Epidemiology of Acquired AmpC Type β-Lactamases in Enterobacteriaceae from a One Health Perspective

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 15276

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UCIBIO-REQUIMTE. Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Porto, Portugal
Interests: clinical Bacteriology; enterobacteriaceae; molecular epidemiology; mechanisms of Resistance; mobile genetic elements; population structure; bacterial typing methods; virulence genetics; molecular spectroscopy

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UCIBIO/REQUIMTE, Laboratório de Microbiologia, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
Interests: urogenital microbiome; bacterial taxonomy; Lactobacillaceae; mobile genetic elements; bacteriocins; antimicrobial resistance
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Special Issue Information

Dear Colleagues,

Resistance to third-generation cephalosporins amongst Enterobacteriaceae is endemic in many parts of the world, and molecular epidemiology in different settings is very well characterized in what concerns the production of extended-spectrum beta-lactamases (ESBLs). However, the contribution of acquired AmpC beta-lactamases is probably underestimated due to constraints in routine laboratory detection, and the absence of comprehensive studies at a wide inter- and intraspecies population levels addressing the interplay between different ecological niches (humans, animals, and the environment). The focus of this Special Issue is the occurrence and molecular epidemiology of bacterial species carrying acquired AmpC beta-lactamases within and between different hosts and environments. Review and research papers on the detection and treatment of infections in a clinical setting, whole-genome-based studies on population and mobile genetic elements encoding acquired AmpC beta-lactamases, or risk assessment of antibiotic resistance transmission are also encouraged.

Dr. Ângela Novais
Dr. Teresa G Ribeiro
Guest Editors

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Keywords

  • antibiotic resistance
  • acquired AmpC beta-lactamases
  • surveillance
  • molecular epidemiology
  • One Health
  • population structure
  • mobile genetic elements typing
  • transmission of antibiotic resistance
  • genomics and bioinformatics
  • infection control

Published Papers (6 papers)

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Research

15 pages, 324 KiB  
Article
The Resistance Mechanisms and Clinical Impact of Resistance to the Third Generation Cephalosporins in Species of Enterobacter cloacae Complex in Taiwan
by Chung-Yu Chang, Po-Hao Huang and Po-Liang Lu
Antibiotics 2022, 11(9), 1153; https://doi.org/10.3390/antibiotics11091153 - 26 Aug 2022
Cited by 6 | Viewed by 1658
Abstract
Enterobacter cloacae complex (ECC) is ubiquitous in the environment and is an important pathogen causing nosocomial infections. Because routine methods used in clinical laboratories cannot identify species within ECC, the clinical significance of each species within ECC is less known. We applied hsp60 [...] Read more.
Enterobacter cloacae complex (ECC) is ubiquitous in the environment and is an important pathogen causing nosocomial infections. Because routine methods used in clinical laboratories cannot identify species within ECC, the clinical significance of each species within ECC is less known. We applied hsp60 gene sequencing to identify the species/clusters of ECC and detected β-lactamase genes and class 1 integrons with PCR for 184 clinical ECC isolates in Taiwan from 2013 to 2014 to investigate the clinical impact of species within ECC. The four most common clusters were E. hormaechei subsp. steigerwaltii (cluster VIII) (29.9%), E. hormaechei subsp. oharae (cluster VI) (20.1%), E. cloacae subsp. cloacae (cluster XI) (12%), and E. kobei (cluster II) (10.3%). E. hormaechei, which consisted of four clusters (clusters III, VI, VII, and VIII), is the predominant species and accounted for 57.1% of the isolates. The ceftazidime resistance rate was 27.2%, and the ceftriaxone resistance rate was 29.3%. Resistance to third generation cephalosporin was associated with a higher 30-day mortality rate. In total, 5 (2.7%), 24 (13.0%), and 1 (0.5%) isolates carried ESBL, AmpC, and carbapenemase genes, respectively. Class 1 integrons were present in 24.5% of the isolates, and most of the cassettes pertain to antibiotic resistance. Resistance to third generation cephalosporins, multidrug resistance, and class 1 integrons were significantly more in E. hormaechei (clusters III, VI, VII, and VIII) than in the other species. The 30-day mortality rate and 100-day mortality did not differ significantly between patients with E. hormaechei and those with infections with the other species. In conclusion, the distribution of third generation cephalosporin resistance, multidrug resistance, and class 1 integrons were uneven among Enterobacter species. The resistance to third generation cephalosporins possessed significant impact on patient outcome. Full article
9 pages, 1615 KiB  
Article
Rapid Detection of Plasmid AmpC Beta-Lactamases by a Flow Cytometry Assay
by Inês Martins-Oliveira, Blanca Pérez-Viso, Ana Silva-Dias, Rosário Gomes, Luísa Peixe, Ângela Novais, Rafael Cantón and Cidália Pina-Vaz
Antibiotics 2022, 11(8), 1130; https://doi.org/10.3390/antibiotics11081130 - 19 Aug 2022
Cited by 1 | Viewed by 1501
Abstract
Plasmidic AmpC (pAmpC) enzymes are responsible for the hydrolysis of extended-spectrum cephalosporins but they are not routinely investigated in many clinical laboratories. Phenotypic assays, currently the reference methods, are cumbersome and culture dependent. These methods compare the activity of cephalosporins with and without [...] Read more.
Plasmidic AmpC (pAmpC) enzymes are responsible for the hydrolysis of extended-spectrum cephalosporins but they are not routinely investigated in many clinical laboratories. Phenotypic assays, currently the reference methods, are cumbersome and culture dependent. These methods compare the activity of cephalosporins with and without class C inhibitors and the results are provided in 24–48 h. Detection by molecular methods is quicker, but several genes should be investigated. A new assay for the rapid phenotypic detection of pAmpC enzymes of the Enterobacterales group-I (not usually AmpC producers) based on flow cytometry technology was developed and validated. The technology was evaluated in two sites: FASTinov, a spin-off of Porto University (Portugal) where the technology was developed, and the Microbiology Department of Ramón y Cajal University Hospital in Madrid (Spain). A total of 100 strains were phenotypically screened by disk diffusion for the pAmpC with the new 2 h assay. Molecular detection of the pAmpC genes was also performed on discrepant results. Forty-two percent of the strains were phenotypically classified as pAmpC producers using disk diffusion. The percentage of agreement of the flow cytometric assay was 93.0%, with 95.5% sensitivity and 91.1% specificity. Our proposed rapid assay based on flow cytometry technology can, in two hours, accurately detect pAmpC enzymes. Full article
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18 pages, 2005 KiB  
Article
Molecular Epidemiology of Extended-Spectrum Beta-Lactamase and AmpC Producing Enterobacteriaceae among Sepsis Patients in Ethiopia: A Prospective Multicenter Study
by Melese Hailu Legese, Daniel Asrat, Abraham Aseffa, Badrul Hasan, Adane Mihret and Göte Swedberg
Antibiotics 2022, 11(2), 131; https://doi.org/10.3390/antibiotics11020131 - 19 Jan 2022
Cited by 13 | Viewed by 3051
Abstract
Extended-spectrum beta-lactamases (ESBLs) and AmpC producing Enterobacteriaceae are public health threats. This study aims to characterize ESBL and AmpC producing Enterobacteriaceae isolated from sepsis patients. A multicenter study was conducted at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) [...] Read more.
Extended-spectrum beta-lactamases (ESBLs) and AmpC producing Enterobacteriaceae are public health threats. This study aims to characterize ESBL and AmpC producing Enterobacteriaceae isolated from sepsis patients. A multicenter study was conducted at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) and northern (Dessie) parts of Ethiopia. Blood culture was performed among 1416 sepsis patients. Enterobacteriaceae (n = 301) were confirmed using MALDI-TOF and subjected for whole genome sequencing using the Illumina (HiSeq 2500) system. The overall genotypic frequencies of ESBL and AmpC producing Enterobacteriaceae were 75.5% and 14%, respectively. The detection of ESBL producing Enterobacteriaceae at Hawassa, Yekatit 12, Tikur Anbessa and Dessie was 95%, 90%, 82% and 55.8%, respectively. The detection frequency of blaCTX-M, blaTEM and blaSHV genes was 73%, 63% and 33%, respectively. The most frequently detected ESBL gene was blaCTX-M-15 (70.4%). The common AmpC genes were blaACT (n = 22) and blaCMY (n = 13). Of Enterobacteriaceae that harbored AmpC (n = 42), 71% were ESBL co-producers. Both blaTEM-1B (61.5%) and blaSHV-187 (27.6%) were the most frequently detected variants of blaTEM and blaSHV, respectively. The molecular epidemiology of ESBL producing Enterobacteriaceae showed high frequencies and several variants of ESBL and AmpC genes. Good antimicrobial stewardship and standard bacteriological laboratory services are necessary for the effective treatment of ESBL producing Enterobacteriaceae. Full article
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13 pages, 916 KiB  
Article
Taxonomic Identification of Different Species of the Genus Aeromonas by Whole-Genome Sequencing and Use of Their Species-Specific β-Lactamases as Phylogenetic Markers
by Xavier Bertran, Marc Rubio, Laura Gómez, Teresa Llovet, Carme Muñoz, Ferran Navarro and Elisenda Miro
Antibiotics 2021, 10(4), 354; https://doi.org/10.3390/antibiotics10040354 - 28 Mar 2021
Cited by 6 | Viewed by 2435
Abstract
Some Aeromonas species, potentially pathogenic for humans, are known to express up to three different classes of chromosomal β-lactamases, which may become hyperproduced and cause treatment failure. The aim of this study was to assess the utility of these species-specific β-lactamase genes as [...] Read more.
Some Aeromonas species, potentially pathogenic for humans, are known to express up to three different classes of chromosomal β-lactamases, which may become hyperproduced and cause treatment failure. The aim of this study was to assess the utility of these species-specific β-lactamase genes as phylogenetic markers using whole-genome sequencing data. Core-genome alignments were generated for 36 Aeromonas genomes from seven different species and scanned for antimicrobial resistance genes. Core-genome alignment confirmed the MALDI-TOF identification of most of the isolates and re-identified an A. hydrophila isolate as A. dhakensis. Three (B, C and D) of the four Ambler classes of β-lactamase genes were found in A. sobria, A. allosacharophila, A. hydrophila and A. dhakensis (blaCphA, blaAmpC and blaOXA). A. veronii only showed class-B- and class-D-like matches (blaCphA and blaOXA), whereas those for A. media, A. rivipollensis and A. caviae were class C and D (blaCMY, blaMOX and blaOXA427). The phylogenetic tree derived from concatenated sequences of β-lactamase genes successfully clustered each species. Some isolates also had resistance to sulfonamides, quinolones and aminoglycosides. Whole-genome sequencing proved to be a useful method to identify Aeromonas at the species level, which led to the unexpected identification of A. dhakensis and A.rivipollensis and revealed the resistome of each isolate. Full article
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12 pages, 599 KiB  
Article
Antimicrobial Resistance Genes and Diversity of Clones among ESBL- and Acquired AmpC-Producing Escherichia coli Isolated from Fecal Samples of Healthy and Sick Cats in Portugal
by Isabel Carvalho, Nadia Safia Chenouf, Rita Cunha, Carla Martins, Paulo Pimenta, Ana Raquel Pereira, Sandra Martínez-Álvarez, Sónia Ramos, Vanessa Silva, Gilberto Igrejas, Carmen Torres and Patrícia Poeta
Antibiotics 2021, 10(3), 262; https://doi.org/10.3390/antibiotics10030262 - 05 Mar 2021
Cited by 14 | Viewed by 2715
Abstract
The aim of the study was to analyze the mechanisms of resistance in extended-spectrum beta-lactamase (ESBL)- and acquired AmpC (qAmpC)-producing Escherichia coli isolates from healthy and sick cats in Portugal. A total of 141 rectal swabs recovered from 98 sick and 43 healthy [...] Read more.
The aim of the study was to analyze the mechanisms of resistance in extended-spectrum beta-lactamase (ESBL)- and acquired AmpC (qAmpC)-producing Escherichia coli isolates from healthy and sick cats in Portugal. A total of 141 rectal swabs recovered from 98 sick and 43 healthy cats were processed for cefotaxime-resistant (CTXR) E. coli recovery (in MacConkey agar supplemented with 2 µg/mL cefotaxime). The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method was used for E. coli identification and antimicrobial susceptibility was performed by a disk diffusion test. The presence of resistance/virulence genes was tested by PCR sequencing. The phylogenetic typing and multilocus sequence typing (MLST) were determined by specific PCR sequencing. CTXRE. coli isolates were detected in seven sick and six healthy cats (7.1% and 13.9%, respectively). Based on the synergy tests, 11 of 13 CTXRE. coli isolates (one/sample) were ESBL-producers (ESBL total rate: 7.8%) carrying the following ESBL genes: blaCTX-M-1 (n = 3), blaCTX-M-15 (n = 3), blaCTX-M-55 (n = 2), blaCTX-M-27 (n = 2) and blaCTX-M-9 (n = 1). Six different sequence types were identified among ESBL-producers (sequence type/associated ESBLs): ST847/CTX-M-9, CTX-M-27, CTX-M-1; ST10/CTX-M-15, CTX-M-27; ST6448/CTX-M-15, CTX-M-55; ST429/CTX-M-15; ST101/CTX-M-1 and ST40/CTX-M-1. Three of the CTXR isolates were CMY-2-producers (qAmpC rate: 2.1%); two of them were ESBL-positive and one ESBL-negative. These isolates were typed as ST429 and ST6448 and were obtained in healthy or sick cats. The phylogenetic groups A/B1/D/clade 1 were detected among ESBL- and qAmpC-producing isolates. Cats are carriers of qAmpC (CMY-2)- and ESBL-producing E. coli isolates (mostly of variants of CTX-M group 1) of diverse clonal lineages, which might represent a public health problem due to the proximity of cats with humans regarding a One Health perspective. Full article
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18 pages, 2122 KiB  
Article
Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli
by Michael Pietsch, Yvonne Pfeifer, Stephan Fuchs and Guido Werner
Antibiotics 2021, 10(1), 90; https://doi.org/10.3390/antibiotics10010090 - 19 Jan 2021
Cited by 7 | Viewed by 2432
Abstract
(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, [...] Read more.
(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, we investigated fitness effects after a conjugative transfer of plasmids containing various beta-lactamase genes transferred into Escherichia coli. (2) Methods: Fourteen beta-lactamase-encoding plasmids were transferred from clinical donor strains to E. coli J53. Growth rates were compared for all transconjugants and the recipient. Selected transconjugants were challenged in long-term growth experiments. Growth rates were assessed at different time points during growth for 500 generations. Whole-genome sequencing (WGS) of initial and evolved transconjugants was determined. Results: Most plasmid acquisitions resulted in growth differences, ranging from −4.5% to 7.2%. Transfer of a single blaCMY-16-carrying plasmid resulted in a growth burden and a growth benefit in independent mating. Long-term growth led to a compensation of fitness burdens and benefits. Analyzing WGS revealed genomic changes caused by Single Nucleotide Polymorphisms (SNPs) and insertion sequences over time. Conclusions: Fitness effects associated with plasmid acquisitions were variable. Potential compensatory mutations identified in transconjugants’ genomes after 500 generations give interesting insights into aspects of plasmid–host adaptations. Full article
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