scholarly journals Characterization of a Novel AmpC β-Lactamase Produced by a Carbapenem-Resistant Cedecea davisae Clinical Isolate

2014 ◽  
Vol 58 (11) ◽  
pp. 6942-6945 ◽  
Author(s):  
Nacim Ammenouche ◽  
Hervé Dupont ◽  
Hedi Mammeri
Keyword(s):  
Susceptibility Testing ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Third Generation ◽  
Enzymatic Characterization ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Third Generation Cephalosporins ◽  
Cloning Experiment

ABSTRACTACedecea davisaeisolate, which was intermediate or resistant to third-generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC β-lactamase expression combined with porin deficiency accounted for the carbapenem resistance. A cloning experiment followed by phenotypic and enzymatic characterization identified a novel class C enzyme that was phylogenetically and biochemically close to the chromosome-borne β-lactamases of the generaEnterobacterandCitrobacter.

scholarly journals OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

2011 ◽  
Vol 55 (10) ◽  
pp. 4742-4747 ◽  
Author(s):  
Laura García-Sureda ◽  
Antonio Doménech-Sánchez ◽  
Mariette Barbier ◽  
Carlos Juan ◽  
Joan Gascó ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Identical Result ◽  
Sequencing Analysis ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

scholarly journals Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin-Producing Strains of Escherichia coli O157:H7 in Japan

2015 ◽  
Vol 53 (9) ◽  
pp. 3035-3038 ◽  
Author(s):  
Ryuji Kawahara ◽  
Kazuko Seto ◽  
Masumi Taguchi ◽  
Chie Nakajima ◽  
Yuko Kumeda ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Shiga Toxin ◽  
Generation Cephalosporin ◽  
Escherichia Coli O157 ◽  
Third Generation ◽  
Content Type ◽  
Resistant Strains ◽  
Third Generation Cephalosporins

We isolated Shiga toxin-producingEscherichia coliO157:H7 strains resistant to third-generation cephalosporins. The resistant strains harboredblaCMY-2, a plasmid-mediated AmpC β-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboringblaCMY-2.

scholarly journals 4-Amino-2-Sulfanylbenzoic Acid as a Potent Subclass B3 Metallo-β-Lactamase-Specific Inhibitor Applicable for Distinguishing Metallo-β-Lactamase Subclasses

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Jun-ichi Wachino ◽  
Reo Kanechi ◽  
Erina Nishino ◽  
Marie Mochizuki ◽  
Wanchun Jin ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Conserved Residues ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Promising Strategy ◽  
Starting Point

ABSTRACT The number of cases of infection with carbapenem-resistant Enterobacteriaceae (CRE) has been increasing and has become a major clinical and public health concern. Production of metallo-β-lactamases (MBLs) is one of the principal carbapenem resistance mechanisms in CRE. Therefore, developing MBL inhibitors is a promising strategy to overcome the problems of carbapenem resistance conferred by MBLs. To date, the development and evaluation of MBL inhibitors have focused on subclass B1 MBLs but not on B3 MBLs. In the present study, we searched for B3 MBL (specifically, SMB-1) inhibitors and found thiosalicylic acid (TSA) to be a potent inhibitor of B3 SMB-1 MBL (50% inhibitory concentration [IC50], 0.95 μM). TSA inhibited the purified SMB-1 to a considerable degree but was not active against Escherichia coli cells producing SMB-1, as the meropenem (MEM) MIC for the SMB-1 producer was only slightly reduced with TSA. We then introduced a primary amine to TSA and synthesized 4-amino-2-sulfanylbenzoic acid (ASB), which substantially reduced the MEM MICs for SMB-1 producers. X-ray crystallographic analyses revealed that ASB binds to the two zinc ions, Ser221, and Thr223 at the active site of SMB-1. These are ubiquitously conserved residues across clinically relevant B3 MBLs. ASB also significantly inhibited other B3 MBLs, including AIM-1, LMB-1, and L1. Therefore, the characterization of ASB provides a starting point for the development of optimum B3 MBL inhibitors.

scholarly journals Genomic Epidemiology of Klebsiella pneumoniae in Italy and Novel Insights into the Origin and Global Evolution of Its Resistance to Carbapenem Antibiotics

2014 ◽  
Vol 59 (1) ◽  
pp. 389-396 ◽  
Author(s):  
Stefano Gaiarsa ◽  
Francesco Comandatore ◽  
Paolo Gaibani ◽  
Marta Corbella ◽  
Claudia Dalla Valle ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pathogenic Bacteria ◽  
High Morbidity ◽  
Third Generation ◽  
Data Set ◽  
Content Type ◽  
Genomic Epidemiology ◽  
Carbapenem Resistant ◽  
Resistant Group ◽  
Third Generation Cephalosporins

ABSTRACTKlebsiella pneumoniaeis at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated withK. pneumoniaeinfections in nosocomial environments. We sequenced the genomes of 89K. pneumoniaestrains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology ofK. pneumoniaein Italy. Thirty-one strains were carbapenem-resistantK. pneumoniaecarbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity ofK. pneumoniaeworldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ∼1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group ofK. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding ofK. pneumoniaeevolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy.

scholarly journals Characterization of an Enterobacter cloacae Strain Producing both KPC and NDM Carbapenemases by Whole-Genome Sequencing

2015 ◽  
Vol 59 (10) ◽  
pp. 6625-6628 ◽  
Author(s):  
Wenjing Wu ◽  
Yu Feng ◽  
Alessandra Carattoli ◽  
Zhiyong Zong
Keyword(s):  
Whole Genome Sequencing ◽  
Bloodstream Infection ◽  
Genome Sequencing ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Whole Genome ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTA carbapenem-resistantEnterobacter cloacaestrain, WCHECl-14653, causing a fatal bloodstream infection, was characterized by genome sequencing and conjugation experiments. The strain carried two carbapenemase genes,blaNDM-1andblaKPC-2, on separate IncF plasmids. The coexistence ofblaNDM-1andblaKPC-2conferred slightly higher-level carbapenem resistance compared with that ofblaNDM-1orblaKPC-2alone, and the coexistence of two IncF plasmids may generate new platforms for spreading carbapenemase genes.

scholarly journals Molecular Characterization of Klebsiella pneumoniae Clinical Isolates with Elevated Resistance to Carbapenems

2017 ◽  
Vol 11 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Rasha Barwa ◽  
Mona Shaaban
Keyword(s):  
Random Amplified Polymorphic Dna ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Copy Numbers ◽  
Broth Microdilution Method ◽  
High Level ◽  
Urine Specimens

Background: Emergence of carbapenems-resistant K. pneumoniae represents a serious challenge for antimicrobial therapy. Objective: The aim of this research is to determine different mechanisms mediating the emergence of K. pneumoniae isolates with high-level carbapenem resistance. Method: A total of 80 K. pneumoniae isolates were purified from sputum and urine specimens. The minimum inhibitory concentrations (MICs) of imipenem and meropenem were determined by broth microdilution method. Carbapenemases were detected by Modified Hodge test and PCR. Additionally, the copy numbers of the identified genes (blaVIM-1, blaNDM-1 and blaOXA-48) were quantified by RT-PCR. The outer membrane proteins OmpK35 and OmpK36 of the resistant isolates were analyzed. Results: Eight isolates were resistant to carbapenems; six of these isolates possessed elevated MICs to imipenem and meropenem (≥16 µg/ml). Carbapenem resistant isolates harbored blaNDM-1 (n=5), blaVIM-1 (n=4) and blaOXA-48 (n=1) with some isolates had multiple carbapenemases genes. Six isolates with high MICs to imipenem contained multi-copies of the carbapenemases genes along with the lack of OmpK35. Isolates with intermediate resistance to carbapenems (MIC; 4-8 µg/ml) did not exhibit multiple carbapenemases but lacked the OmpK35. Random amplified polymorphic DNA exhibited three different patterns and indicated that five isolates encoded the same pattern P1. Conclusion: This study elucidated that multiple carbapenemases genes, high copy number of carbapenemases and loss of the porin OmpK35 could collectively contribute to the emergence of K. pneumoniae isolates with high resistance to carbapenems. Hence, more restrictions should be applied on the use of carbapenems to reduce the emergence of the resistant clones.

scholarly journals Metronidazole- and Carbapenem-Resistant Bacteroides thetaiotaomicron Isolated in Rochester, Minnesota, in 2014

2015 ◽  
Vol 59 (7) ◽  
pp. 4157-4161 ◽  
Author(s):  
Sapna P. Sadarangani ◽  
Scott A. Cunningham ◽  
Patricio R. Jeraldo ◽  
John W. Wilson ◽  
Reeti Khare ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Susceptibility Testing ◽  
Clinical Medicine ◽  
Anaerobic Bacteria ◽  
Carbapenem Resistance ◽  
Whole Genome ◽  
Abdominal Abscess ◽  
Bacteroides Thetaiotaomicron ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTEmerging antimicrobial resistance in members of theBacteroides fragilisgroup is a concern in clinical medicine. Although metronidazole and carbapenem resistance have been reported inBacteroides thetaiotaomicron, a member of theB. fragilisgroup, they have not, to the best of our knowledge, been reported together in the sameB. thetaiotaomicronisolate. Herein, we report isolation of piperacillin-tazobactam-, metronidazole-, clindamycin-, ertapenem-, and meropenem-resistantB. thetaiotaomicronfrom a patient with postoperative intra-abdominal abscess and empyema. Whole-genome sequencing demonstrated the presence ofnimDwith at least a portion of IS1169upstream, a second putativenimgene, two β-lactamase genes (one of which has not been previously reported), twotetXgenes,tetQ,ermF, twocatgenes, and a number of efflux pumps. This report highlights emerging antimicrobial resistance inB. thetaiotaomicronand the importance of identification and antimicrobial susceptibility testing of selected anaerobic bacteria.

scholarly journals Effects of Klebsiella pneumoniae Carbapenemase Subtypes, Extended-Spectrum β-Lactamases, and Porin Mutations on theIn VitroActivity of Ceftazidime-Avibactam against Carbapenem-Resistant K. pneumoniae

2015 ◽  
Vol 59 (9) ◽  
pp. 5793-5797 ◽  
Author(s):  
Ryan K. Shields ◽  
Cornelius J. Clancy ◽  
Binghua Hao ◽  
Liang Chen ◽  
Ellen G. Press ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Emergence Of Resistance

ABSTRACTAvibactam is a novel β-lactamase inhibitor with affinity forKlebsiella pneumoniaecarbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producingK. pneumoniae(KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum β-lactamases (ESBLs). Mutations in porin geneompK36confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL andompK36mutations. Ceftazidime MICs ranged from 64 to 4,096 μg/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (≤4 μg/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 μg/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (P= 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (P= 0.003 andP= 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance.

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 Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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