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Open AccessArticle

In Vitro Activity of Cefiderocol on Multiresistant Bacterial Strains and Genomic Analysis of Two Cefiderocol Resistant Strains

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Maria Antonia De Francesco

Antibiotics 2023, 12(4), 785; https://doi.org/10.3390/antibiotics12040785 - 20 Apr 2023

Viewed by 658

Abstract

Cefiderocol is a new siderophore cephalosporin that is effective against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to evaluate the activity of this new antimicrobial agent against a collection of pathogens using broth microdilution assays and to analyze [...] Read more.

Cefiderocol is a new siderophore cephalosporin that is effective against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to evaluate the activity of this new antimicrobial agent against a collection of pathogens using broth microdilution assays and to analyze the possible mechanism of cefiderocol resistance in two resistant Klebsiella pneumoniae isolates. One hundred and ten isolates were tested, comprising 67 Enterobacterales, two Acinetobacter baumannii, one Achromobacter xylosoxidans, 33 Pseudomonas aeruginosa and seven Stenotrophomonas maltophilia. Cefiderocol showed good in vitro activity, with an MIC < 2 μg/mL, and was able to inhibit 94% of the tested isolates. We observed a resistance rate of 6%. The resistant isolates consisted of six Klebsiella pneumoniae and one Escherichia coli, leading to a resistance rate of 10.4% among the Enterobacterales. Whole-genome sequencing analysis was performed on two cefiderocol-resistant Klebsiella pneumoniae isolates to investigate the possible mutations responsible for the observed resistance. Both strains belonged to ST383 and harbored different resistant and virulence genes. The analysis of genes involved in iron uptake and transport showed the presence of different mutations located in fhuA, fepA, iutA, cirA, sitC, apbC, fepG, fepC, fetB, yicI, yicJ, and yicL. Furthermore, for the first time, to the best of our knowledge, we described two Klebsiella pneumoniae isolates that synthesize a truncated fecA protein due to the transition from G to A, leading to a premature stop codon in the amino acid position 569, and a TonB protein carrying a 4-amino acid insertion (PKPK) after Lysine 103. In conclusion, our data show that cefiderocol is an effective drug against multidrug-resistant Gram-negative bacteria. However, the higher resistance rate observed in Enterobacterales underlines the need for active surveillance to limit the spread of these pathogens and to avoid the risks associated with the emergence of resistance to new drugs. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessArticle

Insight into the Mechanisms of Carbapenem Resistance in Klebsiella pneumoniae: A Study on IS26 Integrons, Beta-Lactamases, Porin Modifications, and Plasmidome Analysis

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Antibiotics 2023, 12(4), 749; https://doi.org/10.3390/antibiotics12040749 - 13 Apr 2023

Viewed by 753

Abstract

The emergence of carbapenem-resistant Klebsiella pneumoniae poses a significant threat to public health. In this study, we aimed to investigate the distribution and genetic diversity of plasmids carrying beta-lactamase resistance determinants in a collection of carbapenem-resistant K. pneumoniae blood isolates. Blood isolates of [...] Read more.

The emergence of carbapenem-resistant Klebsiella pneumoniae poses a significant threat to public health. In this study, we aimed to investigate the distribution and genetic diversity of plasmids carrying beta-lactamase resistance determinants in a collection of carbapenem-resistant K. pneumoniae blood isolates. Blood isolates of carbapenem-resistant K. pneumoniae bacteremia were collected and identified. Whole-genome sequencing, assembly and analysis were performed for the prediction of antimicrobial resistance determinants. Plasmidome analysis was also performed. Our plasmidome analysis revealed two major plasmid groups, IncFII/IncR and IncC, as key players in the dissemination of carbapenem resistance among carbapenem-resistant K. pneumoniae. Notably, plasmids within the same group exhibited conservation of encapsulated genes, suggesting that these plasmid groups may serve as conservative carriers of carbapenem-resistant determinants. Additionally, we investigated the evolution and expansion of IS26 integrons in carbapenem-resistant K. pneumoniae isolates using long-read sequencing. Our findings revealed the evolution and expansion of IS26 structure, which may have contributed to the development of carbapenem resistance in these strains. Our findings indicate that IncC group plasmids are associated with the endemic occurrence of carbapenem-resistant K. pneumoniae, highlighting the need for targeted interventions to control its spread. Although our study focuses on the endemic presence of carbapenem-resistant K. pneumoniae, it is important to note that carbapenem-resistant K. pneumoniae is indeed a global problem, with cases reported in multiple regions worldwide. Further research is necessary to better understand the factors driving the worldwide dissemination of carbapenem-resistant K. pneumoniae and to develop effective strategies for its prevention and control. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessArticle

Building an International One Health Strain Level Database to Characterise the Epidemiology of AMR Threats: ESBL—AmpC Producing E. coli as An Example—Challenges and Perspectives

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Sara Perestrelo

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Ana Amaro

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Michael S. M. Brouwer

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Lurdes Clemente

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Ana Sofia Ribeiro Duarte

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Annemarie Kaesbohrer

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Renata Karpíšková

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Vicente Lopez-Chavarrias

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Antibiotics 2023, 12(3), 552; https://doi.org/10.3390/antibiotics12030552 - 10 Mar 2023

Viewed by 1392

Abstract

Antimicrobial resistance (AMR) is one of the top public health threats nowadays. Among the most important AMR pathogens, Escherichia coli resistant to extended spectrum cephalosporins (ESC-EC) is a perfect example of the One Health problem due to its global distribution in animal, human, [...] Read more.

Antimicrobial resistance (AMR) is one of the top public health threats nowadays. Among the most important AMR pathogens, Escherichia coli resistant to extended spectrum cephalosporins (ESC-EC) is a perfect example of the One Health problem due to its global distribution in animal, human, and environmental sources and its resistant phenotype, derived from the carriage of plasmid-borne extended-spectrum and AmpC β-lactamases, which limits the choice of effective antimicrobial therapies. The epidemiology of ESC-EC infection is complex as a result of the multiple possible sources involved in its transmission, and its study would require databases ideally comprising information from animal (livestock, companion, wildlife), human, and environmental sources. Here, we present the steps taken to assemble a database with phenotypic and genetic information on 10,763 ESC-EC isolates retrieved from multiple sources provided by 13 partners located in eight European countries, in the frame of the DiSCoVeR Joint Research project funded by the One Health European Joint Programme (OH-EJP), along with its strengths and limitations. This database represents a first step to help in the assessment of different geographical and temporal trends and transmission dynamics in animals and humans. The work performed highlights aspects that should be considered in future international efforts, such as the one presented here. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

Open AccessArticle

Clonal Lineages and Virulence Factors of Carbapenem Resistant E. coli in Alameda County, California, 2017–2019

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Antibiotics 2022, 11(12), 1794; https://doi.org/10.3390/antibiotics11121794 - 10 Dec 2022

Viewed by 718

Abstract

The prevalence of carbapenem-resistant Enterobacterales (CRE) has been increasing since the year 2000 and is considered a serious public health threat according to the Centers for Disease Control and Prevention. Limited studies have genotyped Carbapenem-resistant Escherichia coli using whole genome sequencing to characterize [...] Read more.

The prevalence of carbapenem-resistant Enterobacterales (CRE) has been increasing since the year 2000 and is considered a serious public health threat according to the Centers for Disease Control and Prevention. Limited studies have genotyped Carbapenem-resistant Escherichia coli using whole genome sequencing to characterize the most common lineages and resistance and virulence genes. The aim of this study was to characterize sequence data from carbapenem-resistant E. coli isolates (n = 82) collected longitudinally by the Alameda County Public Health Laboratory (ACPHL) between 2017 and 2019. E. coli genomes were screened for antibiotic resistance genes (ARGs) and extraintestinal pathogenic E. coli virulence factor genes (VFGs). The carbapenem-resistant E. coli lineages were diverse, with 24 distinct sequence types (STs) represented, including clinically important STs: ST131, ST69, ST95, and ST73. All Ambler classes of Carbapenemases were present, with NDM-5 being most the frequently detected. Nearly all isolates (90%) contained genes encoding resistance to third-generation cephalosporins; bla_CTX-M genes were most common. The number of virulence genes present within pandemic STs was significantly higher than the number in non-pandemic lineages (p = 0.035). Virulence genes fimA (92%), trat (71%), kpsM (54%), and iutA (46%) were the most prevalent within the isolates. Considering the public health risk associated with CRE, these data enhance our understanding of the diversity of clinically important E. coli that are circulating in Alameda County, California. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessArticle

Clonal Dissemination of Extended-Spectrum Cephalosporin-Resistant Enterobacterales between Dogs and Humans in Households and Animal Shelters of Romania

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Andreea Paula Cozma

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Cristina Mihaela Rimbu

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Flavia Zendri

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Iuliana Elena Maciuca

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Dorina Timofte

Antibiotics 2022, 11(9), 1242; https://doi.org/10.3390/antibiotics11091242 - 13 Sep 2022

Cited by 3 | Viewed by 941

Abstract

Faecal carriage of extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales in healthy pets is a concerning issue. This study aimed to determine the prevalence, genetic background, and potential for interspecies transmission of these bacteria between dogs and humans within the same household (HH) or shelter environment [...] Read more.

Faecal carriage of extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales in healthy pets is a concerning issue. This study aimed to determine the prevalence, genetic background, and potential for interspecies transmission of these bacteria between dogs and humans within the same household (HH) or shelter environment in Romania. Faecal samples (n = 263) collected from healthy dogs (n = 102), their owners (n = 32), as well as dogs (n = 110) and staff (n = 19) from dog shelters, were screened for ESC-R carriage. Clonal relatedness of canine and human Escherichia coli isolates was established using Fourier Transform Infrared Spectroscopy (FTIR), followed by Illumina WGS of selected isolates. The highest prevalence of ESC-R Enterobacterales faecal carriage was identified in staff working at dog shelters (78.9%), followed by dogs from households (44.11%), dog owners (43.7%), and dogs from shelters (27%). FTIR identified 15 clusters of closely related E. coli isolates, including dog and human isolates from the same environment. Co-carriage of ESC-R isolates in both the dog and owner was identified in 12 HHs (37.5%), with two HHs (6%) having both the owner and dog carrying isolates with identical FTIR spectra, phylogroup, resistance genes, and Inc plasmids. Major ExPEC lineages such as ST127, ST10, ST155, and ST88 were detected in human and dog isolates. Our study revealed a high prevalence of faecal ESC-R E. coli carriage in both dogs and humans from Romanian households and shelters, where bidirectional clonal transmission between humans and dogs is likely. Furthermore, we identified ESC-R Enterobacterales co-carriage in people and dogs sharing the same environment using FTIR, demonstrating its value in AMR surveillance for humans and animals. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessArticle

Distribution and Genomic Characterization of Third-Generation Cephalosporin-Resistant Escherichia coli Isolated from a Single Family and Home Environment: A 2-Year Longitudinal Study

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Antibiotics 2022, 11(9), 1152; https://doi.org/10.3390/antibiotics11091152 - 25 Aug 2022

Viewed by 1261

Abstract

Third-generation cephalosporin-resistant Escherichia coli (CREC), particularly strains producing extended-spectrum β-lactamases (ESBLs), are a global concern. Our study aims to longitudinally assemble the genomic characteristics of CREC isolates from fecal samples from an index patient with recurrent CREC-related urinary tract infections and his family [...] Read more.

Third-generation cephalosporin-resistant Escherichia coli (CREC), particularly strains producing extended-spectrum β-lactamases (ESBLs), are a global concern. Our study aims to longitudinally assemble the genomic characteristics of CREC isolates from fecal samples from an index patient with recurrent CREC-related urinary tract infections and his family and swabs from his home environment 12 times between 2019 and 2021 to investigate the distribution of antibiotic resistance genes. CREC identified using the VITEK 2 were subjected to nanopore whole-genome sequencing (WGS). The WGS of 27 CREC isolates discovered in 137 specimens (1 urine, 123 feces, and 13 environmental) revealed the predominance of ST101 and ST131. Among these sequence types, bla_CTX-M (44.4%, n = 12) was the predominant ESBL gene family, with bla_CTX-M-14 (n = 6) being the most common. The remaining 15 (55.6%) isolates harbored bla_CMY-2 genes and were clonally diverse. All E. coli isolated from the index patient’s initial urine and fecal samples belonged to O25b:H4-B2-ST131 and carried bla_CTX-M-14. The results of sequence analysis indicate plasmid-mediated household transmission of bla_CMY-2 or bla_CTX-M-55. A strong genomic similarity was discovered between fecal ESBL-producing E. coli and uropathogenic strains. Furthermore, bla_CMY-2 genes were widely distributed among the CREC isolated from family members and their home environment. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessCommunication

Highly Virulent and Multidrug-Resistant Escherichia coli Sequence Type 58 from a Sausage in Germany

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Timo Homeier-Bachmann

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Katharina Schaufler

Antibiotics 2022, 11(8), 1006; https://doi.org/10.3390/antibiotics11081006 - 26 Jul 2022

Cited by 3 | Viewed by 1359

Abstract

Studies have previously described the occurrence of multidrug-resistant (MDR) Escherichia coli in human and veterinary medical settings, livestock, and, to a lesser extent, in the environment and food. While they mostly analyzed foodborne E. coli regarding phenotypic and sometimes genotypic antibiotic [...] Read more.

Studies have previously described the occurrence of multidrug-resistant (MDR) Escherichia coli in human and veterinary medical settings, livestock, and, to a lesser extent, in the environment and food. While they mostly analyzed foodborne E. coli regarding phenotypic and sometimes genotypic antibiotic resistance and basic phylogenetic classification, we have limited understanding of the in vitro and in vivo virulence characteristics and global phylogenetic contexts of these bacteria. Here, we investigated in-depth an E. coli strain (PBIO3502) isolated from a pork sausage in Germany in 2021. Whole-genome sequence analysis revealed sequence type (ST)58, which has an internationally emerging high-risk clonal lineage. In addition to its MDR phenotype that mostly matched the genotype, PBIO3502 demonstrated pronounced virulence features, including in vitro biofilm formation, siderophore secretion, serum resilience, and in vivo mortality in Galleria mellonella larvae. Along with the genomic analysis indicating close phylogenetic relatedness of our strain with publicly available, clinically relevant representatives of the same ST, these results suggest the zoonotic and pathogenic character of PBIO3502 with the potential to cause infection in humans and animals. Additionally, our study highlights the necessity of the One Health approach while integrating human, animal, and environmental health, as well as the role of meat products and food chains in the putative transmission of MDR pathogens. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessArticle

Distribution of ESBL/AmpC-Escherichia coli on a Dairy Farm

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Timo Homeier-Bachmann

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Jette F. Kleist

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Anne K. Schütz

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Lisa Bachmann

Antibiotics 2022, 11(7), 940; https://doi.org/10.3390/antibiotics11070940 - 13 Jul 2022

Cited by 1 | Viewed by 1072

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The aim of the study was to determine the prevalence of ESBL/AmpC-producing Escherichia (E.) coli and to investigate their on-farm distribution on an exemplary dairy farm. For this purpose, sample sizes were calculated, and fecal samples were collected from cattle of [...] Read more.

The aim of the study was to determine the prevalence of ESBL/AmpC-producing Escherichia (E.) coli and to investigate their on-farm distribution on an exemplary dairy farm. For this purpose, sample sizes were calculated, and fecal samples were collected from cattle of all ages and analyzed for the presence of ESBL/AmpC-E. coli using selective media supplemented with cefotaxime. These antibiotic-resistant bacteria were detected in 22.5% of the samples tested. The prevalence was highest in the calf age group, in which 100% of the collected fecal samples were positive. With increasing age, the prevalence decreased in the other sample groups. While ESBL/AmpC E. coli could still be detected in young stock (15%) and breeding heifers (5%), no resistant pathogens could be detected in adult animals. Whole-genome sequencing of the ESBL/AmpC-E. coli isolates revealed, first, that all isolates were ESBL producers (CTX-M-1 and CTX-M-15) and, second, that ST362, which is known as a biofilm producer, was dominant in the calves (85%, n = 17). Based on these results and the evaluation of a questionnaire, possible causes for the occurrence of ESBL/AmpC-E. coli were discussed and recommendations for the reduction in transmission were formulated. Unlike most German dairy farms, no waste milk feeding was apparent; therefore, factors reducing ESBL/AmpC-E. coli are primarily related to an improvement in hygiene management to prevent biofilms, e.g., in nipple buckets, but also to question the use of antibiotics, e.g., in the treatment of diarrheic calves. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

Open AccessArticle

TEM,CTX-M,SHV Genes in ESBL-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Clinical Samples in a County Clinical Emergency Hospital Romania-Predominance of CTX-M-15

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Alice Elena Ghenea

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Ovidiu Mircea Zlatian

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Oana Mariana Cristea

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Anca Ungureanu

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Radu Razvan Mititelu

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Andrei Theodor Balasoiu

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Anca-Loredana Udriștoiu

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Maria Balasoiu

Antibiotics 2022, 11(4), 503; https://doi.org/10.3390/antibiotics11040503 - 10 Apr 2022

Cited by 6 | Viewed by 3093

Abstract

Background: CTX-M betalactamases have shown a rapid spread in the recent years among Enterobacteriaceae and have become the most prevalent Extended Spectrum Beta-Lactamases (ESBLs) in many parts of the world. The introduction and dissemination of antibiotic-resistant genes limits options for treatment, increases mortality [...] Read more.

Background: CTX-M betalactamases have shown a rapid spread in the recent years among Enterobacteriaceae and have become the most prevalent Extended Spectrum Beta-Lactamases (ESBLs) in many parts of the world. The introduction and dissemination of antibiotic-resistant genes limits options for treatment, increases mortality and morbidity in patients, and leads to longer hospitalization and expensive costs. We aimed to identify the beta-lactamases circulating encoded by the genes bla_CTX-M-15, bla_SHV-1 and bla_TEM-1 in Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) strains. Furthermore, we established the associated resistance phenotypes among patients hospitalized in the Intensive Care Unit (ICU) from County Clinical Emergency Hospital of Craiova, Romania. Methods: A total of 46 non-duplicated bacterial strains (14 strains of E. coli and 32 strains of K. pneumoniae), which were resistant to ceftazidime (CAZ) and cefotaxime (CTX) by Kirby–Bauer disk diffusion method, were identified using the automated VITEK2 system. Detection of ESBL-encoding genes and other resistance genes was carried out by PCR. Results. E. coli strains were resistant to 3rd generation cephalosporins and moderately resistant to quinolones, whereas K. pneumoniae strains were resistant to penicillins, cephalosporins, and sulfamides, and moderately resistant to quinolones and carbapenems. Most E. coli strains harbored bla_CTX-M-15 gene (13/14 strains), a single strain had the bla_SHV-1 gene, but 11 strains harbored bla_TEM-1 gene. The mcr-1 gene was not detected. We detected tet(A) gene in six strains and tet(B) in one strain. In K. pneumoniae strains we detected bla_CTX-M-15 in 23 strains, bla_SHV-₁ in all strains and bla_TEM-1 in 14 strains. The colistin resistance gene mcr-1 was not detected. The tetracycline gene tet(A) was detected in 11 strains, but the gene tet(B) was not detected in any strains. Conclusions. The development in antibiotic resistance highlights the importance of establishing policies to reduce antibiotic use and improving the national resistance surveillance system in order to create local antibiotic therapy guidelines. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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Open AccessReview

Extended-Spectrum β-Lactamases (ESBL) Producing Bacteria in Animals

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Chien-Hao Tseng

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Chia-Wei Liu

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Po-Yu Liu

Antibiotics 2023, 12(4), 661; https://doi.org/10.3390/antibiotics12040661 - 28 Mar 2023

Viewed by 850

Abstract

Animals have been identified as potential reservoirs and vectors of resistance genes, with studies showing that Gram-negative bacteria can acquire resistance through the horizontal transmission of resistance genes on plasmids. It is important to understand the distribution of antimicrobial-resistant bacteria and their drug-resistant [...] Read more.

Animals have been identified as potential reservoirs and vectors of resistance genes, with studies showing that Gram-negative bacteria can acquire resistance through the horizontal transmission of resistance genes on plasmids. It is important to understand the distribution of antimicrobial-resistant bacteria and their drug-resistant genes in animals. Previous review articles mostly focused on a single bacterium or a single animal. Our objective is to compile all ESBL-producing bacteria isolated from various animals in recent years and provide a comprehensive viewpoint. Using a thorough PubMed literature search spanning from 1 January 2020 to 30 June 2022, studies exploring extended-spectrum beta-lactamase (ESBL) producing bacteria in animals were included. ESBL-producing bacteria are present in animals from various countries around the world. The most common sources of these bacteria were farm animals, and the most frequently isolated bacteria were Escherichia coli and Klebsiella pneumoniae. The most detected ESBL genes were bla_TEM, bla_SHV, and bla_CTX-M. The presence of ESBL-producing bacteria in animals highlights the importance of the One Health approach to address the issue of antibiotic resistance. Further research is needed to better understand the epidemiology and mechanisms of the spread of ESBL-producing bacteria in animal populations and their potential impact on human and animal health. Full article

(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)

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