Multicenter Clinical Evaluation of ETEST Eravacycline for Susceptibility Testing of
            <i>Enterobacteriaceae</i>
            and Enterococci

Blanchard, Laurine; Armstrong, Thomas P; Kresken, Michael; Emery, Christopher L.; Yu, Ying; Sauvonnet, Véronique; Zambardi, Gilles

doi:10.1128/jcm.01650-22

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…ERV, a novel fluorocycline antibiotic, is a fourth-generation tetracycline introduced after tigecycline ( Blanchard et al, 2023 ). It acts as an antimicrobial agent by reversibly binding to the bacterial ribosomal 30S subunit, thereby preventing amino acid residues from being incorporated into elongating peptide chains, which leads to the disruption of bacterial protein synthesis ( Zhanel et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…With evidence indicating that CRKP could render colistin treatments ineffective, eravacycline (ERV) could be considered a last-resort drug for the treatment of CRKP infections, especially in countries where colistin is not commercially available. ERV, a novel fluorocycline antibiotic, is a fourth-generation tetracycline introduced after tigecycline (Blanchard et al, 2023). It acts as an antimicrobial agent by reversibly binding to the bacterial ribosomal 30S subunit, thereby preventing amino acid residues from being incorporated into elongating peptide chains, which leads to the disruption of bacterial protein synthesis (Zhanel et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates

Zhang,

Liu,

Liu

et al. 2024

Front. Microbiol.

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Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates

Zhang,

Liu,

Liu

et al. 2024

Front. Microbiol.

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In vitro activities of eravacycline against clinical bacterial isolates: a multicenter study in Guangdong, China

Liao,

Liang,

Dai

et al. 2024

Front. Microbiol.

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IntroductionEravacycline (ERV), a novel tetracycline derivative, exhibits broad-spectrum antibacterial activity, but data on the bacterial activity against Chinese bacterial isolates are very scarce. This study aims to evaluate the activity of eravacycline against the common Gram-positive and Gram-negative bacteria isolates in Guangdong, China.MethodsThe clinical isolates were collected from four centers between 1 November 2023 and 31 January 2024, and the susceptibility of eravacycline (MIC50, MIC90, and MIC) was determined using broth microdilution as a reference method and E-TEST strips to evaluate their consistency. A total of 594 strains were collected from the four centers, including Staphylococcus aureus (n = 126), Enterococcus faecalis (n = 58), Enterococcus faecium (n = 29), Klebsiella pneumoniae (n = 136), Escherichia coli (n = 187), and Acinetobacter baumannii (n = 58).Results and discussionThe MIC50 and MIC90 (mg/L) of eravacycline were 0.12 and 1 for S. aureus, 0.06 and 0.12 for E. faecalis, 0.06 and 0.5 for E. faecium, 0.25 and 0.5 for E. coli, 0.5 and 2 for K. pneumoniae, and 0.25 and 2 for A. baumannii. Based on the FDA and EUCAST breakpoints, the susceptibility of eravacycline against S. aureus was 46.03% vs. 83.33%, 56.90% vs. 94.93% against E. faecalis, and 62.07% vs. 79.31% in E. faecium. The susceptibility rates of E. coli and K. pneumoniae were 90.37% and 58.09, respectively. To evaluate the performance between the broth microdilution test (BMD) and ETEST methods, we compared essential agreement (EA), categorical agreement (CA), very major error (VME), and major error (ME). The results demonstrated that compared with BMD, eravacycline measured by ETEST had higher VME and ME referring to FDA breakpoints than EUCAST breakpoints in the Gram-positive isolates. Since there were no intermediate breakpoints for the eravacycline, the MIC values measured by the ETEST method might result in lower CA and higher VME and ME. This study provides MIC values of eravacycline against Gram-positive and Gram-negative pathogens in four hospitals in Guangdong Province, and eravacycline is an effective therapeutic candidate for common bacteria.

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Colistin, Meropenem–Vaborbactam, Imipenem–Relebactam, and Eravacycline Testing in Carbapenem-Resistant Gram-Negative Rods: A Comparative Evaluation of Broth Microdilution, Gradient Test, and VITEK 2

Forstner,

Fuchs,

Luxner

et al. 2024

Antibiotics

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Objectives. This study aimed to evaluate and compare the performance of different assays for antimicrobial susceptibility testing (AST) and minimum inhibitory concentration (MIC) determination for reserve antibiotics in carbapenem-resistant Enterobacterales (CREs), Pseudomonas aeruginosa (CRPAs), and Acinetobacter baumannii (CRABs). Methods. An analysis was conducted on 100 consecutive isolates: 50 CREs, 35 CRPAs, and 15 CRABs. Sensititre broth microdilution was used as a reference standard to evaluate the performance of VITEK 2 card AST-XN24 (bioMérieux), the respective gradient tests (bioMérieux), and UMIC colistin broth microdilution test strips (Bruker Daltonics). Errors, essential agreement (EA), and categorical agreement of MICs for colistin (COL), meropenem–vaborbactam (MVB), imipenem–relebactam (IRL), and eravacycline (ERV) were assessed. Results. The agreement between both of the COL broth microdilution (BMD) methods was perfect (100/100). The gradient test and VITEK 2 analysis yielded comparable EA rates (92/100 and 72/79, respectively), with the latter not registering any very major errors (VMEs). The MVB gradient test achieved EA in 66 of 85 isolates and VITEK 2 in 70/85. For IRL, EA was reached in 69 and 64 of 85 cases by gradient test and VITEK 2 analysis, respectively. The ERV gradient test yielded false results in nearly all (12/15) CRABs but achieved EA in 46 of 50 CREs. The VITEK system recorded EA for ERV in 60 of 65 isolates. Conclusions. We observed substantial variability in the measured MICs between BMD and the alternative methods. In only a few constellations, VITEK 2 or gradient tests could substitute the reference method. BMD is the method of choice for COL analysis, with VITEK 2 representing an alternative method for CRPA testing. Alternative methods for MVB did not provide reliable results, except for Enterobacterales, when tested with the gradient test. However, resistant results need to be confirmed by BMD. Only BMD can be used for IRL MIC determination. VITEK 2 was mostly accurate in measuring ERV MICs, while the corresponding gradient test yielded reliable results exclusively in CREs. It is essential that laboratories are aware of which testing method provides reliable results for each combination of microorganisms and reserve antibiotics.

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Multicenter Clinical Evaluation of ETEST Eravacycline for Susceptibility Testing of Enterobacteriaceae and Enterococci

Abstract: Eravacycline (ERV) (brand name Xerava [Tetraphase]) is a new tetracycline-class antibacterial that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of complicated intra-abdominal infections (cIAIs).

Cited by 3 publications

References 10 publications

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates

In vitro activities of eravacycline against clinical bacterial isolates: a multicenter study in Guangdong, China

Colistin, Meropenem–Vaborbactam, Imipenem–Relebactam, and Eravacycline Testing in Carbapenem-Resistant Gram-Negative Rods: A Comparative Evaluation of Broth Microdilution, Gradient Test, and VITEK 2

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