#NDM-β-Lactamase-5–Producing #Escherichia coli in Companion #Animals, #USA (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 Letter

New Delhi Metallo-β-Lactamase-5–Producing Escherichia coli in Companion Animals, United States

Stephen D. Cole, Laura Peak, Gregory H. Tyson, Renate Reimschuessel, Olgica Ceric, and Shelley C. Rankin

Author affiliations: University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA (S.D. Cole, S.C. Rankin); Louisiana State University, Baton Rouge, Louisiana USA (L. Peak); US Food and Drug Administration, Silver Spring, Maryland, USA (G.H. Tyson, R. Reimscheussel, O. Ceric)

 

Abstract

We report isolation of a New Delhi metallo-β-lactamase-5–producing carbapenem-resistant Escherichia coli sequence type 167 from companion animals in the United States. Reports of carbapenem-resistant Enterobacteriaceae in companion animals are rare. We describe a unique cluster of blaNDM-5–producing E. coli in a veterinary hospital.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; NDM1; USA.

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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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Restoring #colistin sensitivity in colistin-resistant #Ecoli: Combinatorial use of MarR inhibitor with efflux pump inhibitor (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Dec 25;9(1):19845. doi: 10.1038/s41598-019-56325-x.

Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor.

Sundaramoorthy NS1, Suresh P2, Selva Ganesan S2, GaneshPrasad A1, Nagarajan S3.

Author information: 1 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 2 Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 3 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. sai@scbt.sastra.edu.

 

Abstract

Antibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. In this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo.

PMID: 31882661 DOI: 10.1038/s41598-019-56325-x

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Colistin; Enterobacteriaceae.

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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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#Carbapenem-Resistant Gram-Negative #Infections in #Children (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Carbapenem-Resistant Gram-Negative Infections in Children.

David Aguilera-Alonso, Luis Escosa-García, Jesús Saavedra-Lozano, Emilia Cercenado, Fernando Baquero-Artigao

DOI: 10.1128/AAC.02183-19

 

ABSTRACT

Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales through carbapenemase production hydrolyze almost all β-lactams. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved. Some of them (e.g., plazomicin or imipenem-cilastatin-relebactam) are currently only approved for adults; others (e.g., ceftazidime-avibactam) have recently been approved for children. Recommendations for antibiotic therapy of CRO infections in pediatric patients are based on evidence mainly from adult studies. The availability of pediatric pharmacokinetics and safety data is the cornerstone to broaden the use of proposed agents in adults to the pediatric population. This article provides a comprehensive review of the current knowledge regarding infections caused by CRO with a focus on children which includes epidemiology, risk factors, outcomes and antimicrobial therapy management, with particular attention to new antibiotics.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Gram-negative bacteria; Pediatrics.

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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

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Author notes: These authors contributed equally.

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

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