Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China

Wang, Dongliang; Wang, Minggui; He, Tianpeng; Li, Dan; Zhang, Liqin; Zhang, Dongquan; Feng, Junshuai; Yang, Wen-Li; Yuan, Yuan

doi:10.3389/fmicb.2022.974990

Cited by 5 publications

(5 citation statements)

References 20 publications

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“…In this study, eight CRKP isolates did not produce any carbapenemases, and six of them were resistant to ertapenem only, but were susceptible to meropenem and imipenem. A previous study of our research group demonstrated that mutations in ramR caused the over-expression of efflux pump and the inhibition of outer membrane protein OmpK35, which was implicated in ertapenem resistance only in K. pneumoniae including the six isolates in this study ( Wang D. et al, 2022 ).…”

Section: Discussionmentioning

confidence: 64%

Coexistence of blaKPC-IncFII plasmids and type I-E* CRISPR-Cas systems in ST15 Klebsiella pneumoniae

Jiang

Wang

et al. 2023

Front. Microbiol.

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The CRISPR-Cas system in Klebsiella pneumoniae can prevent the entry of blaKPC-IncF plasmids. However, some clinical isolates bear the KPC-2 plasmids despite carrying the CRISPR-Cas system. The purpose of this study was to characterize the molecular features of these isolates. A total of 697 clinical K. pneumoniae isolates were collected from 11 hospitals in China, and tested for the presence of CRISPR-Cas systems using polymerase chain reaction. Overall, 164 (23.5%) of 697 K. pneumoniae isolates had type I-E* (15.9%) or type I-E (7.7%) CRISPR-Cas systems. The most prevalent sequence type among isolates carrying type I-E* CRISPR was ST23 (45.9%), followed by ST15 (18.9%). Isolates with CRISPR-Cas system were more susceptible to ten antimicrobials tested, including carbapenems, compared with the CRISPR-negative isolates. However, there were still 21 CRISPR-Cas-carrying isolates that showed resistance to carbapenems, and these isolates were subjected to whole-genome sequencing. Thirteen of these 21 isolates carried blaKPC-2-bearing plasmids, of which nine had a new plasmid type, IncFIIK34, and two had IncFII(PHN7A8) plasmids. In addition, 12 of these 13 isolates belonged to ST15, while only eight (5.6%, 8/143) isolates belonged to ST15 in carbapenem-susceptible K. pneumoniae carrying CRISPR-Cas systems. In conclusion, we found that blaKPC-2-bearing IncFII plasmids could co-exist with the type I-E* CRISPR-Cas systems in ST15 K. pneumoniae.

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Section: Discussionmentioning

confidence: 64%

Coexistence of blaKPC-IncFII plasmids and type I-E* CRISPR-Cas systems in ST15 Klebsiella pneumoniae

Jiang

Wang

et al. 2023

Front. Microbiol.

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“…To date, few studies have assessed the proportion of ETP-mono-resistant CRE strains in the total CRE population. A large, geographically diverse study in the US found that 62.2% of CRE cases were resistant only to ertapenem among carbapenems [ 12 ], while another study conducted in China found that 7.4% of CRKP strains were resistant to ertapenem but susceptible to other carbapenems [ 13 ]. In our study, 18.8% of CRE strains were ETP-mono-resistant.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, 18.8% of CRE strains were ETP-mono-resistant. Only 2.4% of ETP-mono-resistant CRE isolates possessed any carbapenemase gene in the US study [ 12 ], while none of the strains resistant to ertapenem but susceptible to other carbapenems contained a carbapenemase gene in the study conducted in China [ 13 ]. In our study, 18.5% of ETP-mono-resistant strains were positive for carbapenemase genes.…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, these strains are still susceptible or intermediate to meropenem and imipenem, namely, ertapenem-mono-resistant (ETP-mono-resistant) CRE strains [ 11 ]. Reports of ETP-mono-resistant CRE strains are emerging more frequently, with a low prevalence of carbapenemase genes in these strains [ 12 , 13 ]. Nonetheless, the presence of carbapenemases in ETP-mono-resistant CRE strains poses challenges to appropriate therapeutic options [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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

Wang,

Hu,

Shi

et al. 2024

Emerging Microbes & Infections

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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.

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“…10 Previous studies have used WGS to characterize CRPK isolates from local hospitals and their susceptibility to commonly used antibiotics are urgently needed for improved clinical guidance. [11][12][13] However, the reports from Wuhan China are limited. Our study explored the antibiotic resistance genes, virulence factors and action mechanisms of CRKP through antimicrobial susceptibility tests and WGS technology, to screen common antibiotic resistance genes, so as to further guide the rational and standardized use of antibiotics in the clinic, which hopefully to effectively reduce and control CRKP occurrence.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China

Fan¹,

Lin²,

Mou³

et al. 2023

IDR

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Background: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance. Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain's identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology. Results:The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049. Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.

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Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China

Cited by 5 publications

References 20 publications

Coexistence of blaKPC-IncFII plasmids and type I-E* CRISPR-Cas systems in ST15 Klebsiella pneumoniae

Coexistence of blaKPC-IncFII plasmids and type I-E* CRISPR-Cas systems in ST15 Klebsiella pneumoniae

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

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China

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