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 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 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 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 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 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.

scholarly journals Genetic Determinants of Resistance to Extended-Spectrum Cephalosporin and Fluoroquinolone in Escherichia coli Isolated from Diseased Pigs in the United States

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Shivdeep Singh Hayer ◽  
Seunghyun Lim ◽  
Samuel Hong ◽  
Ehud Elnekave ◽  
Timothy Johnson ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
High Risk ◽  
The United States ◽  
Genetic Determinants ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum ◽  
Animal Populations ◽  
Swine Population

ABSTRACT Fluoroquinolones and cephalosporins are critically important antimicrobial classes for both human and veterinary medicine. We previously found a drastic increase in enrofloxacin resistance in clinical Escherichia coli isolates collected from diseased pigs from the United States over 10 years (2006 to 2016). However, the genetic determinants responsible for this increase have yet to be determined. The aim of the present study was to identify and characterize the genetic basis of resistance against fluoroquinolones (enrofloxacin) and extended-spectrum cephalosporins (ceftiofur) in swine E. coli isolates using whole-genome sequencing (WGS). blaCMY-2 (carried by IncA/C2, IncI1, and IncI2 plasmids), blaCTX-M (carried by IncF, IncHI2, and IncN plasmids), and blaSHV-12 (carried by IncHI2 plasmids) genes were present in 87 (82.1%), 19 (17.9%), and 3 (2.83%) of the 106 ceftiofur-resistant isolates, respectively. Of the 110 enrofloxacin-resistant isolates, 90 (81.8%) had chromosomal mutations in gyrA, gyrB, parA, and parC genes. Plasmid-mediated quinolone resistance genes [qnrB77, qnrB2, qnrS1, qnrS2, and aac-(6)-lb′-cr] borne on ColE, IncQ2, IncN, IncF, and IncHI2 plasmids were present in 24 (21.8%) of the enrofloxacin-resistant isolates. Virulent IncF plasmids present in swine E. coli isolates were highly similar to epidemic plasmids identified globally. High-risk E. coli clones, such as ST744, ST457, ST131, ST69, ST10, ST73, ST410, ST12, ST127, ST167, ST58, ST88, ST617, ST23, etc., were also found in the U.S. swine population. Additionally, the colistin resistance gene (mcr-9) was present in several isolates. This study adds valuable information regarding resistance to critical antimicrobials with implications for both animal and human health. IMPORTANCE Understanding the genetic mechanisms conferring resistance is critical to design informed control and preventive measures, particularly when involving critically important antimicrobial classes such as extended-spectrum cephalosporins and fluoroquinolones. The genetic determinants of extended-spectrum cephalosporin and fluoroquinolone resistance were highly diverse, with multiple plasmids, insertion sequences, and genes playing key roles in mediating resistance in swine Escherichia coli. Plasmids assembled in this study are known to be disseminated globally in both human and animal populations and environmental samples, and E. coli in pigs might be part of a global reservoir of key antimicrobial resistance (AMR) elements. Virulent plasmids found in this study have been shown to confer fitness advantages to pathogenic E. coli strains. The presence of international, high-risk zoonotic clones provides worrisome evidence that resistance in swine isolates may have indirect public health implications, and the swine population as a reservoir for these high-risk clones should be continuously monitored.

scholarly journals Molecular Characterization of Resistance to Extended-Spectrum Cephalosporins in Clinical Escherichia coli Isolates from Companion Animals in the United States

2011 ◽  
Vol 55 (12) ◽  
pp. 5666-5675 ◽  
Author(s):  
Bashar W. Shaheen ◽  
Rajesh Nayak ◽  
Steven L. Foley ◽  
Ohgew Kweon ◽  
Joanna Deck ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Regulatory Region ◽  
Companion Animals ◽  
The United States ◽  
Conjugative Plasmid ◽  
Chromosomal Gene ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum

ABSTRACTResistance to extended-spectrum cephalosporins (ESC) among members of the familyEnterobacteriaceaeoccurs worldwide; however, little is known about ESC resistance inEscherichia colistrains from companion animals. Clinical isolates ofE. coliwere collected from veterinary diagnostic laboratories throughout the United States from 2008 to 2009.E. coliisolates (n= 54) with reduced susceptibility to ceftazidime or cefotaxime (MIC ≥ 16 μg/ml) and extended-spectrum-β-lactamase (ESBL) phenotypes were analyzed. PCR and sequencing were used to detect mutations in ESBL-encoding genes and the regulatory region of the chromosomal geneampC. Conjugation experiments and plasmid identification were conducted to examine the transferability of resistance to ESCs. All isolates carried theblaCTX-M-1-group β-lactamase genes in addition to one or more of the following β-lactamase genes:blaTEM,blaSHV-3,blaCMY-2,blaCTX-M-14-like, andblaOXA-1.DifferentblaTEMsequence variants were detected in some isolates (n= 40). Three isolates harbored ablaTEM-181gene with a novel mutation resulting in an Ala184Val substitution. Approximately 78% of the isolates had mutations in promoter/attenuator regions of the chromosomal geneampC, one of which was a novel insertion of adenine between bases −28 and −29. Plasmids ranging in size from 11 to 233 kbp were detected in the isolates, with a common plasmid size of 93 kbp identified in 60% of isolates. Plasmid-mediated transfer of β-lactamase genes increased the MICs (≥16-fold) of ESCs for transconjugants. Replicon typing among isolates revealed the predominance of IncI and IncFIA plasmids, followed by IncFIB plasmids. This study shows the emergence of conjugative plasmid-borne ESBLs amongE. colistrains from companion animals in the United States, which may compromise the effective therapeutic use of ESCs in veterinary medicine.

scholarly journals Analysis of Serial Isolates of mcr-1-Positive Escherichia coli Reveals a Highly Active ISApl1 Transposon

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Erik Snesrud ◽  
Ana C. Ong ◽  
Brendan Corey ◽  
Yoon I. Kwak ◽  
Robert Clifford ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Stress Responses ◽  
Single Copy ◽  
The United States ◽  
Content Type ◽  
E Coli ◽  
Highly Active ◽  
Copy Numbers ◽  
Genes Encoding

ABSTRACT The emergence of a transferable colistin resistance gene (mcr-1) is of global concern. The insertion sequence ISApl1 is a key component in the mobilization of this gene, but its role remains poorly understood. Six Escherichia coli isolates were cultured from the same patient over the course of 1 month in Germany and the United States after a brief hospitalization in Bahrain for an unconnected illness. Four carried mcr-1 as determined by real-time PCR, but two were negative. Two additional mcr-1-negative E. coli isolates were collected during follow-up surveillance 9 months later. All isolates were analyzed by whole-genome sequencing (WGS). WGS revealed that the six initial isolates were composed of two distinct strains: an initial ST-617 E. coli strain harboring mcr-1 and a second, unrelated, mcr-1-negative ST-32 E. coli strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the mcr-1-negative ST-32 strain was still present. mcr-1 was associated with a single copy of ISApl1, located on a 64.5-kb IncI2 plasmid that shared >95% homology with other mcr-1 IncI2 plasmids. ISApl1 copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but ISApl1 movement was independent of mcr-1. Some movement was accompanied by gene disruption, including the loss of genes encoding proteins involved in stress responses, arginine catabolism, and l-arabinose utilization. These data represent the first comprehensive analysis of ISApl1 movement in serial clinical isolates and reveal that, under certain conditions, ISApl1 is a highly active IS element whose movement may be detrimental to the host cell.

scholarly journals Genetic Characterization of Escherichia coli O104 Isolates from Different Sources in the United States

2011 ◽  
Vol 78 (5) ◽  
pp. 1615-1618 ◽  
Author(s):  
Lydia V. Rump ◽  
Sonya Bodeis-Jones ◽  
Jason Abbott ◽  
Shaohua Zhao ◽  
Julie Kase ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Virulence Genes ◽  
Genetic Characterization ◽  
The United States ◽  
Content Type ◽  
E Coli ◽  
Virulence Markers ◽  
Different Sources

ABSTRACTEscherichia coliO104 isolates collected from different sources in the United States were examined for virulence genes typical of enterohemorrhagicE. coliand those identified in the O104:H4 isolate associated with the 2011 German outbreak. The unexpected presence of virulence markers in these isolates highlights the importance of screening unusual and potentially pathogenic Shiga toxin-producingE. coliserotypes.

Sign in / Sign up

Export Citation Format

Share Document