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14 pages, 635 KiB

Open AccessArticle

Genetic Characterization of Carbapenem-Resistant Klebsiella spp. from Municipal and Slaughterhouse Wastewater

by Mykhailo Savin, Gabriele Bierbaum, Nico T. Mutters, Ricarda Maria Schmithausen, Judith Kreyenschmidt, Isidro García-Meniño, Silvia Schmoger, Annemarie Käsbohrer and Jens Andre Hammerl

Antibiotics 2022, 11(4), 435; https://doi.org/10.3390/antibiotics11040435 - 24 Mar 2022

Cited by 14 | Viewed by 3582

Abstract

Currently, human and veterinary medicine are threatened worldwide by an increasing resistance to carbapenems, particularly present in opportunistic Enterobacterales pathogens (e.g., Klebsiella spp.). However, there is a lack of comprehensive and comparable data on their occurrence in wastewater, as well as on the [...] Read more.

Currently, human and veterinary medicine are threatened worldwide by an increasing resistance to carbapenems, particularly present in opportunistic Enterobacterales pathogens (e.g., Klebsiella spp.). However, there is a lack of comprehensive and comparable data on their occurrence in wastewater, as well as on the phenotypic and genotypic characteristics for various countries including Germany. Thus, this study aims to characterize carbapenem-resistant Klebsiella spp. isolated from municipal wastewater treatment plants (mWWTPs) and their receiving water bodies, as well as from wastewater and process waters from poultry and pig slaughterhouses. After isolation using selective media and determination of carbapenem (i.e., ertapenem) resistance using broth microdilution to apply epidemiological breakpoints, the selected isolates (n = 30) were subjected to WGS. The vast majority of the isolates (80.0%) originated from the mWWTPs and their receiving water bodies. In addition to ertapenem, Klebsiella spp. isolates exhibited resistance to meropenem (40.0%) and imipenem (16.7%), as well as to piperacillin-tazobactam (50.0%) and ceftolozan-tazobactam (50.0%). A high diversity of antibiotic-resistance genes (n = 68), in particular those encoding β-lactamases, was revealed. However, with the exception of bla_GES-5-like, no acquired carbapenemase-resistance genes were detected. Virulence factors such as siderophores (e.g., enterobactin) and fimbriae type 1 were present in almost all isolates. A wide genetic diversity was indicated by assigning 66.7% of the isolates to 12 different sequence types (STs), including clinically relevant ones (e.g., ST16, ST252, ST219, ST268, ST307, ST789, ST873, and ST2459). Our study provides information on the occurrence of carbapenem-resistant, ESBL-producing Klebsiella spp., which is of clinical importance in wastewater and surface water in Germany. These findings indicate their possible dissemination in the environment and the potential risk of colonization and/or infection of humans, livestock and wildlife associated with exposure to contaminated water sources. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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21 pages, 1249 KiB

Open AccessArticle

Prevalence and Molecular Typing of Carbapenemase-Producing Enterobacterales among Newborn Patients in Italy

by Marilena Agosta, Daniela Bencardino, Marta Argentieri, Laura Pansani, Annamaria Sisto, Marta Luisa Ciofi Degli Atti, Carmen D’Amore, Lorenza Putignani, Pietro Bagolan, Barbara Daniela Iacobelli, Andrea Dotta, Ludovica Martini, Luca Di Chiara, Mauro Magnani, Carlo Federico Perno, Francesca Andreoni and Paola Bernaschi

Antibiotics 2022, 11(4), 431; https://doi.org/10.3390/antibiotics11040431 - 23 Mar 2022

Cited by 5 | Viewed by 3136

Abstract

The spread of carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), is a serious public health threat in pediatric hospitals. The associated risk in newborns is due to their underdeveloped immune system and limited [...] Read more.

The spread of carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), is a serious public health threat in pediatric hospitals. The associated risk in newborns is due to their underdeveloped immune system and limited treatment options. The aim was to estimate the prevalence and circulation of CPE among the neonatal intensive units of a major pediatric hospital in Italy and to investigate their molecular features. A total of 124 CPE were isolated from rectal swabs of 99 newborn patients at Bambino Gesù Children’s Hospital between July 2016 and December 2019. All strains were characterized by antimicrobial susceptibility testing, detection of resistance genes, and PCR-based replicon typing (PBRT). One strain for each PBRT profile of K. pneumoniae or E. coli was characterized by multilocus-sequence typing (MLST). Interestingly, the majority of strains were multidrug-resistant and carried the bla_NDM gene. A large part was characterized by a multireplicon status, and FII, A/C, FIA (15%) was the predominant. Despite the limited size of collection, MLST analysis revealed a high number of Sequence Types (STs): 14 STs among 28 K. pneumoniae and 8 STs among 11 E. coli, with the prevalence of the well-known clones ST307 and ST131, respectively. This issue indicated that some strains shared the same circulating clone. We identified a novel, so far never described, ST named ST10555, found in one E. coli strain. Our investigation showed a high heterogeneity of CPE circulating among neonatal units, confirming the need to monitor their dissemination in the hospital also through molecular methods. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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18 pages, 1167 KiB

Open AccessArticle

Comparison of Six Phenotypic Assays with Reference Methods for Assessing Colistin Resistance in Clinical Isolates of Carbapenemase-Producing Enterobacterales: Challenges and Opportunities

by Annamária Főldes, Edit Székely, Septimiu Toader Voidăzan and Minodora Dobreanu

Antibiotics 2022, 11(3), 377; https://doi.org/10.3390/antibiotics11030377 - 11 Mar 2022

Cited by 8 | Viewed by 3096

Abstract

The global escalation of severe infections due to carbapenemase-producing Enterobacterales (CPE) isolates has prompted increased usage of parenteral colistin. Considering the reported difficulties in assessing their susceptibility to colistin, the purpose of the study was to perform a comparative evaluation of six phenotypic [...] Read more.

The global escalation of severe infections due to carbapenemase-producing Enterobacterales (CPE) isolates has prompted increased usage of parenteral colistin. Considering the reported difficulties in assessing their susceptibility to colistin, the purpose of the study was to perform a comparative evaluation of six phenotypic assays—the colistin broth disc elution (CBDE), Vitek 2 Compact (bioMérieux SA, Marcy l’Etoile, France), the Micronaut MIC-Strip Colistin (Merlin Diagnostika GMBH, Bornheim-Hensel, Germany), the gradient diffusion strip Etest (bioMérieux SA, Marcy l’Etoile, France), ChromID Colistin R Agar (COLR) (bioMérieux SA, Marcy l’Etoile, France), and the Rapid Polymyxin NP Test (ELITechGroup, Signes, France)—versus the reference method of broth microdilution (BMD). All false resistance results were further assessed using population analysis profiling (PAP). Ninety-two nonrepetitive clinical CPE strains collected from two hospitals were evaluated. The BMD confirmed 36 (39.13%) isolates susceptible to colistin. According to the BMD, the Micronaut MIC-Strip Colistin, the CBDE, and the COLR medium exhibited category agreement (CA) of 100%. In comparison with the BMD, the highest very major discrepancy (VMD) was noted for Etest (n = 15), and the only false resistance results were recorded for the Rapid Polymyxin NP Test (n = 3). Only the PAP method and the Rapid Polymyxin NP Test were able to detect heteroresistant isolates (n = 2). Thus, there is an urgent need to further optimize the diagnosis strategies for colistin resistance. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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14 pages, 1332 KiB

Open AccessArticle

Persistence and Dissemination Capacities of a bla_NDM-5-Harboring IncX-3 Plasmid in Escherichia coli Isolated from an Urban River in Montpellier, France

by Florence Hammer-Dedet, Fabien Aujoulat, Estelle Jumas-Bilak and Patricia Licznar-Fajardo

Antibiotics 2022, 11(2), 196; https://doi.org/10.3390/antibiotics11020196 - 2 Feb 2022

Cited by 6 | Viewed by 2113

Abstract

To investigate the capacities of persistence and dissemination of bla_NDM-5 within Escherichia coli and in aquatic environment, we characterized E. coli (sequence type 636) strains B26 and B28 isolated one month apart from the same urban river in Montpellier, France. The two [...] Read more.

To investigate the capacities of persistence and dissemination of bla_NDM-5 within Escherichia coli and in aquatic environment, we characterized E. coli (sequence type 636) strains B26 and B28 isolated one month apart from the same urban river in Montpellier, France. The two isolates carried a pTsB26 plasmid, which sized 45,495 Kb, harbored bla_NDM-5 gene and belonged to IncX-3 incompatibility group. pTsB26 was conjugative in vitro at high frequency, it was highly stable after 400 generations and it exerted no fitness cost on its host. bla_NDM-5harboring plasmids are widely dispersed in E. coli all around the world, with no lineage specialization. The genomic comparison between B26 and B28 stated that the two isolates probably originated from the same clone, suggesting the persistence of pTsB26 in an E. coli host in aquatic environment. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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21 pages, 1803 KiB

Open AccessArticle

Polyclonal Endemicity of Carbapenemase-Producing Klebsiella pneumoniae in ICUs of a Greek Tertiary Care Hospital

by Efthymia Protonotariou, Georgios Meletis, Dimitrios Pilalas, Paraskevi Mantzana, Areti Tychala, Charalampos Kotzamanidis, Dimitra Papadopoulou, Theofilos Papadopoulos, Michalis Polemis, Simeon Metallidis and Lemonia Skoura

Antibiotics 2022, 11(2), 149; https://doi.org/10.3390/antibiotics11020149 - 25 Jan 2022

Cited by 15 | Viewed by 3031

Abstract

Carbapenemase-producing Klebsiella pneumoniae (CPKP) emerged in Greece in 2002 and became endemic thereafter. Driven by a notable variability in the phenotypic testing results for carbapenemase production in K. pneumoniae isolates from the intensive care units (ICUs) of our hospital, we performed a study [...] Read more.

Carbapenemase-producing Klebsiella pneumoniae (CPKP) emerged in Greece in 2002 and became endemic thereafter. Driven by a notable variability in the phenotypic testing results for carbapenemase production in K. pneumoniae isolates from the intensive care units (ICUs) of our hospital, we performed a study to assess the molecular epidemiology of CPKP isolated between 2016 and 2019 using pulse-field gel electrophoresis (PFGE) including isolates recovered from 165 single patients. We investigated the molecular relatedness among strains recovered from rectal surveillance cultures and from respective subsequent infections due to CPKP in the same individual (48/165 cases). For the optimal interpretation of our findings, we carried out a systematic review regarding the clonality of CPKP isolated from clinical samples in ICUs in Europe. In our study, we identified 128 distinguishable pulsotypes and 17 clusters that indicated extended dissemination of CPKP within the hospital ICU setting throughout the study period. Among the clinical isolates, 122 harbored KPC genes (74%), 2 harbored KPC+NDM (1.2%), 38 harbored NDM (23%), 1 harbored NDM+OXA-48 (0.6%), 1 harbored NDM+VIM (0.6%) and 1 harbored the VIM (0.6%) gene. Multiple CPKP strains in our hospital have achieved sustained transmission. The polyclonal endemicity of CPKP presents a further threat for the selection of pathogens resistant to last-resort antimicrobial agents. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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9 pages, 236 KiB

Open AccessArticle

The Evaluation of Eazyplex^® SuperBug CRE Assay Usefulness for the Detection of ESBLs and Carbapenemases Genes Directly from Urine Samples and Positive Blood Cultures

by Alicja Sękowska and Tomasz Bogiel

Antibiotics 2022, 11(2), 138; https://doi.org/10.3390/antibiotics11020138 - 21 Jan 2022

Cited by 3 | Viewed by 2913

Abstract

Increasing antimicrobial resistance of Gram-negative rods is an important diagnostic, clinical and epidemiological problem of modern medicine. Therefore, it is important to detect multi-drug resistant strains as early on as possible. This study aimed to evaluate Eazyplex^® SuperBug CRE assay usefulness for [...] Read more.

Increasing antimicrobial resistance of Gram-negative rods is an important diagnostic, clinical and epidemiological problem of modern medicine. Therefore, it is important to detect multi-drug resistant strains as early on as possible. This study aimed to evaluate Eazyplex^® SuperBug CRE assay usefulness for beta-lactamase gene detection among Gram-negative rods, directly from urine samples and positive blood cultures. The Eazyplex^® SuperBug CRE assay is based on a loop-mediated isothermal amplification of genetic material and allows for the detection of a selection of genes encoding carbapenemases, KPC, NDM, VIM, OXA-48, OXA-181 and extended-spectrum beta-lactamases from the CTX-M-1 and CTX-M-9 groups. A total of 120 clinical specimens were included in the study. The test gave valid results for 58 (96.7%) urine samples and 57 (95.0%) positive blood cultures. ESBL and/or carbapenemase enzymes genes were detected in 56 (93.3%) urine and 55 (91.7%) blood samples, respectively. The Eazyplex^® SuperBug CRE assay can be used for a rapid detection of the genes encoding the most important resistance mechanisms to beta-lactams in Gram-negative rods also without the necessity of bacterial culture. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

12 pages, 944 KiB

Open AccessArticle

NDM-1 Introduction in Portugal through a ST11 KL105 Klebsiella pneumoniae Widespread in Europe

by Ângela Novais, Rita Veiga Ferraz, Mariana Viana, Paula Martins da Costa and Luísa Peixe

Antibiotics 2022, 11(1), 92; https://doi.org/10.3390/antibiotics11010092 - 12 Jan 2022

Cited by 15 | Viewed by 2745

Abstract

The changing epidemiology of carbapenem-resistant Klebsiella pneumoniae in Southern European countries is challenging for infection control, and it is critical to identify and track new genetic entities (genes, carbapenemases, clones) quickly and with high precision. We aimed to characterize the strain responsible for [...] Read more.

The changing epidemiology of carbapenem-resistant Klebsiella pneumoniae in Southern European countries is challenging for infection control, and it is critical to identify and track new genetic entities (genes, carbapenemases, clones) quickly and with high precision. We aimed to characterize the strain responsible for the first recognized outbreak by an NDM-1-producing K. pneumoniae in Portugal, and to elucidate its diffusion in an international context. NDM-1-producing multidrug-resistant K. pneumoniae isolates from hospitalized patients (2018–2019) were characterized using FTIR spectroscopy, molecular typing, whole-genome sequencing, and comparative genomics with available K. pneumoniae ST11 KL105 genomes. FT-IR spectroscopy allowed the rapid (ca. 4 h after incubation) identification of the outbreak strains as ST11 KL105, supporting outbreak control. Epidemiological information supports a community source but without linkage to endemic regions of NDM-1 producers. Whole-genome comparison with previous DHA-1-producing ST11 KL105 strains revealed the presence of different plasmid types and antibiotic resistance traits, suggesting the entry of a new strain. In fact, this ST11 KL105 clade has successfully disseminated in Europe with variable beta-lactamases, but essentially as ESBL or DHA-1 producers. We expand the distribution map of NDM-1-producing K. pneumoniae in Europe, at the expense of a successfully established ST11 KL105 K. pneumoniae clade circulating with variable plasmid backgrounds and beta-lactamases. Our work further supports the use of FT-IR as an asset to support quick infection control. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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11 pages, 1368 KiB

Open AccessArticle

The Antimicrobial Resistance Characteristics of Imipenem-Non-Susceptible, Imipenemase-6-Producing Escherichia coli

by Reo Onishi, Katsumi Shigemura, Kayo Osawa, Young-Min Yang, Koki Maeda, Shiuh-Bin Fang, Shian-Ying Sung, Kenichiro Onuma, Atsushi Uda, Takayuki Miyara and Masato Fujisawa

Antibiotics 2022, 11(1), 32; https://doi.org/10.3390/antibiotics11010032 - 28 Dec 2021

Cited by 4 | Viewed by 3546

Abstract

Imipenemase-6 (IMP-6) type carbapenemase-producing Enterobacteriaceae is regarded as dangerous due to its unique lack of antimicrobial susceptibility. It is resistant to meropenem (MEPM) but susceptible to imipenem (IPM). In addition to carbapenemase, outer membrane porins and efflux pumps also play roles in carbapenem [...] Read more.

Imipenemase-6 (IMP-6) type carbapenemase-producing Enterobacteriaceae is regarded as dangerous due to its unique lack of antimicrobial susceptibility. It is resistant to meropenem (MEPM) but susceptible to imipenem (IPM). In addition to carbapenemase, outer membrane porins and efflux pumps also play roles in carbapenem resistance by reducing the antimicrobial concentration inside cells. Extended-spectrum β-lactamase (ESBL) is transmitted with IMP-6 by the plasmid and broadens the spectrum of antimicrobial resistance. We collected 42 strains of IMP-6-producing Escherichia coli and conducted a molecular analysis of carbapenemase, ESBL, porin, efflux, and epidemiological characteristics using plasmid replicon typing. Among the 42 isolates, 21 strains were susceptible to IPM (50.0%) and 1 (2.4%) to MEPM. Seventeen strains (40.5%) co-produced CTX-M-2 type ESBL. We found that the relative expression of ompC and ompF significantly correlated with the MIC of IPM (p = 0.01 and p = 0.03, respectively). Sixty-eight% of CTX-M-2-non-producing strains had IncI1, which was significantly different from CTX-M-2-producing strains (p < 0.001). In conclusion, 50.0% of our IMP-6-producing strains were non-susceptible to IPM, which is different from the typical pattern and can be attributed to decreased porin expression. Further studies investigating other types of carbapenemase are warranted. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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10 pages, 931 KiB

Open AccessArticle

Infection Control for a Carbapenem-Resistant Enterobacteriaceae Outbreak in an Advanced Emergency Medical Services Center

by Yoshiro Sakai, Kenji Gotoh, Ryuichi Nakano, Jun Iwahashi, Miho Miura, Rie Horita, Naoki Miyamoto, Hisakazu Yano, Mikinori Kannae, Osamu Takasu and Hiroshi Watanabe

Antibiotics 2021, 10(12), 1537; https://doi.org/10.3390/antibiotics10121537 - 15 Dec 2021

Cited by 4 | Viewed by 2588

Abstract

Background: A carbapenem-resistant Enterobacteriaceae (CRE) outbreak occurred in an advanced emergency medical service center [hereafter referred to as the intensive care unit (ICU)] between 2016 and 2017. Aim: Our objective was to evaluate the infection control measures for CRE outbreaks. Methods: CRE strains [...] Read more.

Background: A carbapenem-resistant Enterobacteriaceae (CRE) outbreak occurred in an advanced emergency medical service center [hereafter referred to as the intensive care unit (ICU)] between 2016 and 2017. Aim: Our objective was to evaluate the infection control measures for CRE outbreaks. Methods: CRE strains were detected in 16 inpatients located at multiple sites. Environmental cultures were performed and CRE strains were detected in 3 of 38 sites tested. Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and detection of β-lactamase genes were performed against 25 CRE strains. Findings: Molecular typing showed the PFGE patterns of two of four Klebsiella pneumoniae strains were closely related and the same MLST (ST2388), and four of five Enterobacter cloacae strains were closely related and same MLST (ST252). Twenty-three of 25 CRE strains harbored the IMP-1 β-lactamase gene and 15 of 23 CRE strains possessed IncFIIA replicon regions. Despite interventions by the infection control team, new inpatients with the CRE strain continued to appear. Therefore, the ICU was partially closed and the inpatients with CRE were isolated, and the ICU staff was divided into two groups between inpatients with CRE and non-CRE strains to avoid cross-contamination. Although the occurrence of new cases dissipated quickly after the partial closure, a few months were required to eradicate the CRE outbreak. Conclusion: Our data suggest that the various and combined measures that were used for infection control were essential in stopping this CRE outbreak. In particular, partial closure to isolate the ICU and division of the ICU staff were effective. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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8 pages, 2398 KiB

Open AccessArticle

Complete Genome Sequences of Klebsiella michiganensis and Citrobacter farmeri, KPC-2-Producers Serially Isolated from a Single Patient

by Jehane Y. Abed, Maxime Déraspe, Ève Bérubé, Matthew D’Iorio, Ken Dewar, Maurice Boissinot, Jacques Corbeil, Michel G. Bergeron and Paul H. Roy

Antibiotics 2021, 10(11), 1408; https://doi.org/10.3390/antibiotics10111408 - 18 Nov 2021

Cited by 6 | Viewed by 2527

Abstract

Carbapenemase-producing Enterobacterales, including KPC-2 producers, have become a major clinical problem. During an outbreak in Quebec City, Canada, KPC-2-producing Klebsiella michiganensis and Citrobacter farmeri were isolated from a patient six weeks apart. We determined their complete genome sequences. Both isolates carried nearly identical [...] Read more.

Carbapenemase-producing Enterobacterales, including KPC-2 producers, have become a major clinical problem. During an outbreak in Quebec City, Canada, KPC-2-producing Klebsiella michiganensis and Citrobacter farmeri were isolated from a patient six weeks apart. We determined their complete genome sequences. Both isolates carried nearly identical IncN2 plasmids with blaKPC-2 on a Tn4401b element. Both strains also carried IncP1 plasmids, but that of C. farmeri did not carry a Beta-lactamase gene, whereas that of K. michiganensis carried a second copy of bla_KPC-2 on Tn4401b. These results suggest recent plasmid transfer between the two species and a recent transposition event. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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10 pages, 686 KiB

Open AccessArticle

Antimicrobial Activity of a Lipidated Temporin L Analogue against Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates

by Emanuela Roscetto, Rosa Bellavita, Rossella Paolillo, Francesco Merlino, Nicola Molfetta, Paolo Grieco, Elisabetta Buommino and Maria Rosaria Catania

Antibiotics 2021, 10(11), 1312; https://doi.org/10.3390/antibiotics10111312 - 28 Oct 2021

Cited by 17 | Viewed by 1895

Abstract

Over the years, the increasing acquisition of antibiotic resistance genes has led to the emergence of highly resistant bacterial strains and the loss of standard antibiotics’ efficacy, including β-lactam/β-lactamase inhibitor combinations and the last line carbapenems. Klebsiella pneumoniae is considered one of the [...] Read more.

Over the years, the increasing acquisition of antibiotic resistance genes has led to the emergence of highly resistant bacterial strains and the loss of standard antibiotics’ efficacy, including β-lactam/β-lactamase inhibitor combinations and the last line carbapenems. Klebsiella pneumoniae is considered one of the major exponents of a group of multidrug-resistant ESKAPE pathogens responsible for serious healthcare-associated infections. In this study, we proved the antimicrobial activity of two analogues of Temporin L against twenty carbapenemase-producing K. pneumoniae clinical isolates. According to the antibiotic susceptibility assay, all the K. pneumoniae strains were resistant to at least one other class of antibiotics, in addition to beta-lactams. Peptides 1B and C showed activity on all test strains, but the lipidated analogue C expressed the greater antimicrobial properties, with MIC values ranging from 6.25 to 25 µM. Furthermore, the peptide C showed bactericidal activity at MIC values. The results clearly highlight the great potential of antimicrobial peptides both as a new treatment option for difficult-to-treat infections and as a new strategy of drug-resistance control. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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10 pages, 4560 KiB

Open AccessArticle

High-Level Carbapenem Resistance among OXA-48-Producing Klebsiellapneumoniae with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility

by Pilar Lumbreras-Iglesias, María Rosario Rodicio, Pablo Valledor, Tomás Suárez-Zarracina and Javier Fernández

Antibiotics 2021, 10(10), 1174; https://doi.org/10.3390/antibiotics10101174 - 27 Sep 2021

Cited by 10 | Viewed by 2539

Abstract

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening [...] Read more.

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing K. pneumoniae with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing K. pneumoniae were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of ompK35 and ompK36 were performed in silico. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing K. pneumoniae isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in ompK35 were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing K. pneumoniae. OXA-48-producing K. pneumoniae with porin disruptions are a cause of concern; ceftazidime/avibactam showed good in vitro activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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14 pages, 305 KiB

Open AccessEditor’s ChoiceArticle

A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic

by Estefanía Cano-Martín, Inés Portillo-Calderón, Patricia Pérez-Palacios, José María Navarro-Marí, María Amelia Fernández-Sierra and José Gutiérrez-Fernández

Antibiotics 2021, 10(9), 1127; https://doi.org/10.3390/antibiotics10091127 - 18 Sep 2021

Cited by 9 | Viewed by 3412

Abstract

Bacterial resistance to antibiotics has proven difficult to control over the past few decades. The large group of multidrug-resistant bacteria includes carbapenemase-producing bacteria (CPB), for which limited therapeutic options and infection control measures are available. Furthermore, carbapenemases associate with high-risk clones that are [...] Read more.

Bacterial resistance to antibiotics has proven difficult to control over the past few decades. The large group of multidrug-resistant bacteria includes carbapenemase-producing bacteria (CPB), for which limited therapeutic options and infection control measures are available. Furthermore, carbapenemases associate with high-risk clones that are defined by the sequence type (ST) to which each bacterium belongs. The objectives of this cross-sectional and retrospective study were to describe the CPB population isolated in a third-level hospital in Southern Spain between 2015 and 2020 and to establish the relationship between the ST and the epidemiological situation defined by the hospital. CPB were microbiologically studied in all rectal and pharyngeal swabs and clinical samples received between January 2015 and December 2020, characterizing isolates using MicroScan and mass spectrometry. Carbapenemases were detected by PCR and Sanger sequencing, and STs were assigned by multilocus sequence typing (MLST). Isolates were genetically related by pulsed-field gel electrophoresis using Xbal, Spel, or Apal enzymes. The episodes in which each CPB was isolated were recorded and classified as involved or non-involved in an outbreak. There were 320 episodes with CPB during the study period: 18 with K. pneumoniae, 14 with Klebisella oxytoca, 9 with Citrobacter freundii, 11 with Escherichia coli, 46 with Enterobacter cloacae, 70 with Acinetobacter baumannii, and 52 with Pseudomonas aeruginosa. The carbapenemase groups detected were OXA, VIM, KPC, and NDM with various subgroups. Synchronous relationships were notified between episodes of K. pneumoniae and outbreaks for ST15, ST258, ST307, and ST45, but not for the other CPB. There was a major increase in infections with CPB over the years, most notably during 2020, coinciding with the COVID-19 pandemic. This study highlights the usefulness of gene sequencing techniques to control the spread of these microorganisms, especially in healthcare centers. These techniques offer faster results, and a reduction in their cost may make their real-time application more feasible. The combination of epidemiological data with real-time molecular sequencing techniques can provide a major advance in the transmission control of these CPB and in the management of infected patients. Real-time sequencing is essential to increase precision and thereby control outbreaks and target infection prevention measures in a more effective manner. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

10 pages, 578 KiB

Open AccessArticle

Whole-Genome Sequencing for Molecular Characterization of Carbapenem-Resistant Enterobacteriaceae Causing Lower Urinary Tract Infection among Pediatric Patients

by Hassan Al Mana, Sathyavathi Sundararaju, Clement K. M. Tsui, Andres Perez-Lopez, Hadi Yassine, Asmaa Al Thani, Khalid Al-Ansari and Nahla O. Eltai

Antibiotics 2021, 10(8), 972; https://doi.org/10.3390/antibiotics10080972 - 12 Aug 2021

Cited by 14 | Viewed by 3865

Abstract

Antibiotic resistance is a growing public health problem globally, incurring health and cost burdens. The occurrence of antibiotic-resistant bacterial infections has increased significantly over the years. Gram-negative bacteria display the broadest resistance range, with bacterial species expressing extended-spectrum β-lactamases (ESBLs), AmpC, and carbapenemases. [...] Read more.

Antibiotic resistance is a growing public health problem globally, incurring health and cost burdens. The occurrence of antibiotic-resistant bacterial infections has increased significantly over the years. Gram-negative bacteria display the broadest resistance range, with bacterial species expressing extended-spectrum β-lactamases (ESBLs), AmpC, and carbapenemases. All carbapenem-resistant Enterobacteriaceae (CRE) isolates from pediatric urinary tract infections (UTIs) between October 2015 and November 2019 (n = 30). All isolates underwent antimicrobial resistance phenotypic testing using the Phoenix NMIC/ID-5 panel, and carbapenemase production was confirmed using the NG-Test CARBA 5 assay. Whole-genome sequencing was performed on the CREs. The sequence type was identified using the Achtman multi-locus sequence typing scheme, and antimicrobial resistance markers were identified using ResFinder and the CARD database. The most common pathogens causing CRE UTIs were E. coli (63.3%) and K. pneumoniae (30%). The most common carbapenemases produced were OXA-48-like enzymes (46.6%) and NDM enzymes (40%). Additionally, one E. coli harbored IMP-26, and two K. pneumoniae possessed mutations in ompK37 and/or ompK36. Lastly, one E. coli had a mutation in the marA porin and efflux pump regulator. The findings highlight the difference in CRE epidemiology in the pediatric population compared to Qatar’s adult population, where NDM carbapenemases are more common. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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8 pages, 3446 KiB

Open AccessArticle

Molecular Detection of Carbapenemases in Enterobacterales: A Comparison of Real-Time Multiplex PCR and Whole-Genome Sequencing

by Katja Probst, Dennis Nurjadi, Klaus Heeg, Anne-Marie Frede, Alexander H. Dalpke and Sébastien Boutin

Antibiotics 2021, 10(6), 726; https://doi.org/10.3390/antibiotics10060726 - 16 Jun 2021

Cited by 6 | Viewed by 7356

Abstract

Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study [...] Read more.

Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study was to compare the performance of WGS and real-time multiplex PCR (RT-qPCR) for diagnosing carbapenem-resistant Enterobacterales. In this study, we analyzed 92 phenotypically carbapenem-resistant Enterobacterales, sent to the University Hospital Heidelberg in 2019, by the carbapenem inactivation method (CIM) and compared WGS and RT-qPCR as genotypic carbapenemase detection methods. In total, 80.4% of the collected isolates were identified as carbapenemase producers. For six isolates, discordant results were recorded for WGS, PCR and CIM, as the carbapenemase genes were initially not detected by WGS. A reanalysis using raw reads, rather than assembly, highlighted a coverage issue with failure to detect carbapenemases located in contigs with a coverage lower than 10×, which were then discarded. Our study shows that multiplex RT-qPCR and CIM can be a simple alternative to WGS for basic surveillance of carbapenemase-producing Enterobacterales. Using WGS in clinical workflow has some limitations, especially regarding coverage and sensitivity. We demonstrate that antimicrobial resistance gene detection should be performed on the raw reads or non-curated draft genome to increase sensitivity. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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11 pages, 469 KiB

Open AccessArticle

Carriage of Carbapenem-Resistant Enterobacterales in Adult Patients Admitted to a University Hospital in Italy

by Pamela Barbadoro, Daniela Bencardino, Elisa Carloni, Enrica Omiccioli, Elisa Ponzio, Rebecca Micheletti, Giorgia Acquaviva, Aurora Luciani, Annamaria Masucci, Antonella Pocognoli, Francesca Orecchioni, Marcello Mario D’Errico, Mauro Magnani and Francesca Andreoni

Antibiotics 2021, 10(1), 61; https://doi.org/10.3390/antibiotics10010061 - 10 Jan 2021

Cited by 12 | Viewed by 3102

Abstract

The emerging spread of carbapenemase-producing Enterobacterales (CPE) strains, in particular, Klebsiella pneumoniae and Escherichia coli, has become a significant threat to hospitalized patients. Carbapenemase genes are frequently located on plasmids than can be exchanged among clonal strains, increasing the antibiotic resistance rate. [...] Read more.

The emerging spread of carbapenemase-producing Enterobacterales (CPE) strains, in particular, Klebsiella pneumoniae and Escherichia coli, has become a significant threat to hospitalized patients. Carbapenemase genes are frequently located on plasmids than can be exchanged among clonal strains, increasing the antibiotic resistance rate. The aim of this study was to determine the prevalence of CPE in patients upon their admission and to analyze selected associated factors. An investigation of the antibiotic resistance and genetic features of circulating CPE was carried out. Phenotypic tests and molecular typing were performed on 48 carbapenemase-producing strains of K. pneumoniae and E. coli collected from rectal swabs of adult patients. Carbapenem-resistance was confirmed by PCR detection of resistance genes. All strains were analyzed by PCR-based replicon typing (PBRT) and multilocus sequence typing (MLST) was performed on a representative isolate of each PBRT profile. More than 50% of the strains were found to be multidrug-resistant, and the bla_KPC gene was detected in all the isolates with the exception of an E. coli strain. A multireplicon status was observed, and the most prevalent profile was FIIK, FIB KQ (33%). MLST analysis revealed the prevalence of sequence type 512 (ST512). This study highlights the importance of screening patients upon their admission to limit the spread of CRE in hospitals. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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16 pages, 1712 KiB

Open AccessArticle

Phenotypic and Genotypic Features of Klebsiella pneumoniae Harboring Carbapenemases in Egypt: OXA-48-Like Carbapenemases as an Investigated Model

by Suzan Mohammed Ragheb, Mahmoud Mohamed Tawfick, Amani Ali El-Kholy and Abeer Khairy Abdulall

Antibiotics 2020, 9(12), 852; https://doi.org/10.3390/antibiotics9120852 - 28 Nov 2020

Cited by 30 | Viewed by 3757

Abstract

This study aimed at the characterization of carbapenem-resistant Klebsiella pneumoniae isolates focusing on typing of the bla_OXA-48-like genes. Additionally, the correlation between the resistance pattern and biofilm formation capacity of the carbapenem-resistant K. pneumoniae isolates was studied. The collected isolates were assessed [...] Read more.

This study aimed at the characterization of carbapenem-resistant Klebsiella pneumoniae isolates focusing on typing of the bla_OXA-48-like genes. Additionally, the correlation between the resistance pattern and biofilm formation capacity of the carbapenem-resistant K. pneumoniae isolates was studied. The collected isolates were assessed for their antimicrobial resistance and carbapenemases production by a modified Hodge test and inhibitor-based tests. The carbapenemases encoding genes (bla_KPC, bla_NDM, bla_VIM, bla_IMP, and bla_OXA-48-like) were detected by PCR. Isolates harboring bla_OXA-48-like genes were genotyped by Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction (ERIC-PCR) and plasmid profile analysis. The discriminatory power of the three typing methods (antibiogram, ERIC-PCR, and plasmid profile analysis) was compared by calculation of Simpson’s Diversity Index (SDI). The transferability of bla_OXA-48 gene was tested by chemical transformation. The biofilm formation capacity and the prevalence of the genes encoding the fimbrial adhesins (fimH-1 and mrkD) were investigated. The isolates showed remarkable resistance to β-lactams and non-β-lactams antimicrobials. The coexistence of the investigated carbapenemases encoding genes was prevalent except for only 15 isolates. The plasmid profile analysis had the highest discriminatory power (SDI = 0.98) in comparison with ERIC-PCR (SDI = 0.89) and antibiogram (SDI = 0.78). The transferability of bla_OXA-48 gene was unsuccessful. All isolates were biofilm formers with the absence of a significant correlation between the biofilm formation capacity and resistance profile. The genes fimH-1 and mrkD were prevalent among the isolates. The prevalence of carbapenemases encoding genes, especially bla_OXA-48-like genes in Egyptian healthcare settings, is worrisome and necessitates further strict dissemination control measures. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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19 pages, 2524 KiB

Open AccessArticle

Extended Spectrum Beta-Lactamase-Resistant Determinants among Carbapenem-Resistant Enterobacteriaceae from Beef Cattle in the North West Province, South Africa: A Critical Assessment of Their Possible Public Health Implications

by Lungisile Tshitshi, Madira Coutlyne Manganyi, Peter Kotsoana Montso, Moses Mbewe and Collins Njie Ateba

Antibiotics 2020, 9(11), 820; https://doi.org/10.3390/antibiotics9110820 - 17 Nov 2020

Cited by 20 | Viewed by 3809

Abstract

Carbapenems are considered to be the last resort antibiotics for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing strains. The purpose of this study was to assess antimicrobial resistance profile of Carbapenem-resistant Enterobacteriaceae (CRE) isolated from cattle faeces and determine the presence [...] Read more.

Carbapenems are considered to be the last resort antibiotics for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing strains. The purpose of this study was to assess antimicrobial resistance profile of Carbapenem-resistant Enterobacteriaceae (CRE) isolated from cattle faeces and determine the presence of carbapenemase and ESBL encoding genes. A total of 233 faecal samples were collected from cattle and analysed for the presence of CRE. The CRE isolates revealed resistance phenotypes against imipenem (42%), ertapenem (35%), doripenem (30%), meropenem (28%), cefotaxime, (59.6%) aztreonam (54.3%) and cefuroxime (47.7%). Multidrug resistance phenotypes ranged from 1.4 to 27% while multi antibiotic resistance (MAR) index value ranged from 0.23 to 0.69, with an average of 0.40. Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabilis) and Salmonella (34.4, 43.7, 1.3 and 4.6%, respectively) were the most frequented detected species through genus specific PCR analysis. Detection of genes encoding carbapenemase ranged from 3.3% to 35% (blaKPC, blaNDM, blaGES, blaOXA-48, blaVIM and blaOXA-23). Furthermore, CRE isolates harboured ESBL genes (blaSHV (33.1%), blaTEM (22.5%), blaCTX-M (20.5%) and blaOXA (11.3%)). In conclusion, these findings indicate that cattle harbour CRE carrying ESBL determinants and thus, proper hygiene measures must be enforced to mitigate the spread of CRE strains to food products. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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11 pages, 269 KiB

Open AccessArticle

Multiplicity of Carbapenemase-Producers Three Years after a KPC-3-Producing K. pneumoniae ST147-K64 Hospital Outbreak

by Ana Margarida Guerra, Agostinho Lira, Angelina Lameirão, Aurélia Selaru, Gabriela Abreu, Paulo Lopes, Margarida Mota, Ângela Novais and Luísa Peixe

Antibiotics 2020, 9(11), 806; https://doi.org/10.3390/antibiotics9110806 - 13 Nov 2020

Cited by 20 | Viewed by 2088

Abstract

Carbapenem resistance rates increased exponentially between 2014 and 2017 in Portugal (~80%), especially in Klebsiella pneumoniae. We characterized the population of carbapanemase-producing Enterobacterales (CPE) infecting or colonizing hospitalized patients (2017–2018) in a central hospital from northern Portugal, where KPC-3-producing K. pneumoniae capsular [...] Read more.

Carbapenem resistance rates increased exponentially between 2014 and 2017 in Portugal (~80%), especially in Klebsiella pneumoniae. We characterized the population of carbapanemase-producing Enterobacterales (CPE) infecting or colonizing hospitalized patients (2017–2018) in a central hospital from northern Portugal, where KPC-3-producing K. pneumoniae capsular type K64 has caused an initial outbreak. We gathered phenotypic (susceptibility data), molecular (population structure, carbapenemase, capsular type) and biochemical (FT-IR) data, together with patients’ clinical and epidemiological information. A high diversity of Enterobacterales species, clones (including E. coli ST131) and carbapenemases (mainly KPC-3 but also OXA-48 and VIM) was identified three years after the onset of carbapenemases spread in the hospital studied. ST147-K64 K. pneumoniae, the initial outbreak clone, is still predominant though other high-risk clones have emerged (e.g., ST307, ST392, ST22), some of them with pandrug resistance profiles. Rectal carriage, previous hospitalization or antibiotherapy were presumptively identified as risk factors for subsequent infection. In addition, our previously described Fourier Transform infrared (FT-IR) spectroscopy method typed 94% of K. pneumoniae isolates with high accuracy (98%), and allowed to identify previously circulating clones. This work highlights an increasing diversity of CPE infecting or colonizing patients in Portugal, despite the infection control measures applied, and the need to improve the accuracy and speed of bacterial strain typing, a goal that can be met by simple and cost-effective FT-IR based typing. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

13 pages, 8617 KiB

Open AccessArticle

Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

by Kyriaki Xanthopoulou, Alessandra Carattoli, Julia Wille, Lena M. Biehl, Holger Rohde, Fedja Farowski, Oleg Krut, Laura Villa, Claudia Feudi, Harald Seifert and Paul G Higgins

Antibiotics 2020, 9(10), 675; https://doi.org/10.3390/antibiotics9100675 - 5 Oct 2020

Cited by 20 | Viewed by 4303

Abstract

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms [...] Read more.

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the bla_OXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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Review

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21 pages, 1534 KiB

Open AccessReview

Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment

by Gurleen Taggar, Muhammad Attiq Rehman, Patrick Boerlin and Moussa Sory Diarra

Antibiotics 2020, 9(10), 693; https://doi.org/10.3390/antibiotics9100693 - 13 Oct 2020

Cited by 60 | Viewed by 5879

Abstract

The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem [...] Read more.

The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (bla_KPC), class B (bla_IMP, bla_VIM, bla_NDM), and class D (bla_OXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment. Full article

(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)

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