scholarly journals Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Enterobacter cloacae Complex Isolated from Chinese Patients During 2004–2018

2021 ◽  
Vol Volume 14 ◽  
pp. 3647-3658
Author(s):  
Shixing Liu ◽  
Na Huang ◽  
Cui Zhou ◽  
Yishuai Lin ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Enterobacter Cloacae ◽  
Chinese Patients ◽  
Carbapenem Resistant ◽  
Enterobacter Cloacae Complex

scholarly journals Distinctive features of ertapenem mono-resistant carbapenem-resistant Enterobacterales in the United States: A cohort study

2021 ◽  
Author(s):  
Max W Adelman ◽  
Chris W Bower ◽  
Julian E Grass ◽  
Uzma A Ansari ◽  
Elizabeth A Soda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Enterobacter Cloacae ◽  
The United States ◽  
Resistant Bacteria ◽  
Emerging Infections ◽  
Logistic Regression Models ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Sterile Site ◽  
Enterobacter Cloacae Complex

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem “mono-resistant”) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed surveillance data from nine CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem “mono-resistant” cases to “other” CRE cases (resistant to ≥1 carbapenem other than ertapenem), and analyzed risk factors for mortality. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE. Ertapenem mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs. 19.5%, p<0.0001) and female (67.9% vs 59.0%, p<0.0001). Ertapenem mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs. 15.4%, p<0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p<0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p<0.0001). Ertapenem mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio 1.93, 95% confidence interval 1.30-2.86). Conclusions Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available.

scholarly journals Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
David A. Boyd ◽  
Laura F. Mataseje ◽  
Ross Davidson ◽  
Johannes A. Delport ◽  
Jeff Fuller ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Reference Laboratory ◽  
Chromosomal Locus ◽  
Complex Species ◽  
Content Type ◽  
Class A ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Enterobacter Ludwigii ◽  
Enterobacter Cloacae Complex

ABSTRACT Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (n = 10), IMI-1 (n = 5), and IMI-9 (n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla IMI-5 and bla IMI-6, were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI-type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential.

scholarly journals A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Hajime Kanamori ◽  
Christian M. Parobek ◽  
Jonathan J. Juliano ◽  
David van Duin ◽  
Bruce A. Cairns ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Molecular Mechanisms ◽  
Enterobacter Cloacae ◽  
The United States ◽  
Multidrug Resistant ◽  
Control Measures ◽  
Content Type ◽  
Burn Center ◽  
Infection Control Measures ◽  
Carbapenem Resistant

ABSTRACT Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE E. cloacae and K. pneumoniae over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including E. cloacae (n = 15) and K. pneumoniae (n = 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing E. cloacae and K. pneumoniae. This outbreak was primarily maintained by a clonal expansion of E. cloacae sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of bla KPC-3 was transmitted via an identical Tn4401b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPC-producing Enterobacteriaceae in their ability to utilize multiple modes to resistance gene propagation.

Molecular characterisation of carbapenem-resistant Enterobacter cloacae complex in Colombia: bla KPC and the ‘changing landscape’

2018 ◽  
Vol 13 ◽  
pp. 184-189 ◽  
Author(s):  
Elsa De La Cadena ◽  
Adriana Correa ◽  
Juan Sebastián Muñoz ◽  
Laura J. Rojas ◽  
Cristhian Hernández-Gómez ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Molecular Characterisation ◽  
Carbapenem Resistant ◽  
Enterobacter Cloacae Complex

scholarly journals Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Pegah Kananizadeh ◽  
Satoshi Oshiro ◽  
Shin Watanabe ◽  
Shu Iwata ◽  
Kyoko Kuwahara-Arai ◽  
...  
Keyword(s):  
Enterobacter Cloacae ◽  
Carbapenem Resistant ◽  
Enterobacter Cloacae Complex

scholarly journals 177. Distinctive Features of Ertapenem Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S108-S109
Author(s):  
Max W Adelman ◽  
Chris W Bower ◽  
Julian E Grass ◽  
Uzma Ansari ◽  
Isaac See ◽  
...  
Keyword(s):  
Risk Factors ◽  
Polymerase Chain Reaction ◽  
Survival Analysis ◽  
Enterobacter Cloacae ◽  
Incident Case ◽  
Chain Reaction ◽  
Carbapenem Resistant ◽  
Sterile Site ◽  
Polymerase Chain ◽  
Enterobacter Cloacae Complex

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem mono-resistant) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed laboratory- and population-based surveillance data from nine sites participating in CDC’s Emerging Infections Program (EIP). We defined an incident case as the first isolation of Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem (determined at clinical laboratory) from a normally sterile site or urine identified from a resident of the EIP catchment area in 2016-2017. We compared risk factors, carbapenemase genes (determined via polymerase chain reaction at CDC), and mortality of cases with ertapenem “mono-resistant” to “other” CRE (resistant to ≥ 1 carbapenem other than ertapenem). We additionally conducted survival analysis to determine the effect of ertapenem mono-resistant status and isolate source (sterile vs. urine) on survival. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE (Figure 1). Ertapenem mono-resistant CRE cases were more frequently ≥ 80 years old (29.1% vs. 19.5%, p< 0.0001), female (67.9% vs 59.0%, p< 0.0001), and white (62.6% vs. 45.1%, p< 0.0001). Ertapenem mono-resistant isolates were more likely than other CRE to be Enterobacter cloacae complex (48.4% vs. 15.4%, p< 0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p< 0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p< 0.0001) (Figure 2). Ertapenem mono-resistance was not associated with difference in 90-day mortality (unadjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.63-1.06) in logistic models or survival analysis (Figure 3). Figure 1. Flow diagram of carbapenem-resistant Enterobacterales cases included in analysis, 2017-2018. CRE, carbapenem-resistant Enterobacterales; MIC, minimum inhibitory concentration. Ertapenem mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. We excluded isolates that (1) had no interpretable MICs for any carbapenem, (2) were only tested against ertapenem, (3) had unknown death status, or (4) were not associated with patient’s first incident case. Figure 2. Proportion of ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) vs. other CRE isolates with specific carbapenemase genes. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-ß-lactamase; OXA, oxacillinase. Ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Testing via reverse transcriptase polymerase chain reaction. Figure 3. Survival analysis comparing patients with carbapenem-resistant Enterobacterales (CRE) that are ertapenem mono-resistant to other CRE (i.e., resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (B). Ertapenem mono-resistant) isolates were not associated with decreased mortality, and sterile isolate source (i.e., non-urinary isolates) was associated with increased mortality regardless of ertapenem mono-resistance. Conclusion Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. These findings may inform antibiotic choice particularly when testing for carbapenemases is not readily available. Disclosures All Authors: No reported disclosures

Expression of AraC/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes

2020 ◽  
Vol 75 (5) ◽  
pp. 1146-1150
Author(s):  
Piotr Majewski ◽  
Anna Gutowska ◽  
Pawel Sacha ◽  
Thamarai Schneiders ◽  
Mariola Talalaj ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Molecular Mechanisms ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Modern Medicine ◽  
Regulatory Genes ◽  
Global Regulator ◽  
Response Regulators ◽  
Bacterial Membranes ◽  
Carbapenem Resistant

Abstract Background The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine. Objectives We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period. Methods The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility. Results In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation. Conclusions Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.

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