scholarly journals 178. Endemic Carbapenem Resistance Driven By Clonal and Horizontal Spread of blaIMP-4 Across Diverse Enterobacterales: Jumping Genes, Promiscuous Plasmids and Killer Clones

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S109-S109
Author(s):  
Nenad Macesic ◽  
Luke Blakeway ◽  
Adam W Jenney ◽  
Anton Peleg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
De Novo ◽  
Bacterial Species ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Hybrid Assembly ◽  
Colistin Resistance ◽  
Resistance Determinants ◽  
Enterobacter Cloacae Complex ◽  
Plasmid Replicons

Abstract Background Carbapenem-resistant Enterobacterales (CRE) have become endemic and cause significant morbidity and mortality globally. The metallo-beta-lactamase gene blaIMP-4 is a key CRE resistance determinant in Australia and Asia but its genomic context remains unknown. We aimed to determine the genomic epidemiology of blaIMP-4 in clinical and environmental isolates from 2008 – 2020 at our institution. Methods We performed whole genome sequencing on 219 blaIMP-4-carrying isolates from 134 patients (219 short-read and 75 long-read). Multi-locus sequence types (MLSTs), resistance determinants and plasmid replicons were assessed. High-quality de novo hybrid assemblies were used to identify location of blaIMP-4 gene. We conducted phylogenetic analysis for key MLSTs and plasmids. Results Bla IMP-4 was noted on a class I integron also harboring aminoglycoside, sulfamethoxazole, chloramphenicol and quaternary ammonium compound resistance genes. This integron was able to migrate over time to 10 bacterial species (42 STs) and 6 different plasmid types (Figure 1 and Figure 2). From 2008-2020, blaIMP-4 was present on IncC plasmids in Serratia marcescens and Klebsiella pneumoniae. We noted small outbreaks of Pseudomonas aeruginosa ST111 with chromosomal integration of blaIMP-4 from 2008-2018 (16 isolates) and Enterobacter cloacae complex ST114 with blaIMP-4 on IncFIB(K)/IncFIA(HI1) plasmids from 2011-2020 (19 isolates). From 2016-2020, there was an explosion of diverse IncHI2 plasmids carrying blaIMP-4. This was driven by clonal expansion of E. cloacae complex ST93/ST190 (79 isolates), with spillover of IncHI2 plasmids to Klebsiella spp (13 isolates), Citrobacter spp (2 isolates), S. marcescens (1 isolate), Escherichia coli (4 isolates). In addition to blaIMP-4, these plasmids carried mcr-9.1, a colistin resistance gene, and resistance determinants to nearly all key classes of Gram-negative antimicrobials. Figure 1. Bacterial species harboring blaIMP-4 2008-2020 BlaIMP-4 was noted in diverse bacterial species over the study period. Serratia marcescens and Klebsiella pneumoniae were present throughout. Outbreaks of Enterobacter cloacae complex ST114, ST190 and ST93 and Pseudomonas aeruginosa ST111 were noted. Figure 2. Diverse plasmids associated with blaIMP-4 carriage determined by de novo hybrid assembly Presence of blaIMP-4 on diverse plasmids that varied through the study period was noted. Plasmids were charaterised by analysing de novo hybrid assembly data and co-location of blaIMP-4 and plasmid replicons on the same contigs. Conclusion Bla IMP-4 spread on a class I integron was responsible for endemic carbapenem resistance at our institution. This mobile genetic element was able to persist due to both clonal spread and entry into diverse plasmids. Concerningly, we noted a large outbreak driven by IncHI2 plasmids harboring colistin resistance genes with spread to multiple bacterial species. Disclosures All Authors: No reported disclosures

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin

2020 ◽  
Author(s):  
Tieli Zhou ◽  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Lipid A ◽  
Efflux Pump ◽  
Medical Center ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Colistin Resistance ◽  
Carbapenemase Gene

Abstract Background: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains.Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed.Results: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). And the mechanism of colistin resistance is increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.Conclusions: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

Phenotypic prevalence of resistance to carbapenems, colistin and genes encoding carbapenemase in Pseudomonas aeruginosa

MedPharmRes ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 18-22
Author(s):  
Mai Thi Thanh Nguyen ◽  
Chuong Van Le ◽  
Phuong Mai Doan ◽  
Chinh Van Nguyen ◽  
Huy Quang Vu
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Effective Treatment ◽  
Resistance Genes ◽  
Real Time Pcr ◽  
Carbapenem Resistance ◽  
Good Effect ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Genes Encoding

Introduction: The production of carbapenem enzyme is one of the most frequent mechanisms reported in cabapenem resistant Pseudomonas aeruginosa. Besides, a growing number of mobile colistin resistance (MCR) genes are threatening the renewed interest of colistin as a "last-resort" against carbapenem-resistant pathogens. Therefore, the detection of carbapenem-resistant and colistin-resistant phenotypes as well as preventing transmission of multi-resistant P. aeruginosa strains with genes coding for carbapenemase is extremely necessary. Material and methods: Among 159 P. aeruginosa strains were collected 46 isolates, which is resistant or intermediated to meropenem. Modified carbapenem inactivation (mCIM) and colistin broth disk elution (CBDE) methods were used to identify carbapenemase-producing strains and colistin resistance. In addition, a multiplex real-time PCR technique was applied to investigate the frequency of emergence of carbapenem resistance genes. Results: The results revealed that 25 strains (54.3%) were positive with mCIM test and none of them resistant to colistin by CBDE method. Number of strains carrying a gene blaIMP: 4 strains (16%), blaNDM: 2 strains (8%). Strains are carrying two genes: blaIMP + blaNDM: 10 strains (40%), blaVIM + blaNDM: 1 strain (4%), blaNDM + blaOXA-48: 1 strain (4%) and are carrying three genes blaIMP + blaNDM + blaOXA-48: 6 strains (24%), blaKPC + blaIMP + blaNDM: 1 strain (4%). Conclusions: All mCIM positive P. aeruginosa were contained carbapenemase genes. Colistin still reserved a good effect to combine with other antibiotics in multi-resistant treatment. Hence, the classification of genes can help clinicians selected appropriate antibiotics so that more effective treatment for patients.

scholarly journals Clonal spread and accumulation of β-lactam resistance determinants in Enterobacter aerogenes and Enterobacter cloacae complex isolates from infection and colonization in patients at a public hospital in Recife, Pernambuco, Brazil

2017 ◽  
Vol 66 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Adriane Borges Cabral ◽  
Maria Amélia Vieira Maciel ◽  
Josineide Ferreira Barros ◽  
Marcelo Maranhão Antunes ◽  
Célia Maria Machado Barbosa de Castro ◽  
...  
Keyword(s):  
Public Hospital ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Resistance Determinants ◽  
Clonal Spread ◽  
Enterobacter Cloacae Complex

scholarly journals Molecular Characterization of KPC-2-Producing Enterobacter cloacae Complex Isolates from Cali, Colombia

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 694
Author(s):  
Aura Falco ◽  
Daniela Guerrero ◽  
Isabella García ◽  
Adriana Correa ◽  
Sandra Rivera ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Public Health Problem ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Epidemiological Surveillance ◽  
Beta Lactam ◽  
High Genetic Diversity ◽  
Effective Prevention ◽  
Enterobacter Cloacae Complex

The Enterobacter cloacae complex is an emerging opportunistic pathogen whose increased resistance to carbapenems is considered a public health problem. This is due to the loss of efficacy of beta-lactam antibiotics, which are used as the first treatment option in the management of infections caused by Gram-negative bacteria. The objective of this study was to perform the molecular characterization of 28 isolates of the E. cloacae complex resistant to cephalosporins and carbapenems isolated between 2011 and 2018 from five hospitals located in the municipality of Santiago de Cali, Colombia. Molecular detection of blaKPC, blaVIM, blaNDM and blaOXA-48-like genes was performed on these isolates and the genetic relationship between the isolates was assessed using multilocus sequence typing (MLST). Forty-three percent of the isolates carried the blaKPC-2 gene variant. MLST showed high genetic diversity among isolates, the most frequent being the sequence type ST510 with a frequency of 50%. The identification of the genes involved in carbapenem resistance and dispersing genotypes is an important step toward the development of effective prevention and epidemiological surveillance strategies in Colombian hospitals.

scholarly journals Interplay of OpdP Porin and Chromosomal Carbapenemases in the Determination of Carbapenem Resistance/Susceptibility in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Jad Atrissi ◽  
Annalisa Milan ◽  
Raffaela Bressan ◽  
Marianna Lucafò ◽  
Vincenzo Petix ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Content Type ◽  
Resistance Determinants ◽  
Multiple Factors ◽  
The Impact

This study examines the interplay of multiple factors in determining a pattern of resistance or susceptibility to carbapenems in clinical isolates of Pseudomonas aeruginosa , focusing on the role of previously poorly understood determinants. In particular, the impact of carbapenem permeability through OprD and OpdP porins was analyzed, as well as the activity of the chromosomal carbapenemases AmpC and PoxB, going beyond the simple identification of resistance determinants encoded by each isolate.

Clinical and molecular characterization of Acinetobacter seifertii in Taiwan

2020 ◽  
Author(s):  
Li-Hua Li ◽  
Ya-Sung Yang ◽  
Jun-Ren Sun ◽  
Tzu-Wen Huang ◽  
Wei-Cheng Huang ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Clinical Information ◽  
Molecular Characteristics ◽  
Close Monitoring ◽  
Colistin Resistance ◽  
Resistance Determinants ◽  
Drug Of Choice ◽  
Mlst Type ◽  
Severe Infections ◽  
Independent Risk Factors

Abstract Objectives Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. Patients and methods This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments. Results The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii. Conclusions Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring.

scholarly journals Distribution of carbapenem resistance determinants among epidemic and non-epidemic types of Acinetobacter species in Japan

2014 ◽  
Vol 63 (6) ◽  
pp. 870-877 ◽  
Author(s):  
Mari Matsui ◽  
Satowa Suzuki ◽  
Kunikazu Yamane ◽  
Masato Suzuki ◽  
Toshifumi Konda ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
The Other ◽  
Fluoroquinolone Resistance ◽  
Pasteur Institute ◽  
Acinetobacter Species ◽  
Resistance Determinants ◽  
Sequence Types

We performed a comparative molecular analysis on three types of clinically isolated Acinetobacter spp.: epidemic sequence types (STs) of Acinetobacter baumannii (epidemic ST-AB), non-epidemic sequence types of A. baumannii (non-epidemic ST-AB) and non-baumannii Acinetobacter spp. A total of 87 isolates – 46 A. baumannii, 25 A. pittii and 16 A. nosocomialis – from 43 hospitals were analysed. Of these, 31 A. baumannii isolates were ST1 or ST2 according to the Pasteur Institute multilocus sequence typing scheme and were defined as epidemic ST-AB. The other 15 A. baumannii isolates were defined as non-epidemic ST-AB. The epidemic ST-AB isolates harboured the bla OXA-23-like gene or had an ISAba1 element upstream of bla OXA-51-like, or both, whereas non-epidemic ST-AB and non-baumannii Acinetobacter spp. isolates harboured bla OXA-58-like or metallo-β-lactamase genes, or both. The proportion of multidrug-resistant isolates was significantly higher in the epidemic ST-AB isolates (48 %) than that in the other types of Acinetobacter isolates (5 %) (P<0.05). In addition, epidemic ST-AB isolates exhibited a relatively higher proportion of fluoroquinolone resistance. We demonstrated that, in terms of genotypes and phenotypes of antimicrobial resistance, non-epidemic ST-AB isolates shared more similarity with non-baumannii Acinetobacter spp. isolates than with epidemic ST-AB isolates, regardless of bacterial species. In addition, this study revealed that, even in Japan, where IMP-type metallo-β-lactamase producers are endemic, epidemic ST-AB harbouring bla IMP have not yet emerged.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin

2021 ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Lipid A ◽  
Efflux Pump ◽  
Medical Center ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Colistin Resistance ◽  
Carbapenemase Gene

Abstract Background: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Genetic clusters of based on hsp60 sequence analysis were performed. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed. Results: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.Conclusions: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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