scholarly journals Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Brian D. Johnston ◽  
Paul Thuras ◽  
Stephen B. Porter ◽  
Melissa Anacker ◽  
Brittany VonBank ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
The United States ◽  
Asia Pacific ◽  
Beta Lactamase ◽  
Content Type ◽  
Beta Lactamases ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Primary Agent

ABSTRACT Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

scholarly journals Activity of Imipenem-Relebactam against Carbapenem-Resistant Escherichia coli Isolates from the United States in Relation to Clonal Background, Resistance Genes, Coresistance, and Region

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Brian D. Johnston ◽  
Paul Thuras ◽  
Stephen B. Porter ◽  
Melissa Anacker ◽  
Brittany VonBank ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Beta Lactamase ◽  
Content Type ◽  
E Coli ◽  
Highly Active ◽  
Carbapenem Resistant

ABSTRACT Imipenem-relebactam (I-R) is a recently developed carbapenem–beta-lactamase inhibitor combination agent that can overcome carbapenem resistance, which has now emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. To clarify the likely utility of I-R for carbapenem-resistant (CR) E. coli infections in the United States, we characterized 203 recent CR clinical E. coli isolates from across the United States (years 2002 to 2017) for phylogroup, clonal group (including ST131, H30R, and the CTX-M-15-associated H30Rx subset within H30R), relevant beta-lactamase genes, and broth microdilution MICs for I-R and 11 comparator agents. Overall, I-R was highly active (89% susceptible), more so than all comparators except tigecycline and colistin (both 99% susceptible). I-R’s activity varied significantly in relation to phylogroup, clonal background, resistance genotype, and region. It was greatest among phylogroup B2, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive, and northeast U.S. isolates and lowest among phylogroup C, New Delhi metallo-β-lactamase (NDM)-positive, and southeast U.S. isolates. Relebactam improved imipenem’s activity against CR isolates within each phylogroup—especially groups A, B1, and B2—and particularly against isolates containing KPC. I-R remained substantially active against isolates coresistant to comparator agents, albeit somewhat less so than against the corresponding susceptible isolates. These findings suggest that I-R should be useful for treating most CR E. coli infections in the United States, largely independent of coresistance, although this likely will vary in relation to the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

scholarly journals Complete Genome Sequence of a Carbapenem-Resistant Escherichia coli Isolate with blaNDM-5 from a Dog in the United States

2019 ◽  
Vol 8 (34) ◽  
Author(s):  
Gregory H. Tyson ◽  
Cong Li ◽  
Olgica Ceric ◽  
Renate Reimschuessel ◽  
Stephen Cole ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Carbapenem Resistance ◽  
The United States ◽  
Multidrug Resistant ◽  
Content Type ◽  
E Coli

The carbapenem resistance gene bla NDM-5 was identified in an Escherichia coli strain isolated from a dog. We report here the complete genome sequence of this E. coli strain; the bla NDM-5 gene was present on a large IncFII multidrug-resistant plasmid. This is the first bla NDM-5-carrying E. coli strain from an animal in the United States.

scholarly journals Molecular Diversity and Plasmid Analysis of KPC-Producing Escherichia coli

2016 ◽  
Vol 60 (7) ◽  
pp. 4073-4081 ◽  
Author(s):  
Kalyan D. Chavda ◽  
Liang Chen ◽  
Michael R. Jacobs ◽  
Robert A. Bonomo ◽  
Barry N. Kreiswirth
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Rapid Evolution ◽  
The United States ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Plasmid Analysis ◽  
Replication Gene ◽  
Sequence Types

ABSTRACTThe emergence and spread ofKlebsiella pneumoniaecarbapenemase (KPC) amongEnterobacteriaceaepresents a major public health threat to the world. Although not as common as inK. pneumoniae, KPC is also found inEscherichia colistrains. Here, we genetically characterized 9 carbapenem-resistantE. colistrains isolated from six hospitals in the United States and completely sequenced theirblaKPC-harboring plasmids. The nine strains were isolated from different geographical locations and belonged to 8 differentE. colisequence types. SevenblaKPC-harboring plasmids belonged to four different known incompatibility groups (IncN, -FIA, -FIIK2, and -FIIK1) and ranged in size from ∼16 kb to ∼241 kb. In this analysis, we also identified two plasmids that have novel replicons: (i) pBK28610, which is similar to p34978-3 with an insertion of Tn4401b, and (ii) pBK31611, which does not have an apparent homologue in the GenBank database. Moreover, we report the emergence of a pKP048-like plasmid, pBK34397, inE. coliin the United States. Meanwhile, we also found examples of interspecies spread ofblaKPCplasmids, as pBK34592 is identical to pBK30683, isolated fromK. pneumoniae. In addition, we discovered examples of acquisition (pBK32602 acquired an ∼46-kb fragment including a novel replication gene, along with Tn4401band other resistance genes) and/or loss (pKpQIL-Ec has a 14.5-kb deletion compared to pKpQIL-10 and pBK33689) of DNA, demonstrating the plasticity of these plasmids and their rapid evolution in the clinic. Overall, our study shows that the spread ofblaKPC-producingE. coliis largely due to horizontal transfer ofblaKPC-harboring plasmids and related mobile elements into diverse genetic backgrounds.

scholarly journals 646. Adapting the modified Carbapenem Inactivation Method to assess for possible beta-lactamase mediated resistance in Piperacillin-Tazobactam resistant/ Ceftriaxone susceptible Escherichia. coli and Klebsiella pneumoniae

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S382-S382
Author(s):  
Alexander Lawandi ◽  
Samuel De L’Etoile-Morel ◽  
Gleice C Leite ◽  
Todd C Lee
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
Generation Cephalosporin ◽  
Third Generation ◽  
Beta Lactamase ◽  
Review Of The Literature ◽  
Beta Lactamases ◽  
Resistance Phenotype ◽  
E Coli ◽  
Reference Strains

Abstract Background A cluster of piperacillin-tazobactam resistant/ceftriaxone susceptible Escherichia coli and Klebsiella pneumonaie bacteremias were noted at our institution. A review of the literature suggested this resistance phenotype was mediated by a beta-lactamase. We sought to further corroborate this phenotypically. Methods We adapted the “carbapenem inactivation method” utilizing piperacillin-tazobactam and ceftriaxone discs on all E. coli and K. pneumoniae isolated from blood and demonstrating piperacillin-tazobactam resistance but with ceftriaxone susceptibility. We utilized pan-susceptible and carbapenem resistance Enterobacteriaceae reference strains as well as third generation cephalosporin resistant, piperacillin-tazobactam susceptible isolates as controls. Results 96% of the piperacillin-tazobactam resistant, ceftriaxone susceptible strains demonstrated the capacity to degrade the piperacillin-tazobactam discs while 100% spared the ceftriaxone discs. 75% of the piperacillin-tazobactam susceptible, ceftriaxone resistant control strains spared the piperacillin-tazobactam discs while degrading the ceftriaxone discs. Conclusion The resistance phenotype observed is due to beta-lactamase production and the modified carbapenem inactivation method can be adapted to probe for other beta-lactamases. Further study is required to definitively identify which beta-lactamase is responsible. Disclosures All Authors: No reported disclosures

scholarly journals Plasmid-Mediated Imipenem-Hydrolyzing Enzyme KPC-2 among Multiple Carbapenem-Resistant Escherichia coli Clones in Israel

2006 ◽  
Vol 50 (9) ◽  
pp. 3098-3101 ◽  
Author(s):  
Shiri Navon-Venezia ◽  
Inna Chmelnitsky ◽  
Azita Leavitt ◽  
Mitchell J. Schwaber ◽  
David Schwartz ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Blot Analysis ◽  
Southern Blot Analysis ◽  
Medical Center ◽  
Carbapenem Resistance ◽  
The United States ◽  
E Coli ◽  
Tel Aviv ◽  
Carbapenem Resistant

ABSTRACT Carbapenem resistance in Escherichia coli is rare. We report four genetically unrelated carbapenem-resistant E. coli isolates cultured from four patients hospitalized in Tel Aviv Medical Center. PCR, sequencing, and Southern blot analysis identified KPC-2 as the imipenem-hydrolyzing enzyme in all four strains, carried on different plasmids with a possible common origin. This is the first discovery of KPC-2 in E. coli and the first report of this enzyme originating outside the United States.

scholarly journals Acquisition of Carbapenem Resistance by Plasmid-Encoded-AmpC-Expressing Escherichia coli

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Ria van Boxtel ◽  
Agnes A. Wattel ◽  
Jesús Arenas ◽  
Wil H. F. Goessens ◽  
Jan Tommassen
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
Plasmid Copy Number ◽  
Second Step ◽  
Plasmid Copy ◽  
Simultaneous Reduction ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Genetic Mechanisms

ABSTRACT Although AmpC β-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx into the periplasm by mutations in the porin genes. Here we investigated the route and genetic mechanisms of acquisition of carbapenem resistance in a clinical E. coli isolate carrying bla CMY-2 on a plasmid by selecting for mutants that are resistant to increasing concentrations of meropenem. In the first step, the expression of OmpC, the only porin produced in the strain under laboratory conditions, was lost, leading to reduced susceptibility to meropenem. In the second step, the expression of the CMY-2 β-lactamase was upregulated, leading to resistance to meropenem. The loss of OmpC was due to the insertion of an IS1 element into the ompC gene or to frameshift mutations and premature stop codons in this gene. The bla CMY-2 gene was found to be located on an IncIγ plasmid, and overproduction of the CMY-2 enzyme resulted from an increased plasmid copy number due to a nucleotide substitution in the inc gene. The clinical relevance of these genetic mechanisms became evident from the analysis of previously isolated carbapenem-resistant clinical isolates, which appeared to carry similar mutations.

scholarly journals Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Satlin ◽  
Liang Chen ◽  
Gopi Patel ◽  
Angela Gomez-Simmonds ◽  
Gregory Weston ◽  
...  
Keyword(s):  
New York ◽  
Empirical Therapy ◽  
Carbapenem Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Rapid Diagnostics ◽  
Multicenter Studies ◽  
Content Type ◽  
Medical Centers ◽  
Carbapenem Resistant

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

scholarly journals Investigation of Metallo-Beta-Lactamases in Carbapenem Resistant Pseudomonas aeruginosa Strains by Phenotypic and Genotypic Methods

2020 ◽  
Vol 25 (3) ◽  
pp. 301-307
Author(s):  
M. Duygu Aksoy ◽  
H. Murat Tuğrul
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ethylenediaminetetraacetic Acid ◽  
Carbapenem Resistance ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Synergy Test ◽  
Phenotypic Tests ◽  
Positive Controls

Introduction: Carbapenem resistant Pseudomonas aeruginosa strains cause serious problems in treatment. A large number of identified metallo-beta-lactamase (MBL) enzymes produced by P. aeruginosa are one of the most important mechanisms in resistance to carbapenems. MBL genes are located on the chromosome or plasmid, and they can easily spread between different bacterial strains. The activities of these enzymes are zinc-dependent, and they are inhibited by ethylenediaminetetraacetic acid (EDTA). Therefore, this advantage is used in MBL identification tests. In this study, it was aimed to determine MBL among P. aeruginosa strains. Materials and Methods: MBL existence was investigated in 35 P. aeruginosa strains accepted to be mildly susceptible/resistant to any of the carbapenem group of antibiotics through phenotypic and genotypic methods. Phenotypic tests were performed as double disk synergy test (DDST), combined disk diffusion tests (CDDT) by using 0.1 M and 0.5 M EDTA, MBL E-test, and modified Hodge test (MHT). blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaNDM gene were investigated by multiplex polimerase chain reaction (PCR) and PCR, respectively. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 standard bacteria were used in tests. VIM-1, VIM-2, IMP-13, SPM-1, NDM-1 type MBL-producing P. aeruginosa strains were used as positive controls. Results: Among the carbapenems resistant P. aeruginosa isolates, positivity of MBL was found as 54.2% by MBL E-test, 42.8% by DDST, 94.2% and 37.1% by CDDT method using 0.5 M and 0.1 M EDTA, respectively. Modified Hodge test and genotypic method did not detect MBL. Conclusion: In order to correctly evaluate the results of the phenotypic method, the investigation of resistance genes by molecular methods is also required. The most common metallo-beta-lactamase enzymes responsible for resistance to carbapenem in Pseudomonas were not observed. It was thought that different mechanisms might be responsible for the identified carbapenem resistance.

Statewide surveillance of carbapenemase-producing carbapenem-resistant Escherichia coli and Klebsiella species in Washington state, October 2012–December 2017

2020 ◽  
Vol 41 (6) ◽  
pp. 716-722
Author(s):  
Mimi R. Precit ◽  
Kelly Kauber ◽  
William A. Glover ◽  
Scott J. Weissman ◽  
Tashina Robinson ◽  
...  
Keyword(s):  
Public Health ◽  
Escherichia Coli ◽  
Health Care ◽  
The United States ◽  
Case Definition ◽  
Washington State ◽  
Public Health Department ◽  
Klebsiella Species ◽  
E Coli ◽  
Carbapenem Resistant

AbstractBackground:Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.Objective:To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.Design:Multicenter prospective surveillance study.Methods:Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.Results:From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.Conclusions:We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.

scholarly journals Extraintestinal Pathogenic and Antimicrobial-Resistant Escherichia coli, Including Sequence Type 131 (ST131), from Retail Chicken Breasts in the United States in 2013

2017 ◽  
Vol 83 (6) ◽  
Author(s):  
James R. Johnson ◽  
Stephen B. Porter ◽  
Brian Johnston ◽  
Paul Thuras ◽  
Sarah Clock ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Virulence Genes ◽  
Meat Products ◽  
The United States ◽  
Sequence Type ◽  
The Other ◽  
Antibiotic Resistant ◽  
Content Type ◽  
E Coli

ABSTRACT Chicken meat products are hypothesized to be vehicles for transmitting antimicrobial-resistant and extraintestinal pathogenic Escherichia coli (ExPEC) to consumers. To reassess this hypothesis in the current era of heightened concerns about antimicrobial use in food animals, we analyzed 175 chicken-source E. coli isolates from a 2013 Consumer Reports national survey. Isolates were screened by PCR for ExPEC-defining virulence genes. The 25 ExPEC isolates (12% of 175) and a 2:1 randomly selected set of 50 non-ExPEC isolates were assessed for their phylogenetic/clonal backgrounds and virulence genotypes for comparison with their resistance profiles and the claims on the retail packaging label (“organic,” “no antibiotics,” and “natural”). Compared with the findings for non-ExPEC isolates, the group of ExPEC isolates had a higher prevalence of phylogroup B2 isolates (44% versus 4%; P < 0.001) and a lower prevalence of phylogroup A isolates (4% versus 30%; P = 0.001), a higher prevalence of multiple individual virulence genes, higher virulence scores (median, 11 [range, 4 to 16] versus 8 [range, 1 to 14]; P = 0.001), and higher resistance scores (median, 4 [range, 0 to 8] versus 3 [range, 0 to 10]; P < 0.001). All five isolates of sequence type 131 (ST131) were ExPEC (P = 0.003), were as extensively resistant as the other isolates tested, and had higher virulence scores than the other isolates tested (median, 12 [range, 11 to 13] versus 8 [range, 1 to 16]; P = 0.005). Organic labeling predicted lower resistance scores (median, 2 [range, 0 to 3] versus 4 [range, 0 to 10]; P = 0.008) but no difference in ExPEC status or virulence scores. These findings document a persisting reservoir of extensively antimicrobial-resistant ExPEC isolates, including isolates from ST131, in retail chicken products in the United States, suggesting a potential public health threat. IMPORTANCE We found that among Escherichia coli isolates from retail chicken meat products purchased across the United States in 2013 (many of these isolates being extensively antibiotic resistant), a minority had genetic profiles suggesting an ability to cause extraintestinal infections in humans, such as urinary tract infection, implying a risk of foodborne disease. Although isolates from products labeled “organic” were less extensively antibiotic resistant than other isolates, they did not appear to be less virulent. These findings suggest that retail chicken products in the United States, even if they are labeled “organic,” pose a potential health threat to consumers because they are contaminated with extensively antibiotic-resistant and, presumably, virulent E. coli isolates.

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