Web-based prediction of antimicrobial resistance in enterococcal clinical isolates by whole-genome sequencing

Penven, Malo; Zouari, Asma; Nogues, Sophie; Collet, Anaïs; Lecourt, Maxime; Birer, Alain; Guérin, François; Auger, Gabriel; Cattoir, Vincent

doi:10.1007/s10096-022-04527-z

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…We identified a correlation between phenotypic linezolid susceptibility and a corresponding genotype, as others have previously described [31]: the number of mutated 23S rRNA copies was inversely correlated with the antibiotic disc diffusion zone diameter. This finding is in line with earlier reports on the level of resistance to linezolid that correlated with the proportion of mutated 23S rRNA copies (gene dosage effect) [32,33].…”

Section: Discussionsupporting

confidence: 72%

Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen

et al. 2023

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Linezolid is used as first-line treatment of infections caused by vancomycin-resistant Enterococcus faecium . However, resistance to linezolid is increasingly detected. The aim of the present study was to elucidate the causes and mechanisms for the increase in linezolid-resistant E. faecium at Copenhagen University Hospital – Rigshospitalet. We therefore combined patient information on linezolid treatment with whole-genome sequencing data for vancomycin- or linezolid-resistant E. faecium isolates that had been systematically collected since 2014 (n=458). Whole-genome sequencing was performed for multilocus sequence typing (MLST), identification of linezolid resistance-conferring genes/mutations and determination of phylogenetically closely related strains. The collection of E. faecium isolates belonged to prevalent vancomycin-resistant MLST types. Among these, we identified clusters of closely related linezolid-resistant strains compatible with nosocomial transmission. We also identified linezolid-resistant enterococcus isolates not genetically closely related to other isolates compatible with de novo generation of linezolid resistance. Patients with the latter isolates were significantly more frequently exposed to linezolid treatment than patients with related linezolid-resistant enterococcus isolates. We also identified six patients who initially carried a vancomycin-resistant, linezolid-sensitive enterococcus, but from whom vancomycin-resistant, linezolid-resistant enterococci (LVRE) closely related to their initial isolate were recovered after linezolid treatment. Our data illustrate that linezolid resistance may develop in the individual patient subsequent to linezolid exposure and can be transmitted between patients in a hospital setting.

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Section: Discussionsupporting

confidence: 72%

Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen

et al. 2023

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“…VRE infections result in increased morbidity, mortality, and medical costs, necessitating a comprehensive treatment strategy involving all infection control professionals [199]. Certainly, the advent of VRE strains highlights the pressing need for brand-new antimicrobial drugs [200,201]. Treatment options for VRE infections mainly include linezolid as the only FDA-approved therapeutical choice.…”

Section: Challenges In Treatment Of Vre Infectionmentioning

confidence: 99%

The Impact of Enterococcus spp. in the Immunocompromised Host: A Comprehensive Review

Sangiorgio,

Calvo,

Migliorisi

et al. 2024

Pathogens

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The immunocompromised host is usually vulnerable to infectious diseases due to broad-spectrum treatments and immunological dysregulation. The Enterococcus genus consists of normal gut commensals, which acquire a leading role in infective processes among individuals with compromised immune systems. These microorganisms may express a potential virulence and resistance spectrum, enabling their function as severe pathogens. The Enterococcus spp. infections in immunocompromised hosts appear to be difficult to resolve due to the immunological response impairment and the possibility of facing antimicrobial-resistant strains. As regards the related risk factors, several data demonstrated that prior antibiotic exposure, medical device insertion, prolonged hospitalization and surgical interventions may lead to Enterococcus overgrowth, antibiotic resistance and spread among critical healthcare settings. Herein, we present a comprehensive review of Enterococcus spp. in the immunocompromised host, summarizing the available knowledge about virulence factors, antimicrobial-resistance mechanisms and host-pathogen interaction. The review ultimately yearns for more substantial support to further investigations about enterococcal infections and immunocompromised host response.

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“…As E. faecium gained more MDR, less traditional antibiotic agents have demonstrated inhibitory or bactericidal activity. Compared to its fellow species E. faecalis , E. faecium has formed the bulk of most VRE infections ( Ayobami et al., 2020 ; Penven et al., 2022 ). The phenotypic antimicrobial susceptibility testing results received at the French National Reference center revealed that none of the 34 E. faecalis clinical isolates was resistant to vancomycin, ampicillin, or teicoplanin, whereas majority of the E. faecium clinical isolates exhibited resistance to vancomycin (85.5%), ampicillin (99.3%), or teicoplanin (73.9%) ( Penven et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Compared to its fellow species E. faecalis , E. faecium has formed the bulk of most VRE infections ( Ayobami et al., 2020 ; Penven et al., 2022 ). The phenotypic antimicrobial susceptibility testing results received at the French National Reference center revealed that none of the 34 E. faecalis clinical isolates was resistant to vancomycin, ampicillin, or teicoplanin, whereas majority of the E. faecium clinical isolates exhibited resistance to vancomycin (85.5%), ampicillin (99.3%), or teicoplanin (73.9%) ( Penven et al., 2022 ). It is believed that intrinsic processes help E. faecium acquire MDR, such as mutations that promote resistance against tigecycline that probably remains the last effective antibiotic against MDR E. faecium ( Cattoir and Giard, 2014 ), since mutations of the rpsJ gene encoding the 30S ribosome protein S10 could reduce tigecycline susceptibility ( Cattoir et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against Enterococcus faecium 1449 drug resistant biofilms

Limayem

Mehta

Kondos

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionSilver (Ag) nanoparticles (NPs) are well documented for their broad-spectrum bactericidal effects. This study aimed to test the effect of bioactive Ag-hydrosol NPs on drug-resistant E. faecium 1449 strain and explore the use of artificial intelligence (AI) for automated detection of the bacteria.MethodsThe formation of E. faecium 1449 biofilms in the absence and presence of Ag-hydrosol NPs at different concentrations ranging from 12.4 mg/L to 123 mg/L was evaluated using a 3-dimentional culture system. The biofilm reduction was evaluated using the confocal microscopy in addition to the Transmission Electronic Microscopy (TEM) visualization and spectrofluorimetric quantification using a Biotek Synergy Neo2 microplate reader. The cytotoxicity of the NPs was evaluated in human nasal epithelial cells using the MTT assay. The AI technique based on Fast Regional Convolutional Neural Network architecture was used for the automated detection of the bacteria.ResultsTreatment with Ag-hydrosol NPs at concentrations ranging from 12.4 mg/L to 123 mg/L resulted in 78.09% to 95.20% of biofilm reduction. No statistically significant difference in biofilm reduction was found among different batches of Ag-hydrosol NPs. Quantitative concentration-response relationship analysis indicated that Ag-hydrosol NPs exhibited a relative high anti-biofilm activity and low cytotoxicity with an average EC50 and TC50 values of 0.0333 and 6.55 mg/L, respectively, yielding an average therapeutic index value of 197. The AI-assisted TEM image analysis allowed automated detection of E. faecium 1449 with 97% ~ 99% accuracy.DiscussionConclusively, the bioactive Ag-hydrosol NP is a promising nanotherapeutic agent against drug-resistant pathogens. The AI-assisted TEM image analysis was developed with the potential to assess its treatment effect.

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Web-based prediction of antimicrobial resistance in enterococcal clinical isolates by whole-genome sequencing

Cited by 4 publications

References 34 publications

Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen

Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen

The Impact of Enterococcus spp. in the Immunocompromised Host: A Comprehensive Review

Evaluation of bactericidal effects of silver hydrosol nanotherapeutics against Enterococcus faecium 1449 drug resistant biofilms

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