Dataset Information

Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China.

ABSTRACT: Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.

SUBMITTER: Wang Y

PROVIDER: S-EPMC10993752 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature

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Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China.

Wang Yinping Y Hu Huangdu H Shi Qiucheng Q Zhang Ping P Zhao Dongdong D Jiang Yan Y Yu Yunsong Y

Emerging microbes & infections 20240403 1

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resista ...[more]

PMID: 38517707

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Project description:Purpose: The infection of carbapenem-resistant Enterobacterales (CRE) has become a major clinical and healthcare problem worldwide. The screening methods of CRE have been extensively developed but still need improving [e.g., tests with accurate and simple minimum inhibitory (MICs)]. In this study, the performance of the BD Phoenix NMIC-413 AST panel was evaluated against clinical CRE and carbapenem-susceptible Enterobacterales (CSE) in China. The panel was first evaluated in the Chinese clinical lab. Methods: Antimicrobial susceptibility testing of 303 clinical Enterobacterales isolates were conducted by broth microdilution (BMD), Phoenix NMIC-413 AST panel, and disk diffusion method for imipenem, ertapenem, and meropenem. Considering BMD is a gold standard, essential agreement (EA), categorical agreement (CA), minor error (MIE), major error (ME), and very major error (VME) were determined according to CLSI guidelines. CA and EA > 90%, ME <3%, and VME <1.5% were considered as acceptable criteria. Polymerase chain reaction and sanger sequencing were performed to determine the β-lactamase genotypes of CRE isolates. Results: Three hundred and three isolates included 195 CREs and 108 CSEs were enrolled according to the BMD-MIC values of three carbapenems. Tested CREs showing 100 bla KPC-2-positive organisms, 31 bla IMP-positive organisms, 28 bla NDM-positive organisms, 5 bla VIM-positive organisms, 2 both bla IMP and bla VIM-positive organisms, 2 bla OXA-48-positive organisms, and 27 isolates without carbapenemase genes. For the Phoenix NMIC-413 method, CA and EA rates >93%, MIE rates <5%, ME rates <1.75%, and VME rates were 0%, across the three drugs. For the disk diffusion method, the CA rates for three drugs were all >93%, while the MIE and ME rates were all <5 and <3%, respectively. VME rate was 3.28% for imipenem, exceeded the cut-off value specified by CLSI M52, 0 and 0.56% for ertapenem and meropenem, separately. Conclusion: Based on the genomic data, the detection of CRE and CSE was more reliable using the BD Phoenix NMIC-413 panel compared to the BMD and disk approaches. Therefore, our study supports the use of BD Phoenix NMIC-413 panel as a suitable alternative to BMD for the detection of carbapenem resistant isolates in a clinical setting.

Project description:ObjectiveThis retrospective study was conducted to determine the prevalence and molecular epidemiology characteristics of carbapenem-resistant Escherichia coli (CRE).MethodsA total of 593 Escherichia coli (E. coli) isolates were recovered from pigs and urban river from 2009 to 2014 in Heilongjiang Province of China. Forty CRE including 22 strains isolated from fecal samples of pigs and 18 strains isolated from water samples were selected. PCR detection of resistance determinants, multi-locus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and phylogenetic groups were performed to characterize CRE isolates. Conjugation experiments, plasmid stability testing, PCR-based replicon typing (PBRT), and PCR mapping were conducted to analyze bla NDM-carrying plasmids. In vitro time-growth studies and competition experiments were carried out to assess the fitness impact of NDM carriage.ResultsFive NDM-1-positive E. coli isolates were identified from water samples. Genetic environment analysis revealed that a cluster of genes (ISAba125-bla NDM-1-ble MBL-ΔtrpF) was detected in all of the NDM-1-positive isolates. Conjugation assays showed that bla NDM-1 could be successfully transferred to E. coli J53 from 5 donor strains at frequencies of 4.6×10-5 to 2.6×10-2. The plasmids from all transconjugants belonged to different plasmid replicon types including IncA/C (n=2), IncFII (n=1) and IncX3 (n=2). In vitro time-growth studies revealed that bla NDM-1 did not have a significant impact on cell proliferation. Meanwhile, competition experiments showed that the acquisition of bla NDM-1 can place an energy burden on the bacterial host and incur fitness cost. However, plasmid stability testing showed that bla NDM-1-carrying plasmid remained stable in the hosts after seven passages without antimicrobial selection.ConclusionThe study revealed the early molecular epidemiology and dissemination characteristics of CRE. In addition, the overall antimicrobial resistance in E. coli recovered from water samples is higher than the strains isolated from fecal samples of pigs. Furthermore, we isolated and identified five NDM-1-producing E. coli strains from water samples.

Project description:The activities of meropenem-vaborbactam and comparators against 152 (1.1%) carbapenem-resistant Enterobacterales (CRE) isolates identified among 13,929 Enterobacterales isolates collected from U.S. hospitals during 2016 to 2018 were evaluated. CRE rates were higher in the Middle Atlantic census division (3.5%) than in the other divisions (range, 0.0% for the West North Central division to 1.4% for the West South Central division). Among the CRE isolates, 134 carried carbapenemase genes, and these included 72 isolates carrying blaKPC-3, 51 isolates carrying blaKPC-2, 4 isolates carrying blaNDM-1, 3 isolates carrying blaSME-4, 2 isolates carrying blaVIM-1, 1 isolate carrying blaOXA-232, and 1 isolate carrying blaKPC-4 Meropenem-vaborbactam was active against 95.4% of the CRE isolates and 94.8% of the carbapenem-producing Enterobacterales (CPE) isolates when applying the CLSI breakpoints. All isolates producing serine carbapenemases were inhibited by meropenem-vaborbactam at ≤8 mg/liter. One Citrobacter freundii isolate carrying blaKPC-3 had a meropenem-vaborbactam MIC of 8 mg/liter and was resistant according to CLSI breakpoints (the isolate was susceptible when the EUCAST criterion of an MIC of ≤8 mg/liter for susceptible was applied), had disrupted OmpC and OmpF sequences, and overexpressed AcrAB-TolC. All carbapenemase-negative CRE isolates (n = 18) were inhibited by meropenem-vaborbactam at ≤4 mg/liter, and the MIC values of this combination ranged from 0.25 to 4 mg/liter. Among 7 isolates carrying metallo-β-lactamases and/or oxacillinases with carbapenemase activity, meropenem-vaborbactam susceptibility was 14.3% and 57.1% when applying CLSI and EUCAST breakpoints, respectively. CRE isolates were resistant to many comparator agents, and the most active agents were tigecycline, colistin, and amikacin (to which 63.2% to 96.7% of the isolates were susceptible). Understanding the epidemiology of CRE isolates in U.S. hospitals and the resistance mechanisms among these isolates is important to form guidelines for the treatment of infections caused by these organisms, which have high mortality rates.

Dataset Information

Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China.

Publications

Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China.

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