its relation to house dust characteristics among rural and urban native and migrating populations with CRD.

Methods: Rural (n = 19) and urban (n = 46) dwellings were defined on the basis of a home typology. Controls were western Belgian houses (n = 14). Besides the house characteristics, both endotoxin and mite allergens were measured in the settled dusts. The sensitization to mite allergens was defined by positive skin prick test (SPT) and concentration of specific IgE (sIgE)≥ 0.7 U/mL. The prevalence of mite sensitization was evaluated among 610 patients with CRD and compared according to both their home types and places of birth and residences.

Results: The concentration of endotoxin (but not mite allergen) was higher in rural compared to urban dusts (440 (95%CI: 314-566) versus 170 (95%CI: 115-226) EU/mg; p < 0.0001). The prevalence of positive sIgE to Der p1 and Der p2 was significantly lower in rural (9% and 5%) compared to urban (15% and 9%) population, consistent with the positive SPT to mite (14% and 21%, respectively). Among the urban migrants, the risk of mite sensitization (SPT) was higher compared to the rural natives (OR: 1.79 (1.02-3.15), p < 0.05) and not different to the urban ones (OR: 1.35 (0.82-2.23) p NS).

Conclusion: In Vietnam, associated with higher endotoxin (but not allergen) dust concentrations, the risk of mite sensitization was lower in rural compared to the native urban population, but this protective effect could disappear among rural to urban migrants.
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http://dx.doi.org/10.1016/j.waojou.2019.100085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889047PMC
December 2019

Prevalence of multidrug-resistant organisms in nursing homes in Belgium in 2015.

PLoS One 2019 28;14(3):e0214327. Epub 2019 Mar 28.

National Reference Centre for antibiotic resistant Gram-negative bacilli, Laboratory of Clinical Microbiology, Centre hospitalier universitaire de Namur, Université catholique de Louvain, Yvoir, Belgium.

Objectives: Following two studies conducted in 2005 and 2011, a third prevalence survey of multidrug-resistant microorganisms (MDRO) was organised in Belgian nursing homes (NHs) using a similar methodology. The aim was to measure the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase producing Enterobacteriaceae (ESBLE) and carbapenemase-producing Enterobacteriaceae (CPE) in NH residents. Risk factors for MDRO carriage were also explored.

Methods: Up to 51 randomly selected residents per NH were screened for MDRO carriage by trained local nurses between June and October 2015. Rectal swabs were cultured for ESBLE, CPE and VRE, while pooled samples of nose, throat and perineum and chronic wound swabs were obtained for culture of MRSA. Antimicrobial susceptibility testing, molecular detection of resistance genes and strain genotyping were performed. Significant risk factors for MDRO colonization MDRO was determined by univariate and multivariable analysis.

Results: Overall, 1447 residents from 29 NHs were enrolled. The mean weighted prevalence of ESBLE and MRSA colonization was 11.3% and 9.0%, respectively. Co-colonization occurred in 1.8% of the residents. VRE and CPE carriage were identified in only one resident each. Impaired mobility and recent treatment with fluoroquinolones or with combinations of sulphonamides and trimethoprim were identified as risk factors for ESBLE carriage, while for MRSA these were previous MRSA carriage/infection, a stay in several different hospital wards during the past year, and a recent treatment with nitrofuran derivatives. Current antacid use was a predictor for both ESBL and MRSA carriage.

Conclusions: In line with the evolution of MRSA and ESBL colonization/infection in hospitals, a decline in MRSA carriage and an increase in ESBLE prevalence was seen in Belgian NHs between 2005 and 2015. These results show that a systemic approach, including surveillance and enhancement of infection control and antimicrobial stewardship programs is needed in both acute and chronic care facilities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214327PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438666PMC
December 2019

Helminth-induced IL-4 expands bystander memory CD8 T cells for early control of viral infection.

Nat Commun 2018 10 30;9(1):4516. Epub 2018 Oct 30.

Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine - FARAH, University of Liège, Avenue de Cureghem 10, 4000, Liège, Belgium.

Infection with parasitic helminths can imprint the immune system to modulate bystander inflammatory processes. Bystander or virtual memory CD8 T cells (T) are non-conventional T cells displaying memory properties that can be generated through responsiveness to interleukin (IL)-4. However, it is not clear if helminth-induced type 2 immunity functionally affects the T compartment. Here, we show that helminths expand CD44CD62LCXCR3CD49d T cells through direct IL-4 signaling in CD8 T cells. Importantly, helminth-mediated conditioning of T cells provided enhanced control of acute respiratory infection with the murid gammaherpesvirus 4 (MuHV-4). This enhanced control of MuHV-4 infection could further be explained by an increase in antigen-specific CD8 T cell effector responses in the lung and was directly dependent on IL-4 signaling. These results demonstrate that IL-4 during helminth infection can non-specifically condition CD8 T cells, leading to a subsequently raised antigen-specific CD8 T cell activation that enhances control of viral infection.
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http://dx.doi.org/10.1038/s41467-018-06978-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207712PMC
October 2018

Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing.

Nephrol Dial Transplant 2019 05;34(5):878-885

Department of Microbiology, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Background: Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions.

Methods: We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012-June 2015). Whole-genome sequencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected.

Results: We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5-33) and 18 (5-30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences were apparent for 86 other bacterial and host variables.

Conclusions: Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.
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http://dx.doi.org/10.1093/ndt/gfy292DOI Listing
May 2019

Allergic Asthma Favors Growth in the Lungs of Infected Mice.

Front Immunol 2018 10;9:1856. Epub 2018 Aug 10.

Unité de Recherche en Biologie des Microorganismes, Laboratoire d'Immunologie et de Microbiologie, NAmur Research Institute for Life Sciences (NARILIS), Université de Namur, Namur, Belgium.

Allergic asthma is a chronic Th2 inflammatory disease of the lower airways affecting a growing number of people worldwide. The impact of infections and microbiota composition on allergic asthma has been investigated frequently. Until now, however, there have been few attempts to investigate the impact of asthma on the control of infectious microorganisms and the underlying mechanisms. In this work, we characterize the consequences of allergic asthma on intranasal (i.n.) infection by bacteria in mice. We observed that i.n. sensitization with extracts of the house dust mite or the mold () significantly increased the number of , and in the lungs of infected mice. Microscopic analysis showed dense aggregates of infected cells composed mainly of alveolar macrophages (CD11c F4/80 MHCII) surrounded by neutrophils (Ly-6G). Asthma-induced susceptibility appears to be dependent on CD4 T cells, the IL-4/STAT6 signaling pathway and IL-10, and is maintained in IL-12- and IFN-γR-deficient mice. The effects of the sensitization protocol were also tested on and pulmonary infections. Surprisingly, we observed that sensitization strongly increases the survival of infected mice by a T cell and STAT6 independent signaling pathway. In contrast, the course of infection is not affected in the lungs of sensitized mice. Our work demonstrates that the impact of the same allergic sensitization protocol can be neutral, negative, or positive with regard to the resistance of mice to bacterial infection, depending on the bacterial species.
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http://dx.doi.org/10.3389/fimmu.2018.01856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095999PMC
September 2019

European external quality assessments for identification, molecular typing and characterization of Staphylococcus aureus.

J Antimicrob Chemother 2018 10;73(10):2662-2666

Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, 103 Grande Rue de la Croix Rousse, Lyon, France.

Objectives: We present the results of two European external quality assessments (EQAs) conducted in 2014 and 2016 under the auspices of the Study Group on Staphylococci and Staphylococcal Infections of ESCMID. The objective was to assess the performance of participating centres in characterizing Staphylococcus aureus using their standard in-house phenotypic and genotypic protocols.

Methods: A total of 11 well-characterized blindly coded S. aureus (n = 9), Staphylococcus argenteus (n = 1) and Staphylococcus capitis (n = 1) strains were distributed to participants for analysis. Species identification, MIC determination, antimicrobial susceptibility testing, antimicrobial resistance and toxin gene detection and molecular typing including spa typing, SCCmec typing and MLST were performed.

Results: Thirteen laboratories from 12 European countries participated in one EQA or both EQAs. Despite considerable diversity in the methods employed, good concordance (90%-100%) with expected results was obtained. Discrepancies were observed for: (i) identification of the S. argenteus strain; (ii) phenotypic detection of low-level resistance to oxacillin in the mecC-positive strain; (iii) phenotypic detection of the inducible MLSB strain; and (iv) WGS-based detection of some resistance and toxin genes.

Conclusions: Overall, good concordance (90%-100%) with expected results was observed. In some instances, the accurate detection of resistance and toxin genes from WGS data proved problematic, highlighting the need for validated and internationally agreed-on bioinformatics pipelines before such techniques are implemented routinely by microbiology laboratories. We strongly recommend all national reference laboratories and laboratories acting as referral centres to participate in such EQA initiatives.
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http://dx.doi.org/10.1093/jac/dky260DOI Listing
October 2018

An Outpatient Clinic as a Potential Site of Transmission for an Outbreak of New Delhi Metallo-β-Lactamase-producing Klebsiella pneumoniae Sequence Type 716: A Study Using Whole-genome Sequencing.

Clin Infect Dis 2019 03;68(6):993-1000

Laboratoire de Microbiologie, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels.

Background: The incidence of nosocomial infections due to carbapenem-resistant Klebsiella pneumoniae is increasing worldwide. Whole-genome sequencing (WGS) can help elucidate the transmission route of nosocomial pathogens.

Methods: We combined WGS and epidemiological data to analyze an outbreak of New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae that occurred in 2 Belgian hospitals situated about 50 miles apart. We characterized 74 NDM-producing K. pneumoniae isolates (9 from hospital A, 24 from hospital B, and 41 contemporary isolates from 15 other Belgian hospitals) using pulsed-field gel electrophoresis and WGS.

Results: A K. pneumoniae sequence type 716 clone was identified as being responsible for the outbreak with all 9 strains from hospital A and 20 of 24 from hospital B sharing a unique pulsotype and being clustered together at WGS (compared with 1 of 41 isolates from other Belgian hospitals). We identified the outpatient clinic of hospital B as the probable bridging site between the hospitals after combining epidemiological, phylogenetic, and resistome data. We also identified the patient who probably caused the transmission. In fact, all but 1 strain from hospital A carried a Tn1331-like transposon, whereas none of the hospital B isolates did. The patient from hospital A who did not have the Tn1331-like transposon was treated at the outpatient clinic of hospital B on the same day as the first NDM-producing K. pneumoniae-positive patient from hospital B.

Conclusions: The results from our WGS-guided investigation highlight the importance of implementing adequate infection control measures in outpatient settings, especially when healthcare delivery moves from acute care facilities to outpatient clinics.
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http://dx.doi.org/10.1093/cid/ciy581DOI Listing
March 2019

Relationship between mold exposure, specific IgE sensitization, and clinical asthma: A case-control study.

Ann Allergy Asthma Immunol 2018 09 23;121(3):333-339. Epub 2018 Jun 23.

Clinic of Immunology and Allergology, CHU Brugmann (Université Libre de Bruxelles-ULB), Brussels, Belgium.

Background: Most of the findings related to the noxious effect of mold sensitization on asthma come from investigations based on Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus. However, species such as Penicillium spp, Cladosporium sphaerospermum, Cladosporium cladosporioides, or Aspergillus versicolor display a more pronounced indoor tropism, and their potential harmful respiratory effects cannot be neglected.

Objective: The goal of this work was to relate mold sensitizations with asthma severity and with the level of indoor mold contamination among mold-sensitized patients with asthma and nonsensitized patients with asthma.

Methods: A case-control study was conducted and several asthma severity markers were compared between patients with asthma with and without mold sensitization. Indoor contamination of patients' dwellings was also investigated.

Results: Our findings confirmed the association between sensitization to A fumigatus and severity for patients with asthma in contrast with sensitization to other species. Indoor mold contamination was detected in approximately 90% of dwellings. Overall mold exposure was not associated with asthma severity. However, regardless of the sensitization, exposure to A fumigatus and Penicillium spp in dust was linked to an increased risk of severe asthma.

Conclusion: The harmful nature of mold sensitization and mold exposure for patients with asthma was not confirmed in this study. However, sensitization to A fumigatus was associated with an increased risk for severe asthma. A better investigation of the properties of Penicillium spp is recommended because its exposure was found to be associated with a more pronounced impairment of lung function.
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http://dx.doi.org/10.1016/j.anai.2018.06.016DOI Listing
September 2018

Emergence of livestock-associated MRSA isolated from cystic fibrosis patients: Result of a Belgian national survey.

J Cyst Fibros 2019 01 24;18(1):86-93. Epub 2018 May 24.

National Reference centre MRSA-Staphylococcus, Microbiology Department, Erasme University Hospital, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.

Background: This study aims to determine the prevalence and characteristics of Staphylococcus aureus in Belgian cystic fibrosis (CF) patients.

Methods: Non-duplicate respiratory samples from 510 CF-patients (2012-2013) were examined. One isolate per patient was analysed unless different phenotypes were recovered. Isolates were investigated for mecA/mecC, toxins presence, spa-typing, MLST and SCCmec-typing. Potential livestock-associated (LA) isolates were examined for their immune-evasion-cluster (IEC) genes.

Results: S. aureus (n = 380), including 41 small-colony variants (SCVs), were isolated from 66.7% patients. The prevalence of methicillin-resistant S. aureus (MRSA) colonization was 4.9%. Two MRSA isolates carried toxic shock syndrome toxin 1 (TSST-1). Most MRSA (65%) belonged to two nosocomial epidemic clones (CC5, CC8) widespread in Belgium. Methicillin susceptible S. aureus (MSSA) showed great genetic diversity. Five of 33 isolates belonging to potential LA-lineages were IEC negative, including three methicillin-resistant isolates, suggesting an animal origin.

Conclusions: The MRSA-prevalence in Belgian CF-patients remained constant (2001-2013), but SCV-prevalence increased. Most MRSA belonged to health-care-associated clones. Three patients carrying LA-MRSA were found, requiring further investigation to determine the risk factors for LA-MRSA acquisition.
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http://dx.doi.org/10.1016/j.jcf.2018.04.008DOI Listing
January 2019

Genetic Diversity among Staphylococcus aureus Isolates Showing Oxacillin and/or Cefoxitin Resistance Not Linked to the Presence of Genes.

Antimicrob Agents Chemother 2018 07 26;62(7). Epub 2018 Jun 26.

National Reference Centre for Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Methicillin-resistant isolates lacking genes ( = 32), collected from Belgian hospitals, were characterized for their β-lactamase production and the presence of mutations in genes, the promoter, and genes involved in penicillin-binding protein 4 overproduction ( and ). Twelve isolates were β-lactamase hyperproducers (BHPs), while 12 non-BHP isolates might produce an incomplete GdpP protein. Most isolates showed nucleotide missense mutations in genes. A few isolates also showed mutations in the promoter.
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http://dx.doi.org/10.1128/AAC.00091-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021684PMC
July 2018

STAT6 Mediates Footpad Immunopathology in the Absence of IL-12p40 Following Infection of Susceptible BALB/c Mice With .

Front Immunol 2018 14;9:503. Epub 2018 Mar 14.

Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

() parasites are intracellular parasites belong to the family and are the causative agent of cutaneous leishmaniasis. This disease affects approximately 1.5 million per year worldwide and there is currently no prophylactic vaccine available. is transmitted by the bite of an infected sandfly and has been considered for decades now as a mouse model of choice to identify the factors implicated in T helper (Th)1 and Th2 polarization due to the natural resistance and susceptibility to infection of C57BL/6 and BALB/c mice, respectively. In this study, we refine the role of IL-12p40 cytokine, which is implicated the development of a protective Th1 response, and STAT6, a transcription factor involved in the signaling detrimental interleukin (IL)-4 and IL-13 associated Th2 cytokines during infection in the BALB/c model. In the absence of STAT6 and IL-12p40 signaling, double knockout (DKO) susceptible BALB/c mice displayed reduced footpad swelling and ulcerative lesion compared to IL-12p40 mice upon infection. Hence, they expressed slower upregulation of keratinocyte markers implicated in the inhibition of wound healing, such as keratin 6a (Krt6a) and Krt16. This coincides with the presence of neutrophils displaying an altered phenotype characterized by a lower expression of surface markers Ly6C, CD11b, and Ly6G. These neutrophils exhibited very lower levels of apoptosis similarly to neutrophils present in resistant STAT6 mice. Interestingly, the reduced footpad swelling in DKO mice is associated with a high footpad parasite level similar to susceptible IL-12p40 mice. In conclusion, this study demonstrate that in the absence of both STAT6 and IL-12p40 signaling, -infected mice display smaller and less ulcerated lesions, which does, however, not correlate with reduced parasite load. In addition, the presence of neutrophils with an altered phenotype is associated with reduced apoptosis and delayed immunopathologies, demonstrating the detrimental role of STAT6 in infected susceptible BALB/c mice.
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http://dx.doi.org/10.3389/fimmu.2018.00503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861353PMC
May 2019

CC398 Staphylococcus aureus subpopulations in Belgian patients.

Eur J Clin Microbiol Infect Dis 2018 May 15;37(5):911-916. Epub 2018 Feb 15.

National Reference Centre-Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium.

Studies based on genome-wide single nucleotide polymorphisms (SNPs) supported the existence of two subpopulations in clonal complex (CC) 398 Staphylococcus aureus: an ancestral human-adapted clade (HC) and an animal-associated clade (AC). In this study, we have investigated the occurrence of genetic markers that allow discrimination of these subpopulations among CC398 isolates collected during 2014 to 2016 from human patients in Belgium. A collection of isolates was investigated by means of spa-typing and 16S-mecA-nuc PCR. CC398 isolates were classified as belonging to the human or the animal clade by using a canonical SNPs PCR and further studied by antimicrobial susceptibility and the presence of toxins, immune evasion cluster (IEC), and resistance genes. A total of 124 (7.8%) human isolates belonged to CC398. They were grouped into HC (n = 58) or AC (n = 66). The genes erm(T), pvl, chp, and scn were predominantly found in HC-CC398, while AC-CC398 isolates carried more frequently than the mecA, erm(C), tet(K), tet(M), and tet(L) genes. Different combinations of gene profiles were observed according to the clade. CC398 isolates from Belgian patients belonged to different subpopulations including typical HC and AC-isolates. Few HC-strains with mecA and AC-isolates harboring IEC were found. CC398 isolates from Belgian patients belonged to different subpopulations including typical HC and AC-isolates, as well as new emerging subpopulations that underline the ability of this lineage to acquire resistance and virulence genes. Further research is needed to evaluate the emergence of these subpopulations in the clinical setting.
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http://dx.doi.org/10.1007/s10096-018-3205-yDOI Listing
May 2018

Mutations at the Ribosomal S10 Gene in Clinical Strains of Staphylococcus aureus with Reduced Susceptibility to Tigecycline.

Antimicrob Agents Chemother 2018 01 21;62(1). Epub 2017 Dec 21.

National Reference Centre-Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

Mutations on the tip of the extended loop of the ribosomal S10 protein have been associated to tigecycline (TGC) resistance in passaged mutants of different bacteria species. This study described the first two clinical TGC-resistant isolates with these mutations. One strain (TGC MIC = 2 mg/liter) had a 12-nucleotide deletion affecting residues 56 to 59 (HKYK) of the S10 protein. The second strain (TGC MIC = 1 mg/liter) had amino acid substitutions (K57M and Y58F) previously described in passaged mutants.
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http://dx.doi.org/10.1128/AAC.01852-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740382PMC
January 2018

Comparison of Different Phenotypic Approaches To Screen and Detect -Harboring Methicillin-Resistant Staphylococcus aureus.

J Clin Microbiol 2018 01 26;56(1). Epub 2017 Dec 26.

Institute of Medical Microbiology, University Hospital Münster, Münster, Germany

Similar to , confers resistance against beta-lactams, leading to the phenotype of methicillin-resistant (MRSA). However, -harboring MRSA strains pose special difficulties in their detection. The aim of this study was to assess and compare different phenotypic systems for screening, identification, and susceptibility testing of -positive MRSA isolates. A well-characterized collection of -positive isolates ( = 111) was used for evaluation. Routinely used approaches were studied to determine their suitability to correctly identify -harboring MRSA, including three (semi)automated antimicrobial susceptibility testing (AST) systems and five selective chromogenic agar plates. Additionally, a cefoxitin disk diffusion test and an oxacillin broth microdilution assay were examined. All -harboring MRSA isolates were able to grow on all chromogenic MRSA screening plates tested. Detection of these isolates in AST systems based on cefoxitin and/or oxacillin testing yielded overall positive agreements with the genotype of 97.3% (MicroScan WalkAway; Siemens), 91.9% (Vitek 2; bioMérieux), and 64.9% (Phoenix, BD). The phenotypic resistance pattern most frequently observed by AST devices was "cefoxitin resistance/oxacillin susceptibility," ranging from 54.1% (Phoenix) and 83.8% (Vitek 2) to 92.8% (WalkAway). The cefoxitin disk diffusion and oxacillin broth microdilution assays categorized 100% and 61.3% of isolates to be MRSA, respectively. The chromogenic media tested confirmed their suitability to reliably screen for -harboring MRSA. The AST systems showed false-negative results with varying numbers, misidentifying -harboring MRSA as methicillin-susceptible This study underlines cefoxitin's status as the superior surrogate -positive MRSA marker.
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http://dx.doi.org/10.1128/JCM.00826-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744205PMC
January 2018

Prospective evaluation of a high multiplexing real-time polymerase chain reaction array for the rapid identification and characterization of bacteria causative of nosocomial pneumonia from clinical specimens: a proof-of-concept study.

Eur J Clin Microbiol Infect Dis 2018 Jan 27;37(1):109-116. Epub 2017 Sep 27.

Microbiology Laboratory, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

The purpose of this study was evaluation of the VAPChip assay based on the "Rapid-Array-PCR-technology" which targets 13 respiratory pathogens and 24 β-lactam resistance genes directly on respiratory clinical specimens. The first step included analysis of 45 respiratory specimens in order to calibrate and determine the threshold for target genes. The second prospective step involved 85 respiratory samples from patients suspected of nosocomial pneumonia collected in two academic hospitals over an 8-month period. Results of the VAPChip assay were compared to routine methods. The first step showed a large proportion of positive signals for H. influenzae and/or S. pneumoniae. For identification, discrepancies were observed in seven samples. Thresholds were adapted and two probes were re-designed to create a new version of the cartridge. In the second phase, sensitivity and specificity of the VAPchip for bacterial identification were 72.9% and 99.1%, respectively. Seventy (82%) pathogens were correctly identified by both methods. Nine pathogens detected by the VAPChip were culture negative and 26 pathogens identified by culture were VAPChip negative. For resistance mechanisms, 11 probes were positive without identification of pathogens with an antimicrobial-susceptibility testing compatible by culture. However, the patient's recent microbiological history was able to explain most of these positive signals. The VAPChip assay simultaneously detects different pathogens and resistance mechanisms directly from clinical samples. This system seems very promising but the extraction process needs to be automated for routine implementation. This kind of rapid point-of-care automated platform permitting a syndromic approach will be the future challenge in the management of infectious diseases.
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http://dx.doi.org/10.1007/s10096-017-3108-3DOI Listing
January 2018

Multicentre evaluation of the BYG Carba v2.0 test, a simplified electrochemical assay for the rapid laboratory detection of carbapenemase-producing Enterobacteriaceae.

Sci Rep 2017 08 30;7(1):9937. Epub 2017 Aug 30.

Laboratory of clinical microbiology, National reference center for monitoring antimicrobial resistance in Gram-negative bacteria, CHU UCL Namur, Yvoir, Belgium.

Rapid detection of carbapenemase-producing Enterobacteriaceae (CPE) represents a major challenge for microbiology laboratories. We evaluated the BYG Carba v2.0 using a simplified protocol, which detects CPE in less than 30 minutes. This new procedure reduces the hands-on-time from 5 to one minute and only requires a limited amount of material (one to three colonies) thereby preventing the need for subculturing bacterial isolates to reach a larger amount of pure biomass. This multicentre study involved four European reference laboratories. For the 1181 isolates tested across four centres, BYG Carba v2.0 yielded overall sensitivity and specificity of 96.3% (CI95: 94.5-97.5) and 99.7% (CI95: 98.6-100) respectively. Considering only the 670 consecutive isolates tested prospectively, the BYG Carba v2.0 displayed overall positive and negative predictive values of 99.7% (CI95: 95.4-98.9) and 97.5% (CI95: 94.9-98.8). Regarding time to positivity, 85% of CPE detected were positive within ten minutes. The BYG Carba v2.0 is a new highly simplified, rapid and accurate electrochemical assay discriminating between CPE and non-CPE in less than 30 min. The real-time quantified signal allows objective and traceable interpretation of the results.
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http://dx.doi.org/10.1038/s41598-017-09820-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577128PMC
August 2017

Bacteria from Animals as a Pool of Antimicrobial Resistance Genes.

Antibiotics (Basel) 2017 Jun 6;6(2). Epub 2017 Jun 6.

National Reference Centre-Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.

Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (, , (), , , and ) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.
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http://dx.doi.org/10.3390/antibiotics6020012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485445PMC
June 2017
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