Reduced #ceftazidime and #ertapenem susceptibility due to production of #OXA-2 in #Klebsiella pneumoniae ST258 (J Antimicrob Chemother., abstract)

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

Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniaeST258

Alina Iovleva, Roberta T Mettus, Christi L McElheny, Mustapha M Mustapha, Daria Van Tyne, Ryan K Shields, A William Pasculle, Vaughn S Cooper, Yohei Doi

Journal of Antimicrobial Chemotherapy, dkz183, https://doi.org/10.1093/jac/dkz183

Published: 24 May 2019

 

Abstract

Background

OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2.

Objectives

To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate.

Methods

MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT–PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in β-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme.

Results

K. pneumoniae 1761 belonged to ST258 and carried both blaKPC-2 and blaOXA-2. However, expression of blaKPC-2 was substantially reduced due to an IS1294insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying blaOXA-2-harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. blaOXA-2 was carried on a 2910 bp partial class 1 integron containing aacA4-blaOXA-2-qacEΔ1-sul1 on an IncA/C2plasmid, which was not present in the earlier ST258 isolates possessing blaKPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme.

Conclusions

Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.

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; Beta-lactams; Carbapenem; Ceftazidime; Ertapenem; Meropenem; Imipenem; Cefepime.

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Emergence of #NDM1-producing #Klebsiella pneumoniae in #Greece: evidence of a #widespread clonal #outbreak (J Antimicrob Chemother., abstract)

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

Emergence of NDM-1-producing Klebsiella pneumoniae in Greece: evidence of a widespread clonal outbreak

Lida Politi, Konstantina Gartzonika, Nicholas Spanakis, Olympia Zarkotou, Aggeliki Poulou, Lemonia Skoura, Georgia Vrioni, Athanasios Tsakris

Journal of Antimicrobial Chemotherapy, dkz176, https://doi.org/10.1093/jac/dkz176

Published: 07 May 2019

 

Abstract

Objectives

NDM-producing Enterobacteriaceae clinical isolates remain uncommon in the European region. We describe the emergence and broad dissemination of one successful NDM-1-producing Klebsiella pneumoniae clone in Greek hospitals.

Methods

During a 4 year survey (January 2013–December 2016), 480 single-patient carbapenem non-susceptible K. pneumoniae isolates, phenotypically MBL positive, were consecutively recovered in eight Greek hospitals from different locations and subjected to further investigation. Antimicrobial susceptibility testing, combined-disc test, identification of resistance genes by PCR and sequencing, molecular fingerprinting by PFGE, plasmid profiling, replicon typing, conjugation experiments and MLST were performed.

Results

Molecular analysis confirmed the presence of the blaNDM-1 gene in 341 (71%) K. pneumoniae isolates. A substantially increasing trend of NDM-1-producing K. pneumoniae was noticed during the survey (R2 = 0.9724). Most blaNDM-1-carrying isolates contained blaCTX-M-15, blaOXA-1, blaOXA-2 and blaTEM-1genes. PFGE analysis clustered NDM-1 producers into five distinct clonal types, with five distinct STs related to each PFGE clone. The predominant ST11 PFGE clonal type was detected in all eight participating hospitals, despite adherence to the national infection control programme; it was identical to that observed in the original NDM-1 outbreak in Greece in 2011, as well as in a less-extensive NDM-1 outbreak in Bulgaria in 2015. The remaining four ST clonal types (ST15, ST70, ST258 and ST1883) were sporadically detected. blaNDM-1 was located in IncFII-type plasmids in all five clonal types.

Conclusions

This study gives evidence of possibly the largest NDM-1-producing K. pneumoniae outbreak in Europe; it may also reinforce the hypothesis of an NDM-1 clone circulating in the Balkans.

Topic: polymerase chain reaction – plasmids – carbapenem – bulgaria – clone cells – disease outbreaks – electrophoresis, gel, pulsed-field – enterobacteriaceae – genes – greece – ichthyosis, x-linked – infectious disease prevention / control – klebsiella pneumoniae  – replicon – sequence tagged sites – sodium thiosulfate – antimicrobial susceptibility test – beta-lactamase ndm-1 – resistance genes – molecular profiling

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; Carbapene; NDM1; Klebsiella pneumoniae; Greece; Nosocomial outbreaks.

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Identification of a #Carbapenemase-Producing #Hypervirulent #Klebsiella pneumoniae Isolate, #USA (Antimicrob Agents Chemother., abstract)

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

Identification of a Carbapenemase-Producing Hypervirulent Klebsiella pneumoniae Isolate, United States

Maria Karlsson, Richard A. Stanton, Uzma Ansari, Gillian McAllister, Monica Y. Chan, Erisa Sula, Julian E. Grass, Nadezhda Duffy, Melissa L. Anacker, Medora L. Witwer, J. Kamile Rasheed,Christopher A. Elkins, Alison Laufer Halpin

DOI: 10.1128/AAC.00519-19

 

ABSTRACT

We report on a carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-hvKP) collected from a U.S. patient at an outpatient clinic. The isolate was identified as K. pneumoniae serotype K1, sequence type 23 and included both a hypervirulence (with rmpA, rmpA2 iroBCDN, peg-344 and iucABCD-iutA genes) and a carbapenemase-encoding (blaKPC-2) plasmid. The emergence of CP-hvKP underscores the importance of clinical awareness of this pathotype and the need for continued monitoring of CP-hvKP in the United States.

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Keywords: Antibiotics; Drugs Resistance; Carbapenen; Klebsiella pneumoniae; Plasmids; USA.

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Effect of #carbapenem #resistance on outcomes of #bloodstream #infection caused by #Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study

Andrew J Stewardson, MBBS  †, Kalisvar Marimuthu, MBBS †, Sharmila Sengupta, MD, Arthur Allignol, PhD, Maisra El-Bouseary, PhD, Maria J Carvalho, PhD, Brekhna Hassan, PhD, Monica A Delgado-Ramirez, MD, Anita Arora, MD, Ruchika Bagga, MD, Alex K Owusu-Ofori, MD, Joseph O Ovosi, MBBS, Shamsudin Aliyu, MBBS, Hala Saad, MD, Prof Souha S Kanj, MD, Prof Basudha Khanal, MD, Prof Balkrishna Bhattarai, MD, Samir K Saha, PhD, Jamal Uddin, MPH, Purabi Barman, MD, Latika Sharma, MD, Tarek El-Banna, PhD, Rabaab Zahra, PhD, Mansab Ali Saleemi, MPhil, Amarjeet Kaur, MD, Kenneth Iregbu, FWACP, Nkolika SC Uwaezuoke, FWACP, Pierre Abi Hanna, MD, Rita Feghali, MD, Prof Ana L Correa, MD, Maria I Munera, MD, Thi Anh Thu Le, MD, Thi Thanh Nga Tran, MD, Chimanjita Phukan, MD, Chiranjita Phukan, MD, Sandra L Valderrama-Beltrán, MD, Prof Carlos Alvarez-Moreno, MD, Prof Timothy R Walsh, DSc, Prof Stephan Harbarth, MD

Published: April 29, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30792-8

 

Summary

Background

Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae.

Methods

The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis.

Findings

Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades.

Interpretation

Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs.

Funding

bioMérieux.

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

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#Reversal of #carbapenemase-producing #Klebsiella pneumoniae #epidemiology from blaKPC- to blaVIM-harbouring isolates in a #Greek #ICU after introduction of #ceftazidime/avibactam (J Antimicrob Chemother., abstract)

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

Reversal of carbapenemase-producing Klebsiella pneumoniae epidemiology from blaKPC- to blaVIM-harbouring isolates in a Greek ICU after introduction of ceftazidime/avibactam

Matthaios Papadimitriou-Olivgeris, Christina Bartzavali, Anastasia Lambropoulou, Anastasia Solomou, Ekaterini Tsiata, Evangelos D Anastassiou, Fotini Fligou, Markos Marangos, Iris Spiliopoulou, Myrto Christofidou

Journal of Antimicrobial Chemotherapy, dkz125, https://doi.org/10.1093/jac/dkz125

Published: 19 April 2019

 

Abstract

Objectives

Our aim was to determine the epidemiology of bloodstream infections (BSIs) by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) after the introduction of ceftazidime/avibactam in January 2018 among ICU patients.

Patients and methods

All patients hospitalized at the ICU of the University General Hospital of Patras, Greece with CP-Kp BSI during 2015–18 were included. MICs of meropenem, fosfomycin, tigecycline and ceftazidime/avibactam (only for isolates from 2018) were determined by Etest, whereas for colistin, the broth microdilution method was applied. All isolates were tested by PCR for the presence of blaKPC, blaVIM, blaNDM and blaOXA-48 genes.

Results

Among 170 BSIs due to CP-Kp (2015–18), 132 (78%) were caused by isolates carrying blaKPC (4 ceftazidime/avibactam-resistant), 17 blaVIM (10%), 16 blaNDM (9%) and 5 carrying both blaKPC and blaVIM (3%). From 2015 to 2017 (125 BSIs), KPC-producing strains (110; 88%) predominated, followed by NDM-producing strains (15; 12%), whereas no VIM-producing strain was isolated. Among the 45 BSIs in 2018, 22 (49%) were due to isolates carrying blaKPC (4 ceftazidime/avibactam resistant), followed by 17 (38%) carrying blaVIM, 5 (11%) carrying both blaKPC and blaVIM, and 1 isolate carrying blaNDM (2%). MBLs were more frequent in 2018 compared with 2015–17 (51% versus 12%; P < 0.001). Multivariate analysis found that prior administration of ceftazidime/avibactam (P = 0.014; OR 16.7, 95% CI 1.8–158.6) was independently associated with the development of BSI due to ceftazidime/avibactam-resistant isolates.

Conclusions

Widespread ceftazidime/avibactam use may lead to a change in the palette of carbapenemases by replacing KPC with MBL-producing isolates.

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; Ceftazidime; Avibactam; NDM; ICU; Greece; Klebsiella pneumoniae.

——

#SME-4-producing #Serratia marcescens from #Argentina belonging to clade 2 of the S. marcescens phylogeny (J Antimicrob Chemother., abstract)

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

SME-4-producing Serratia marcescens from Argentina belonging to clade 2 of the S. marcescens phylogeny

Laura Dabos, Rafael Patiño-Navarrete, Marcela Nastro, Angela Famiglietti, Philippe Glaser, Carlos H Rodriguez, Thierry Naas

Journal of Antimicrobial Chemotherapy, dkz115, https://doi.org/10.1093/jac/dkz115

Published: 16 April 2019

 

Abstract

Background

SME carbapenemases are increasingly reported, especially from North and South America. Here, we describe an SME-4-producing Serratia marcescens(SME-Sm) clinical isolate from Argentina and compare its genome with other SME-Sm and Sm isolates recovered from public databases.

Methods

Sm isolates were characterized by WGS using Illumina technology, susceptibility testing and MIC determination. Carbapenemase activity was revealed by biochemical tests based on imipenem hydrolysis. A whole-genome phylogeny was estimated for all the Sm isolates retrieved from public databases with kSNP3 and a whole-genome phylogenetic analysis based on non-recombinant core SNPs was inferred for Sm complete genomes and for those encoding any blaSME variants.

Results

Sm163 was resistant to amoxicillin, temocillin, aztreonam and carbapenems, remaining susceptible to extended-spectrum cephalosporins. WGS analysis of Sm163 revealed a genome of 5 139 329 bp and a chromosomally encoded blaSME-4 carbapenemase gene located on a genomic island closely related to SmarGI1-1 of Sm N11-02820. Comparison of the Sm genomes revealed that the 14 SME-Sm isolates possess this genomic island inserted at the same loci, that 13/14 belong to clade 1 and that 11/14 form a well-defined subcluster of cluster I of Sm clade 1, while Sm163 belongs to clade 2, suggesting that an SME-encoding genomic island may have been transferred between isolates from different clades.

Conclusions

To the best of our knowledge this is the first report of an SME-4-encoding Smfrom Argentina. The blaSME-4 gene is located on a SmarGI1-1-like genomic island. The genome of Sm163 belongs to clade 2, unlike all the other SME-Smisolates, which belong to clade 1.

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; Carbapene; Serratia marcescens; Amoxicillin; Temocillin; Aztreonam; Argentina.

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#OXA-48-producing #Enterobacterales in different ecological niches in #Algeria: clonal expansion, #plasmid characteristics and #virulence traits (J Antimicrob Chemother., abstract)

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

OXA-48-producing Enterobacterales in different ecological niches in Algeria: clonal expansion, plasmid characteristics and virulence traits

Assia Mairi, Alix Pantel, Farès Ousalem, Albert Sotto, Abdelaziz Touati, Jean-Philippe Lavigne

Journal of Antimicrobial Chemotherapy, dkz146, https://doi.org/10.1093/jac/dkz146

Published: 16 April 2019

 

Abstract

Objectives

To investigate the prevalence and molecular characteristics of OXA-48-carbapenemase-producing Enterobacterales strains recovered from various ecological niches in Algeria.

Methods

In total, 3309 samples were collected from different ecological niches (human carriage, animal farms, wild animals, pets, food products, aquatic environment and wastewater treatment plants) distributed among six provinces in Algeria between December 2015 and April 2017. The potential presence of OXA-48-producing Enterobacterales isolates was screened on selective medium. Resistance and virulence profiles were characterized by PCR and sequencing. The clonal relatedness of the different isolates was studied using Rep-PCR and MLST. Conjugation was performed for all OXA-48-producing isolates. The plasmids were analysed by PCR-based replicon typing and WGS.

Results

A total of 78 OXA-48-producing Enterobacterales isolates were detected from 3309 samples (2.4%). OXA producers were observed in all the screened sources. The blaCTX-M-15 gene was only observed in two isolates. Clonality analysis revealed distinct lineages of the isolates and a clonal expansion of Klebsiella pneumoniae ST13. K. pneumoniae and Escherichia coli had few virulence factors. Plasmid analysis confirmed that all the isolates harboured a very similar transferable plasmid (belonging to IncL) with a similar structure to the pOXA-48a plasmid carried by K. pneumoniae strain Kp11978.

Conclusions

This study suggests a global dissemination of OXA-48-producing Enterobacterales in different niches due mainly to the spread of an epidemic plasmid. Furthermore, it clearly shows that K. pneumoniae and commensal E. coli can be reservoirs of the blaOXA-48 gene, contributing to the dissemination and transfer of this gene to diverse bacteria among different sources.

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; Enterobacter spp.; Klebsiella pneumoniae; Algeria.

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