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 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 Determination of the frequency of carbapenemase producing Klebsiella pneumoniae isolates in Dhaka city, Bangladesh

2013 ◽  
Vol 2 (1) ◽  
pp. 28-30 ◽  
Author(s):  
Nawshad Hayder ◽  
Zahidul Hasan ◽  
Sadia Afrin ◽  
Rashed Noor
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Respiratory Diseases ◽  
High Morbidity ◽  
Wound Infections ◽  
Dhaka City ◽  
Carbapenem Resistant ◽  
Global Health Problem

Resistance of Klebsiella pneumoniae against carbapenem, imparted by the presence of carbapenemase, is an emerging global health problem with high morbidity and mortality. Thus, the present study attempted to detect the frequency of carbapenemase producing K. pneumoniae in Dhaka city of Bangladesh and thereby determine the health risk associated with their presence. A total of 647 K. pneumoniae isolates were detected from 2800 patients with urinary tract infection, bacterimia, wound infections and respiratory diseases. Thirty one carbapenem resistant isolates were found to harbor K. pneumoniae carbapenemase (KPC) through modified Hodge test. The KPC positive isolates were then subjected to the study of antibiogram and showed resistance against all the ß-lactam antibiotics along with carbapenems, while they were sensitive against colistin. Additionally, 287 isolates were found to be extended-spectrum ?-lactamases (ESBLs) positive apart from the KPC positive ones. DOI: http://dx.doi.org/10.3329/sjm.v2i1.15210 Stamford Journal of Microbiology, Vol.2(1) 2012: 28-30

scholarly journals Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Plasmid Dna ◽  
Clonal Expansion ◽  
Genetic Alterations ◽  
Sequence Type ◽  
Chromosomal Integration ◽  
Colistin Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

scholarly journals Epidemiology and Outcomes of Nontyphoidal Salmonella Bacteremias from England, 2004 to 2015

2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Shannon Katiyo ◽  
Berit Muller-Pebody ◽  
Mehdi Minaji ◽  
David Powell ◽  
Alan P. Johnson ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
High Morbidity ◽  
First Line ◽  
Data Set ◽  
Content Type ◽  
Increased Risk ◽  
Resistance Patterns ◽  
Prolonged Hospital ◽  
Antibiotic Resistance Patterns ◽  
Emergence Of Resistance

ABSTRACT Nontyphoidal Salmonella (NTS) bacteremia causes hospitalization and high morbidity and mortality. We linked Gastrointestinal Bacteria Reference Unit (GBRU) data to the Hospital Episode Statistics (HES) data set to study the trends and outcomes of NTS bacteremias in England between 2004 and 2015. All confirmed NTS isolates from blood from England submitted to GBRU between 1 January 2004 and 31 December 2015 were deterministically linked to HES records. Adjusted odds ratios (AOR), proportions, and confidence intervals (CI) were calculated to describe differences in age, sex, antibiotic resistance patterns, and serotypes over time. Males, neonates, and adults above 65 years were more likely to have NTS bacteremia (AOR, 1.54 [95% CI, 1.46 to 1.67]; 2.57 [95% CI, 1.43 to 4.60]; and 3.56 [95% CI, 3.25 to 3.90], respectively). Proportions of bacteremia increased from 1.41% in 2004 to 2.67% in 2015. Thirty-four percent of all blood isolates were resistant to a first-line antibiotic, and 1,397 (56%) blood isolates were linked to an HES record. Of the patients with NTS bacteremia, 969 (69%) had a cardiovascular condition and 155 (12%) patients died, out of which 120 (77%) patients were age 65 years and above. NTS bacteremia mainly affects older people with comorbidities placing them at increased risk of prolonged hospital stay and death. Resistance of invasive NTS to first-line antimicrobial agents appeared to be stable in England, but the emergence of resistance to last-resort antibiotics, such as colistin, requires careful monitoring.

scholarly journals Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Victor I. Band ◽  
Sarah W. Satola ◽  
Richard D. Smith ◽  
David A. Hufnagel ◽  
Chris Bower ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Diagnostic Testing ◽  
Cladistic Analysis ◽  
The United States ◽  
Clinical Diagnostics ◽  
Infection Model ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Clinical Diagnostic

ABSTRACT Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

scholarly journals Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains

2020 ◽  
Vol 6 (12) ◽  
Author(s):  
Katlego Kopotsa ◽  
Nontombi M. Mbelle ◽  
John Osei Sekyere
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Type I ◽  
Bacteriophage Therapy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Plasmid Replicon ◽  
Size Number ◽  
Plasmid Size ◽  
Epidemiological Trends

Carbapenem-resistant Klebsiella pneumoniae (CRKP) remains a major clinical pathogen and public health threat with few therapeutic options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping by repetitive element palindromic (REP)-PCR, plasmid size, number, incompatibility and mobility analyses, and PacBio’s SMRT sequencing (n=6). There were 56 multidrug-resistant CRKP, having bla OXA-48-like and bla NDM-1/7 carbapenemases on self-transmissible IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon was present in 56 strains. Whole-genome sequencing of six strains revealed least 41 virulence genes, extensive ompK36 mutations, and four different K- and O-loci types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring m6A (G A TC, G A TGNNNNNNTTG, CA A NNNNNNCATC motifs) and m4C (C C WGG) modifications on chromosomes and plasmids, were found. The nature of plasmid-mediated, clonal and multi-clonal dissemination of blaOXA-48-like and blaNDM-1 mirrors epidemiological trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both bla OXA-48 and bla NDM-1 in the same isolates was observed. Plasmid-mediated transmission of RMS, virulome and prophages influence bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on antimicrobial and bacteriophage therapy needs urgent investigation.

scholarly journals Sequence Type 273 Carbapenem-Resistant Klebsiella pneumoniae Carrying bla NDM-1 and bla IMP-4

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Lu Liu ◽  
Yu Feng ◽  
Haiyan Long ◽  
Alan McNally ◽  
Zhiyong Zong
Keyword(s):  
Klebsiella Pneumoniae ◽  
Southeast Asia ◽  
Human Blood ◽  
Sequence Type ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Transmissible Plasmid ◽  
Long Read

ABSTRACT A carbapenem-resistant Klebsiella pneumoniae isolate was recovered from human blood. Its whole-genome sequence was obtained using Illumina and long-read MinION sequencing. The strain belongs to sequence type 273 (ST273), which was found recently and caused an outbreak in Southeast Asia. It has two carbapenemase genes, bla NDM-1 (carried by an ST7 IncN self-transmissible plasmid) and bla IMP-4 (located on a self-transmissible IncHI5 plasmid). Non-KPC-producing ST237 may represent a lineage of carbapenem-resistant K. pneumoniae , which warrants further monitoring.

scholarly journals Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Ana M. Rada ◽  
Elsa De La Cadena ◽  
Carlos Agudelo ◽  
Cesar Capataz ◽  
Nataly Orozco ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Neonatal Intensive Care ◽  
Carbapenem Resistance ◽  
Health Interventions ◽  
Global Public Health ◽  
Public Health Interventions ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Long Read

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

scholarly journals National Prevalence of Resistance to Third-Generation Cephalosporins in Escherichia coli Isolates from Layer Flocks in France

2013 ◽  
Vol 57 (12) ◽  
pp. 6351-6353 ◽  
Author(s):  
Claire Chauvin ◽  
Laetitia Le Devendec ◽  
Eric Jouy ◽  
Maena Le Cornec ◽  
Sylvie Francart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Confidence Interval ◽  
Egg Production ◽  
Generation Cephalosporin ◽  
Gene Control ◽  
Third Generation ◽  
Content Type ◽  
E Coli ◽  
National Prevalence ◽  
Third Generation Cephalosporins

ABSTRACTResistance ofEscherichia colito third-generation cephalosporin (3GC) in fecal samples representative of French egg production was studied. The susceptibility to cefotaxime ofE. coliisolates obtained by culture on nonselective media was determined. Twenty-two nonsusceptible isolates were obtained (7.51%; 95% confidence interval, 4.49 to 10.54%), the majority of which came from young birds. Most isolates carried ablaCTX-M-1group gene, and a few carried ablaCMY-2-like gene. Control of 3GC resistance in laying hens is needed.

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