Novel Subclone of #Carbapenem-Resistant #Klebsiella pneumoniae Sequence Type 11 with Enhanced #Virulence and Transmissibility, #China (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research

Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China

Kai Zhou1, Tingting Xiao1, Sophia David1, Qin Wang, Yanzi Zhou, Lihua Guo, David Aanensen, Kathryn E. Holt, Nicholas R. Thomson, Hajo Grundmann2, Ping Shen2, and Yonghong Xiao2

Author affiliations: First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People’s Hospital); Shenzhen, China (K. Zhou); The Second Clinical Medical College of Jinan University, Shenzhen (K. Zhou); Zhejiang University, Hangzhou, China (T. Xiao, Q. Wang, Y. Zhou, L. Guo, P. Shen, Y. Xiao); Centre for Genomic Pathogen Surveillance, Cambridge, UK (S. David, D. Aanensen); University of Melbourne, Melbourne, Victoria, Australia (K.-E. Holt); London School of Hygiene and Tropical Medicine, London, UK (K.E. Holt, N.R. Thomson); Wellcome Trust Sanger Centre, Cambridge (N.R. Thomson); University of Freiburg, Freiburg, Germany (H. Grundmann).

 

Abstract

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; China.

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#Vaccine #Protection against #MDR #Klebsiella pneumoniae in a Nonhuman Primate Model of Severe #LRTI (MBio, abstract)

[Source: MBio, full page: (LINK). Abstract, edited.]

Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

Natalia Malachowa, Scott D. Kobayashi, Adeline R. Porter, Brett Freedman, Patrick W. Hanley, Jamie Lovaglio, Greg A. Saturday, Donald J. Gardner, Dana P. Scott, Amanda Griffin, Kathleen Cordova, Dan Long, Rebecca Rosenke, Daniel E. Sturdevant, Daniel Bruno, Craig Martens, Barry N. Kreiswirth, Frank R. DeLeo

Paul Keim, Editor

DOI: 10.1128/mBio.02994-19

 

ABSTRACT

Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types.

 

IMPORTANCE

Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Vaccines; Animal models.

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#XDR #Klebsiella pneumoniae ST307 #outbreak, north-eastern #Germany, June to October 2019 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019

Sebastian Haller1, Rolf Kramer1, Karsten Becker5, Jürgen A Bohnert5, Tim Eckmanns1, Jörg B Hans6, Jane Hecht1, Claus-Dieter Heidecke5, Nils-Olaf Hübner5, Axel Kramer5, Kathleen Klaper2, Martina Littmann4, Lennart Marlinghaus6, Bernd Neumann2, Yvonne Pfeifer2, Niels Pfennigwerth6, Simone Rogge4, Katharina Schaufler7, Andrea Thürmer3, Guido Werner2, Sören Gatermann6

Affiliations: 1 Robert Koch Institute, Department for Infectious Disease Epidemiology, Berlin, Germany; 2 Robert Koch Institute, Division of Nosocomial Pathogens and Antibiotic Resistance, Wernigerode, Germany; 3 Robert Koch Institute, Genome Sequencing Unit, Berlin, Germany; 4 Regional Public Health Authority Mecklenburg-Western Pomerania, Rostock, Germany; 5 University Medicine Greifswald, Greifswald, Germany; 6 National Reference Centre for multidrug-resistant Gram-negative bacteria, Ruhr University Bochum, Bochum, Germany; 7 Institute of Pharmacy, University of Greifswald, Greifswald, Germany

Correspondence:  Sebastian Haller

Citation style for this article: Haller Sebastian, Kramer Rolf, Becker Karsten, Bohnert Jürgen A, Eckmanns Tim, Hans Jörg B, Hecht Jane, Heidecke Claus-Dieter, Hübner Nils-Olaf, Kramer Axel, Klaper Kathleen, Littmann Martina, Marlinghaus Lennart, Neumann Bernd, Pfeifer Yvonne, Pfennigwerth Niels, Rogge Simone, Schaufler Katharina, Thürmer Andrea, Werner Guido, Gatermann Sören. Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. Euro Surveill. 2019;24(50):pii=1900734. https://doi.org/10.2807/1560-7917.ES.2019.24.50.1900734

Received: 03 Dec 2019;   Accepted: 12 Dec 2019

 

Abstract

From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Nosocomial outbreaks; Germany.

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A #cluster of #colistin- and #carbapenem-resistant #Klebsiella pneumoniae carrying #blaNDM-1 and #mcr-8.2 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

A cluster of colistin- and carbapenem-resistant Klebsiella pneumoniae carrying blaNDM-1 and mcr-8.2

Ke Ma, Yu Feng, Lu Liu, Zhihong Yao, Zhiyong Zong

The Journal of Infectious Diseases, jiz519, https://doi.org/10.1093/infdis/jiz519

Published: 11 December 2019

 

Abstract

Background

Klebsiella pneumoniae resistant to both carbapenems and colistin imposes severe challenges for management. Here we report a cluster of five carbapenem-resistant K. pneumoniae clinical strains belonging to ST1 and K57 types, four of which were also resistant to colistin, from two hospitals.

Methods

The five strains were subjected to whole genome sequencing (WGS) using the short-read Illumina HiSeq platform and two strains were also selected for long-read WGS using MinION. Clonal relatedness of the five strains was determined based on single nucleotide polymorphisms (SNPs). Conjugation experiments were performed to obtain self-transmissible plasmids.

Results

All five strains carried the carbapenemase-encoding gene blaNDM-1, whereas the four colistin-resistant strains also harbored a new variant of the mcr-8 colistin resistance gene, namely mcr-8.2. Mcr-8.2 differs from Mcr-8.1 by four amino acid substitutions (A51V, A232S, N365Y, and N480K). mcr-8.2 was located on a large, hybrid, non-self-transmissible plasmid containing IncQ, IncR, and IncFII replicons, whereas blaNDM-1 was carried by self-transmissible IncX3 plasmids. Phylogenetic analysis based on SNPs revealed that the five strains were likely to have a common origin.

Conclusion

Both the intra- and inter-hospital transfer of strains carrying mcr-8 and blaNDM-1 were identified, which represents an emerging threat for clinical management and infection control.

colistin resistance, mcr, plasmid, Klebsiella pneumoniae

Topic: plasmids – colistin – klebsiella pneumoniae – single nucleotide polymorphism – beta-lactamase ndm-1 – carbapenem resistance – whole genome sequencing

This content is only available as a PDF.

Author notes: These authors contributed equally.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Colistin; Carbapenem; Klebsiella pneumoniae; Nosocomial outbreaks; NDM1.

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Successful rescue #treatment of #sepsis due to a #PDR, #NDM-producing #Klebsiella pneumoniae using #aztreonam powder for nebulizer solution as IV therapy in combination with #ceftazidime/avibactam (J Antimicrob Chemother., summary)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Summary, edited.]

Successful rescue treatment of sepsis due to a pandrug-resistant, NDM-producing Klebsiella pneumoniae using aztreonam powder for nebulizer solution as intravenous therapy in combination with ceftazidime/avibactam

Elske Sieswerda, Marre van den Brand, Roland B van den Berg, Joris Sträter, Leo Schouls, Karin van Dijk, Andries E Budding

Journal of Antimicrobial Chemotherapy, dkz495, https://doi.org/10.1093/jac/dkz495

Published: 02 December 2019

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Sir,

Pandrug-resistant Klebsiella pneumoniae that produces New Delhi MBL (NDM) is increasingly reported worldwide.1 These strains contain multiple β-lactamase genes but also may have acquired resistance to last-resort options such as colistin and tigecycline. Combining aztreonam and avibactam is potentially effective in MDR, NDM-producing Enterobacterales.2 Avibactam inhibits class A, C and D ESBLs, cephalosporinases and carbapenemases, while aztreonam is stable to hydrolysis by class B MBLs such as NDM. Until this drug combination becomes available, one could combine aztreonam and ceftazidime/avibactam to treat serious infections with such strains. A small number of studies have reported on 13 patients with serious infections with NDM-producing Enterobacterales who were successfully treated with aztreonam and ceftazidime/avibactam.3–7 Evidence of clinical efficacy and safety is therefore limited at present. Also, aztreonam for IV use is not registered and readily available in many countries, including the Netherlands. We describe successful rescue treatment of a patient with sepsis due to a pandrug-resistant, NDM-producing K. pneumoniae using aztreonam powder for nebulizer solution as IV therapy in combination with ceftazidime/avibactam.

(…)

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Acknowledgements

We presented this study in March 2019 at the Scientific Spring Meeting 2019 from the Dutch Society of Medical Microbiology, Arnhem, the Netherlands.

Funding

This study was carried out as part of our routine work.

Transparency declarations

None to declare.

Keywords: Antibiotics; Drugs Resistance; NDM; Klebsiella pneumoniae; Sepsis; Aztreonam; Ceftazidime; Avibactam.

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Do #vegetarians less frequently carry #ESBL/pAmpC-producing #Escherichia coli/Klebsiella pneumoniae compared with non-vegetarians? (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Do vegetarians less frequently carry ESBL/pAmpC-producing Escherichia coli/Klebsiella pneumoniae compared with non-vegetarians?

Anouk P Meijs, Esther F Gijsbers, Paul D Hengeveld, Christiaan Veenman, Annika M van Roon, Angela H A M van Hoek, Sabine C de Greeff, Engeline van Duijkeren, Cindy M Dierikx

Journal of Antimicrobial Chemotherapy, dkz483, https://doi.org/10.1093/jac/dkz483

Published: 25 November 2019

 

Abstract

Background

ESBL and plasmid-mediated AmpC (pAmpC)-producing Enterobacteriaceae are frequently found on meat products in Dutch retail, especially on poultry.

Objectives

We investigated whether vegetarians are at lower risk of carrying ESBL/pAmpC-producing Escherichia coli/Klebsiella pneumoniae (ESBL-E/K) compared with persons who consume meat.

Methods

Vegetarians, pescatarians (vegetarians who eat fish) and non-vegetarians (persons who eat meat at least three times per week) were asked to send in a faecal sample and a questionnaire. ESBL-E/K were cultured and MLSTs were determined. ESBL/pAmpC genes were analysed using PCR and sequencing. The risk of ESBL-E/K carriage in the three study groups was analysed using multivariable logistic regression.

Results

Prevalence of ESBL-E/K carriage was 8.0% in vegetarians (63/785; 95% CI 6.3–10.1), 6.9% in pescatarians (27/392; 95% CI 4.8–9.8) and 3.8% in non-vegetarians (14/365; 95% CI 2.3–6.3). Multivariable analysis showed an OR for ESBL-E/K carriage of 2.2 for vegetarians (95% CI 1.2–4.0) and 1.6 for pescatarians (95% CI 0.8–3.2) compared with non-vegetarians. The predominant MLST was E. coli ST131 and the most common ESBL genes were blaCTX-M-15, blaCTX-M-27, blaCTX-M-14 and blaCTX-M-1 in all diet groups. Independent risk factors for ESBL-E/K carriage were travel to Africa/Latin America/Asia (OR 4.6; 95% CI 2.8–7.7) in the past 6 months and rarely/never washing hands before food preparation (OR 2.5; 95% CI 1.2–5.0).

Conclusions

Vegetarians and pescatarians did not have a lower risk of ESBL-E/K carriage compared with non-vegetarians, indicating that eating meat is not an important risk factor for ESBL-E/K carriage.

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; E. Coli; Klebsiella pneumoniae; Food Safety.

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#Evolution of #hypervirulence in #carbapenem-resistant #Klebsiella pneumoniae in #China: a multicentre, molecular epidemiological analysis (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis

Yawei Zhang, Longyang Jin, Pengwen Ouyang, Qi Wang, Ruobing Wang, Juan Wang, Hua Gao, Xiaojuan Wang, Hui Wang on behalf of the China Carbapenem-Resistant Enterobacteriaceae (CRE) Network

Journal of Antimicrobial Chemotherapy, dkz446, https://doi.org/10.1093/jac/dkz446

Published: 12 November 2019

 

Abstract

Objectives

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described.

Methods

We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated.

Results

A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P = 0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P = 0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid.

Conclusions

CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Plasmids; China.

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