scholarly journals Ten years of population-level genomic Escherichia coli and Klebsiella pneumoniae serotype surveillance informs vaccine development for invasive infections

2020 ◽  
Author(s):  
Samuel Lipworth ◽  
Karina-Doris Vihta ◽  
Kevin K Chau ◽  
James Kavanagh ◽  
Timothy Davies ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vaccine Development ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Population Level ◽  
Small Subset ◽  
Invasive Infections ◽  
Common Serotypes ◽  
O Antigens

The incidence of bloodstream infections (BSIs) caused by Enterobacteriaceae (e.g. Escherichia coli, Klebsiella pneumoniae) continues to increase globally and the threat of untreatable disease is substantial1. Prophylactic vaccines represent an alternative approach to combating antimicrobial resistance (AMR) by reducing antibiotic usage and preventing infections caused by AMR-associated strains. To investigate their potential utility, we performed in silico serotyping on 4035 E. coli/K. pneumoniae BSI from population-level surveillance in Oxfordshire (2008-2018) in addition to 3678 isolates from previous studies. Most infections, including those associated with AMR, were caused by isolates with a small subset of O-antigens, with no evidence that the proportion of BSIs caused by these changed significantly over time. O-antigen targeted vaccines might therefore be useful in reducing the significant morbidity and mortality2 associated with BSIs. Vaccines may also have a role in preventing the spread of carbapenem resistance genes into common serotypes associated with community-onset disease.

scholarly journals High Prevalence of Hypervirulent Klebsiella pneumoniae Infection in China: Geographic Distribution, Clinical Characteristics, and Antimicrobial Resistance

2016 ◽  
Vol 60 (10) ◽  
pp. 6115-6120 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Geographic Distribution ◽  
Virulence Gene ◽  
Bloodstream Infections ◽  
Systemic Steroid ◽  
Content Type ◽  
Invasive Infections ◽  
Clinical Awareness ◽  
Abdominal Infections

ABSTRACTHypervirulentKlebsiella pneumoniae(hvKP) is traditionally defined by hypermucoviscosity, but data based on genetic background are limited. Antimicrobial-resistant hvKP has been increasingly reported but has not yet been systematically studied.K. pneumoniaeisolates from bloodstream infections, hospital-acquired pneumonia, and intra-abdominal infections were collected from 10 cities in China during February to July 2013. Clinical data were collected from medical records. AllK. pneumoniaeisolates were investigated by antimicrobial susceptibility testing, string test, extended-spectrum β-lactamase (ESBL) gene detection, capsular serotypes, virulence gene profiles, and multilocus sequence typing. hvKP was defined by aerobactin detection. Of 230K. pneumoniaeisolates, 37.8% were hvKP. The prevalence of hvKP varied among different cities, with the highest rate in Wuhan (73.9%) and the lowest in Zhejiang (8.3%). Hypermucoviscosity and the presence of K1, K2, K20, andrmpAgenes were strongly associated with hvKP (P< 0.001). A significantly higher incidence of liver abscess (P= 0.026), sepsis (P= 0.038), and invasive infections (P= 0.043) was caused by hvKP. Cancer (odds ratio [OR], 2.285) and diabetes mellitus (OR, 2.256) appeared to be independent variables associated with hvKP infections by multivariate analysis. Importantly, 12.6% of hvKP isolates produced ESBLs, and most of them carriedblaCTX-Mgenes. Patients with neutropenia (37.5% versus 5.6%;P= 0.020), history of systemic steroid therapy (37.5% versus 5.6%;P= 0.020), and combination therapy (62.5% versus 16.7%;P= 0.009) were more likely to be infected with ESBL-producing hvKP. The prevalence of hvKP is high in China and has a varied geographic distribution. ESBL-producing hvKP is emerging, suggesting an urgent need to enhance clinical awareness, especially for immunocompromised patients receiving combination therapy.

scholarly journals Carbapenem resistance in Escherichia coli and Klebsiella pneumoniae among Indian and international patients in North India

2019 ◽  
Vol 66 (3) ◽  
pp. 367-376
Author(s):  
Namita Jaggi ◽  
Nirupama Chatterjee ◽  
Vyoma Singh ◽  
Santosh Kumar Giri ◽  
Priyambada Dwivedi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
North India

scholarly journals 1047. Global Surveillance: Susceptibility of Ceftolozane–Tazobactam Against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa Isolates Collected From Bloodstream Infections in the United States From 2015 to 2017

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S313-S313
Author(s):  
S J Ryan Arends ◽  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Robert K Flamm
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Bloodstream Infections ◽  
The United States ◽  
Research Support ◽  
Broth Microdilution Method ◽  
The Us ◽  
Tract Infections

Abstract Background Ceftolozane–tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors Gram-negative (GN) isolates resistant to C-T worldwide. In the current study, isolates were collected from patients hospitalized with bloodstream infections (BSIs) from 2015 to 2017 within the United States. Methods A total of 3,377 prevalence-based BSI GN isolates, including Escherichia coli (EC; 1,422), Klebsiella pneumoniae (KPN, 630), and Pseudomonas aeruginosa (PSA; 344), were collected during 2015 to 2017 from 32 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP). Antibiotic-resistant phenotypes analyzed (CLSI, 2018) for EC and KPN included carbapenem-R (CR) and non-CR extended-spectrum β-lactamase (ESBL); as well as CAZ-nonsusceptible (CAZ-NS), MEM-NS, and COL-NS PSA. Results Of the 3,377 BSI GN isolates, 3,219 (95.3%) had a C-T MIC ≤ 4 mg/L. The three most prevalent GN species isolated from BSIs were EC (42.1%), KPN (18.7%), and PSA (10.2%). The %S of C-T and comparators for the top three pathogens are shown in the table. C-T showed activity against these isolates with %S of ≥96.0% against all three species. Of the comparators tested, AMK and COL also had high %S against these isolates. Conclusion C-T demonstrated activity against the most prevalent contemporary GN isolates from BSIs in the US. C-T was the only beta-lactam that had ≥96%S against all three species: EC, KPN, and PSA. For PSA, C-T maintained activity (&gt;90%S) against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN BSI. Disclosures S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. M. Castanheira, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.

scholarly journals Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Willames M. B. S. Martins ◽  
Marisa F. Nicolas ◽  
Yang Yu ◽  
Mei Li ◽  
Priscila Dantas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Illumina Miseq ◽  
Clinical Analysis ◽  
High Copy Number ◽  
Health Concern ◽  
Helper Plasmid ◽  
Content Type

ABSTRACT This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolates were further analyzed by Nanopore MinION sequencing, allowing complete chromosome and plasmid circularization (hybrid assembly), using Unicycler software. The clinical analysis showed that the 30-day overall mortality for these BSI cases was high (83%). The isolates exhibited meropenem resistance (MICs, 32 to 128 mg/liter), with 3/6 isolates resistant to polymyxin B. The conjugative properties of the blaKPC-2 plasmid and its copy number were assessed by standard conjugation experiments and sequence copy number analysis. We identified in all six isolates a small (8.3-kb), high-copy-number (20 copies/cell) non-self-conjugative IncQ plasmid harboring blaKPC-2 in a non-Tn4401 transposon. This plasmid backbone was previously reported to harbor blaKPC-2 only in Brazil, and it could be comobilized at a high frequency (10−4) into Escherichia coli J53 and into several high-risk K. pneumoniae clones (ST258, ST15, and ST101) by a common IncL/M helper plasmid, suggesting the potential of international spread. This study thus identified the international K. pneumoniae ST15 clone as a carrier of blaKPC-2 in a high-copy-number IncQ1 plasmid that is easily transmissible among other common Klebsiella strains. This finding is of concern since IncQ1 plasmids are efficient antimicrobial resistance determinant carriers across Gram-negative species. The spread of such carbapenemase-encoding IncQ1 plasmids should therefore be closely monitored. IMPORTANCE In many parts of the world, carbapenem resistance is a serious public health concern. In Brazil, carbapenem resistance in Enterobacterales is mostly driven by the dissemination of KPC-2-producing K. pneumoniae clones. Despite being endemic in this country, only a few reports providing both clinical and genomic data are available in Brazil, which limit the understanding of the real clinical impact caused by the dissemination of different clones carrying blaKPC-2 in Brazilian hospitals. Although several of these KPC-2-producer K. pneumoniae isolates belong to the clonal complex 258 and carry Tn4401 transposons located on large plasmids, a concomitant emergence and silent dissemination of small high-copy-number blaKPC-2 plasmids are of importance, as described in this study. Our data identify a small high-copy-number IncQ1 KPC plasmid, its clinical relevance, and the potential for conjugative transfer into several K. pneumoniae isolates, belonging to different international lineages, such as ST258, ST101, and ST15.

KPC-2 carbapenemase and DHA-1 AmpC determinants carried on the same plasmid in Enterobacter aerogenes

2014 ◽  
Vol 63 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Shougang Kuai ◽  
Haifeng Shao ◽  
Lihua Huang ◽  
Hao Pei ◽  
Zhonghua Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Clinical Isolate ◽  
Southern Blotting ◽  
Antimicrobial Agents ◽  
Resistance Mechanism ◽  
Enterobacter Aerogenes ◽  
Carbapenem Resistance ◽  
Jiangsu Province ◽  
Republic Of China

This study was conducted to analyse the presence of a plasmid-mediated carbapenem resistance mechanism in a clinical Enterobacter aerogenes isolate from a patient from Jiangsu province, People’s Republic of China. PCR and sequencing confirmed that the isolate harboured Klebsiella pneumoniae carbapenemase (KPC)-2, DHA-1 and TEM-1 β-lactamase genes. Both the KPC-2 and DHA-1 genes were transferred to Escherichia coli C600 by transconjugation, and Southern blotting confirmed that these two genes were located on the same plasmid, which was of approximately 56 kb in size. The Enterobacter aerogenes isolate was resistant to carbapenems and other tested antimicrobial agents. The Escherichia coli transconjugant showed reduced susceptibility but not resistance to carbapenems and other β-lactams, indicating the presence of another, possibly permeability-related, resistance mechanism in the clinical isolate.

scholarly journals Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli Isolates Possessing the Plasmid-Mediated Carbapenem-Hydrolyzing β-Lactamase KPC-2 in Intensive Care Units of a Chinese Hospital

2008 ◽  
Vol 52 (6) ◽  
pp. 2014-2018 ◽  
Author(s):  
Jia Chang Cai ◽  
Hong Wei Zhou ◽  
Rong Zhang ◽  
Gong-Xiang Chen
Keyword(s):  
Escherichia Coli ◽  
Intensive Care ◽  
Klebsiella Pneumoniae ◽  
Serratia Marcescens ◽  
Intensive Care Units ◽  
Gel Electrophoresis ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
E Coli ◽  
Insertional Inactivation

ABSTRACT Twenty-one Serratia marcescens, ten Klebsiella pneumoniae, and one Escherichia coli isolate with carbapenem resistance or reduced carbapenem susceptibility were recovered from intensive care units (ICUs) in our hospital. Enterobacterial repetitive intergenic consensus-PCR and pulsed-field gel electrophoresis demonstrated that all the S. marcescens isolates belonged to a clonal strain and the 10 K. pneumoniae isolates were indistinguishable or closely related to each other. The MICs of imipenem, meropenem, and ertapenem for all isolates were 2 to 8 μg/ml, except for K. pneumoniae K10 (MICs of 128, 256, and >256 μg/ml). Isoelectric focusing, PCRs, and DNA sequencing indicated that all S. marcescens isolates produced KPC-2 and a β-lactamase with a pI of 6.5. All K. pneumoniae isolates produced TEM-1, KPC-2, CTX-M-14, and a β-lactamase with a pI of 7.3. The E. coli E1 isolate produced KPC-2, CTX-M-15, and a β-lactamase with a pI of 7.3. Conjugation studies with E. coli (EC600) resulted in the transfer of reduced carbapenem susceptibility compared to that of the original isolates, and only the bla KPC-2 gene was detected in E. coli transconjugants. Plasmid restriction analysis showed identical restriction patterns among all E. coli transconjugants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ompK35/36 gene sequence analysis of outer membrane proteins revealed that K. pneumoniae K10 failed to express OmpK36, because of insertional inactivation by an insertion sequence ISEcp1. All these results indicate that KPC-2-producing S. marcescens, K. pneumoniae, and E. coli isolates emerged in ICUs in our hospital. KPC-2 combined with porin deficiency results in high-level carbapenem resistance in K. pneumoniae. The same bla KPC-2-encoding plasmid was spread among the three different genera.

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