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Increasing incidence of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Belgian hospitals

Authors:
Morgane de Laveleye at Catholic University of Louvain
Morgane de Laveleye
Te-Din Huang at Centre Hospitalier Universitaire Mont-Godinne
Te-Din Huang
Pierre Bogaerts at Catholic University of Louvain
Pierre Bogaerts
C. Berhin
C. Berhin
C. Berhin
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Abstract

Carbapenemase-producing Enterobacteriaceae are increasingly reported worldwide. The aim of the study was to determine the incidence and molecular epidemiology of carbapenemase-producing (CP) Escherichia coli and Klebsiella pneumoniae (CP-E/K) in Belgium. Eleven hospital-based laboratories collected carbapenem non-susceptible (CNS) isolates of E. coli and K. pneumoniae detected in clinical specimens from January 2013 to December 2014. All CNS strains were tested for carbapenemase production and typed by multilocus sequence typing (MLST) for a 6-month period as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae in Europe (EuSCAPE) structured survey. In addition, an equal number of carbapenem-susceptible isolates collected were preserved as a control group for risk factor analysis. The overall incidence rate of CP-E/K isolates in hospitals increased from 0.124 in 2013 to 0.223 per 1000 admissions in 2014. From November 2013 to April 2014, 30 CP K. pneumoniae [OXA-48 (n = 16), KPC (n = 13), OXA-427 (n = 1)] and five CP E. coli [OXA-48 (n = 3), NDM (n = 1), OXA-427 (n = 1)] isolates were detected in ten hospitals. The 16 OXA-48-producing K. pneumoniae strains were distributed into eight sequence types (STs), while the 13 KPC-producing K. pneumoniae clustered into three STs dominated by ST512 (n = 7) and ST101 (n = 5). Compared to controls, we observed among CP-E/K carriers significantly higher proportion of males, respiratory origins, previous hospitalization, nosocomial setting, and a significantly lower proportion of bloodstream infections. Our study confirms the rapid spread of CP-E/K in Belgian hospitals and the urgent need for a well-structured and coordinated national surveillance plan in order to limit their dissemination.
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ORIGINAL ARTICLE
Increasing incidence of carbapenemase-producing Escherichia
coli and Klebsiella pneumoniae in Belgian hospitals
M. De Laveleye
1
&T. D. Huang
1
&P. Bogaerts
1
&C. Berhin
1
&C. Bauraing
1
&P. Sacré
1
&
A. Noel
1
&Y. Glupczynski
1
&on behalf of the multicenter study group
Received: 26 July 2016 /Accepted: 5 September 2016 /Published online: 17 September 2016
#Springer-Verlag Berlin Heidelberg 2016
Abstract Carbapenemase-producing Enterobacteriaceae are
increasingly reported worldwide. The aim of the study was
to determine the incidence and molecular epidemiology of
carbapenemase-producing (CP) Escherichia coli and
Klebsiella pneumoniae (CP-E/K) in Belgium. Eleven
hospital-based laboratories collected carbapenem non-
susceptible (CNS) isolates of E. coli and K. pneumoniae de-
tected in clinical specimens from January 2013 to December
2014. All CNS strains were tested for carbapenemase produc-
tion and typed by multilocus sequence typing (MLST) for a 6-
month period as part of the European Survey on
Carbapenemase-Producing Enterobacteriaceae in Europe
(EuSCAPE) structured survey. In addition, an equal number
of carbapenem-susceptible isolates collected were preserved
as a control group for risk factor analysis. The overall inci-
dence rate of CP-E/K isolates in hospitals increased from
0.124 in 2013 to 0.223 per 1000 admissions in 2014. From
November 2013 to April 2014, 30 CP K. pneumoniae [OXA-
48 (n= 16), KPC (n= 13), OXA-427 (n= 1)] and five CP
E. coli [OXA-48 (n= 3), NDM (n= 1), OXA-427 (n=1)]
isolates were detected in ten hospitals. The 16 OXA-48-
producing K. pneumoniae strains were distributed into eight
sequence types (STs), while the 13 KPC-producing
K. pneumoniae clustered into three STs dominated by
ST512 (n= 7) and ST101 (n= 5). Compared to controls, we
observed among CP-E/K carriers significantly higher propor-
tion of males, respiratory origins, previous hospitalization,
nosocomial setting, and a significantly lower proportion of
bloodstream infections. Our study confirms the rapid spread
of CP-E/K in Belgian hospitals and the urgent need for a well-
structured and coordinated national surveillance plan in order
to limit their dissemination.
Introduction
The spread of carbapenemase-producing Enterobacteriaceae
(CPE) is alarming and constitutes a major threat to public
health worldwide [1,2]. In most instances, carbapenemases
are associated with other β-lactamases and resistance to sev-
eral other classes of antimicrobials, rendering treatment par-
ticularly challenging. Moreover, carbapenemase-encoding
genes are easily transferable through plasmids and transpo-
sons, and have the propensity to spread amongst
Enterobacteriaceae [1].
In Belgium, the number of CPE isolates reported in hospi-
tals has increased dramatically since 2010 [3]. Over the recent
years, the epidemiological situation of CPE has worsened in
Europe, showing a doubling of the number of countries
reporting inter-regional spread or endemic situation for CPE
from 2013 to 2015 [4]. However, these data based on volun-
tary reporting or questionnaires assessment by national ex-
perts are not supported by objective epidemiological indica-
tors, which preclude precise comparisons to be made between
countries.
The present study, performed as part of the European
Survey on Carbapenemase-Producing Enterobacteriaceae in
Europe (EuSCAPE), aimed to determine the incidence and
the epidemiological characteristics of carbapenemase-
Members of the multicenter study group are listed in the
Acknowledgments section.
*T. D. Huang
te-din.huang@uclouvain.be
1
National Reference Laboratory of Antibiotic-Resistant
Gram-Negative Bacilli, CHU UCL Namur, Yvoir, Belgium
Eur J Clin Microbiol Infect Dis (2017) 36:139–146
DOI 10.1007/s10096-016-2782-x
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... The present study is focused on the molecular characterization of carbapenem-resistant hypermucoviscous K. pneumoniae. The incidence rate of these strains in our institution was 0.290 per 1000 admissions, higher than the rate registered in Belgium where the average incidence among 9 hospitals was 0.223 per 1000 admissions [28] and even greater than in Germany where it is significantly lower (0.047 per 1000 admissions) [29]. The average time of hospitalization prior to the acquisition of the infection was 30 days, denoting the high hospital stay; the Intensive Care Unit was the most common site of acquisition, in line with previous reports [26,30,31,32,33]. ...
... Antimicrobial susceptibility testing confirmed resistance to piperacillin/tazobactam, ciprofloxacin and meropenem in all isolates, higher than the results found in Belgian hospitals: 43.9%, 80.3% and 53% respectively. The resistance proportion for tigecycline and colistin was still lower with only 2 and 1 strain respectively [28]. ...
Virulence factors and clinical patterns of multiple-clone hypermucoviscous KPC-2 producing K. pneumoniae
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Carbapenemase-producing Klebsiella pneumoniae (CRKP) are increasingly reported worldwide being necessary the local epidemiological monitoring. Our aim was to characterize the hypermucoviscous CRKP isolates collected in our hospital during a 6 months period. Carriage of the carbapenemase genes (blaKPC, blaNDM, blaVIM and blaOXA-48), extended spectrum β-lactamases (blaSHV-2, blaCTX-M) and the virulence genes (magA, k2A, rmpA, wabG, uge, allS, entB, ycfM, kpn, wcaG, fimH, mrkD, iutA, iroN, hly and cnf-1) were determined by multiplex-PCR. Genetic relationship among the isolates was performed by PFGE and MLST. A total of 35 isolates were recovered, being the urinary and respiratory tract the most common infection sites (34.2%). The blaKPC-2 gene was present in all the isolates, coexisting with blaCTX-M-2 (45.7%), blaSHV-2 (28.6%), and blaCTX-M-2/blaSHV-2 (14.3%). The capsular serotype K2 corresponded with 68.6% of the isolates. Virulence factors frequency were variable [adhesins (97.1%), siderophores (94.3%) and phagocytosis resistance (wabG 48.5%, uge 80% and ycfM 57.1%)]. A total of 10 STs were identified although 40% of them clustered on ST25-CC65, and 17% to ST17. The incidence of KPC-2-producing K. pneumoniae reported by the hospital was 0.290 per 1000 admissions. In summary we described an epidemic scenario of multidrug resistant hypermucoviscous KPC-2 producing ST25 K. pneumoniae in our institution. Keywords: Epidemiology, Infectious disease, Microbiology, Carbapenemase, KPC, Klebsiella pneumoniae, Multi-clonal
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... In an EuSCAPE study, the incidence of CRKPN and CRECO increased from 0.124 per 1000 admissions in 2013 to 0.223 per 1000 admissions in 2014. 32 In our study, the incidence of CRE was increasing from 21.6% to 41.4% steadily, meanwhile, CRKPN exhibited substantial increase from 31.3% to 56.2%. Our retrospective data showed that the total proportion of CRE isolated from ICU, hematology department and infection department had amount to 78.0% (data not shown). ...
Bacterial Etiology and Antimicrobial Resistance Pattern of Pediatric Bloodstream Infections in Beijing, 2015–2019
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... Shortly after, in 2011, OXA-48 producing isolates from The Netherlands and Morocco were linked to the same sequence type/clone based on MLST and repetitive element sequence-based PCR [19]. ST395 isolates carrying OXA-48 plasmids have spread widely and were recovered either sporadically or from outbreaks in many countries in Europe (the Czech Republic, Denmark, France, Germany, Hungary, Ireland, Italy, Romania, Russia, Sweden, the UK), North Africa (Egypt, Algeria), Southeast Asia (Malaysia), and the Middle East (Israel, Kuwait) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Besides OXA-48, isolates of this genotype have been reported to carry different carbapenemases, such as KPC-2 in China [38], KPC-3 in Italy [39], NDM-1 in Russia [40,41], and NDM-1 and NDM-5 in Germany [8]. ...
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Article
Full-text available
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Background: Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage. Methods: We computationally analyzed a large collection of K. pneumoniae ST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features. Results: Clustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved different K. pneumoniae donors and affected, inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of “hybrid” resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype. Conclusions: To the best of our knowledge, this is the first study that investigated a large international collection of K. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage.
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... The PFGE and MLST analyses demonstrated the clonal diversity of our isolates that indicating the horizontal transfer of resistance genes between bacterial species through mobile elements such as plasmids that were in line with other reports [66,67]. K8, K10, and K12 pulsotypes were associated with ST147 that carried the bla OXA-1 and bla TEM genes. ...
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... La prévalence des entérobactéries multirésistantes aux antibiotiques est en augmentation depuis plusieurs années et ce phénomène est mondial [1][2][3][4] L'augmentation d' incidence des CPE est préoccupante, vu le nombre restreint d'antibiotiques actifs sur ces bactéries. En effet, la mortalité des infections sévères dues aux CPE (en particulier les bactériémies) est élevée, variant de 39 à 71 % 5-10 . ...
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... OXA-163 is rarely reported in Western countries but is most prevalent in South America and North Africa (Egypt) where it represents an important clinical issue [11,12]. Another rarely reported but interesting CHDL variant is OXA-427 which presents both ESBL and carbapenemase activities [13][14][15]. This enzyme presents a 77% amino acid identity with OXA-12 from Aeromonas sobria but only 29% with OXA-48. ...
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Class D β-lactamases exhibit very heterogeneous hydrolysis activity spectra against the various types of clinically useful β-lactams. Similarly, and according to the available data, their sensitivities to inactivation by avibactam can vary by a factor of more than 100. In this paper, we performed a detailed kinetic study of the interactions between two ceftazidime-hydrolyzing OXA enzymes and showed that they were significantly more susceptible to avibactam than several other class D enzymes that do not hydrolyze ceftazidime. From a clinical point of view, this result is rather interesting if one considers that avibactam is often administered in combination with ceftazidime.
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... Page 2 of 7 Li et al. Ann Clin Microbiol Antimicrob (2019) 18:34 are traditionally considered to be most effective agents against K. pneumoniae, is a major cause for concern [4,5]. Clonal expansion of drug-resistant strains has resulted in outbreaks in hospitals in several countries [6], leading to a high mortality in infected individuals. ...
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Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015
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In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015.
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The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to healthcare delivery, although its extent differs substantially from country to country. In February 2013, national experts from 39 European countries were invited to self-assess the current epidemiological situation of CPE in their country. Information about national management of CPE was also reported. The results highlight the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection control measures.
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This study presents the first characterization of carbapenem-non-susceptible Klebsiella pneumoniae isolates by means of a structured six-month survey performed in Romania as part of an Europe-wide investigation. Klebsiella pneumoniae clinical isolates from different anatomical sites were tested for antibiotic susceptibility by phenotypic methods and confirmed by PCR for the presence of four carbapenemase genes. Genome macrorestriction fingerprinting with XbaI was used to analyze the relatedness of carbapenemase-producing Klebsiella pneumoniae isolates collected from eight hospitals. Among 75 non-susceptible isolates, 65 were carbapenemase producers. The most frequently identified genotype was OXA-48 (n = 51 isolates), eight isolates were positive for blaNDM-1 gene, four had the blaKPC-2 gene, whereas two were positive for blaVIM-1. The analysis of PFGE profiles of OXA-48 and NDM-1 producing K. pneumoniae suggests inter-hospitals and regional transmission of epidemic clones. This study presents the first description of K. pneumoniae strains harbouring blaKPC-2 and blaVIM-1 genes in Romania. The results of this study highlight the urgent need for the strengthening of hospital infection control measures in Romania in order to curb the further spread of the antibiotic resistance.
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Molecular epidemiology of carbapenem resistant Enterobacteriaceae in Valle d’Aosta region, Italy, shows the emergence of KPC-2 producing Klebsiella pneumoniae clonal complex 101 (ST101 and ST1789)
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  • Nov 2015
  • BMC MICROBIOL
Background The spread of carbapenem resistant Enterobacteriaceae (CRE) is an emerging clinical problem, of great relevance in Europe and worldwide. The aim of this study was the molecular epidemiology of CRE isolates in Valle d’Aosta region, Italy, and the mechanism of carbapenem resistance. Results Sixty consecutive CRE samples were isolated from 52 hospital inpatients and/or outpatients from November 2013 to August 2014. Genotyping of microbial isolates was done by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST), carbapenemases were identified by PCR and sequencing. Carbapenem resistance gene transfer was performed by filter mating, plasmids from parental and transconjugant strains were assigned to incompatibility groups by PCR-based replicon typing. Molecular characterization of CRE isolates assigned 25 Klebsiella pneumoniae isolates to PFGE types A1-A5 and sequencing type (ST) 101, 17 K. pneumoniae isolates to PFGE type A and ST1789 (a single locus variant of ST101), 7 K. pneumoniae isolates to PFGE types B or C and ST512, 2 K. pneumoniae isolates to PFGE type D and ST405, and 5 Escherichia coli isolates to PFGE type a and ST131. All K. pneumoniae ST101 and ST1789 isolates were extended-spectrum beta-lactamase (ESBL) producers and carried blaCTX-M-1 group gene; 4 K. pneumoniae ST101 isolates were resistant to colistin. Molecular analysis of beta-lactamase genes identified blaKPC-2 and blaCTX-M-group 1 into conjugative plasmid/s assigned to IncFII incompatibility group in ST101 and ST1789 K. pneumoniae isolates, blaKPC-3 into conjugative plasmid/s assigned to IncF incompatibility group in ST512 and ST405 K. pneumoniae isolates, blaVIM-1 into conjugative plasmid/s assigned to IncN incompatibility group in ST131 E. coli isolates. Conclusions The spread of CRE in Valle d’Aosta region was caused by the selection of KPC-2 producing K. pneumoniae ST101 and ST1789 epidemic clones belonging to clonal complex 101, KPC-3 producing K. pneumoniae epidemic clones assigned to ST512 and ST405, and VIM-1 producing E.coli ST131 epidemic clone. Carbapenem resistance, along with blaKPC-2, blaKPC-3 and blaVIM-1 carbapenemase genes, was transferred by conjugative plasmids assigned to IncFII, IncF, and IncN incompatibility groups, respectively, in filter mating experiments. The emergence of colistin resistance was observed in KPC-2 producing K. pneumoniae ST101 isolates. Electronic supplementary material The online version of this article (doi:10.1186/s12866-015-0597-z) contains supplementary material, which is available to authorized users.
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One of the most important threats of current medicine is the spread of multiresistant Gram-negative bacteria. We report here data from a six-month prevalence study on carbapenemase-producing K. pneumoniae and E. coli performed in Czech hospitals participating on European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE). Ten hospitals covering all regions of the Czech Republic were selected. During the study period (1st November 2013 to 30th April 2014), first ten carbapenem non-susceptible isolates of K. pneumoniae or E. coli isolated from non-surveillance specimens (i.e., blood, lower respiratory tract secretions, urine, puncture fluids, and wound secretions) of single successive patients were collected. Successive carbapenem-susceptible isolates of the same species were also preserved as controls. Susceptibility to 15 antibiotics was determined using EUCAST recommendations. Carbapenemase activity was detected by MALDI-TOF MS meropenem hydrolysis assay. Positive isolates were subjected for molecular typing (multi-locus sequence typing, identification of carbapenemase gene). During the study period, thirty non-susceptible isolates (K. pneumoniae n = 28, E. coli n = 2) were identified in 5 hospitals. Only two of them were confirmed to be carbapenemase producers. A NDM-1-producing K. pneumoniae ST11 was recovered from a patient, transferred from Ukraine, being injured during a Maidan revolution. The second isolate, an OXA-48-producing K. pneumoniae, belonging to ST101, was recovered from a patient admitted to a hospital for an ischemic stroke. This study again confirmed that the Czech Republic still belongs to the countries with low prevalence of carbapenemase-producing Enterobacteriaceae (CPE). Cases of CPE are usually restricted to an import from high-prevalence countries or countries with unknown epidemiological situation.
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Infection due to travel-related carbapenemase-Producing Enterobacteriaceae, a largely underestimated phenomenon in Belgium
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Full-text available
  • Mar 2015
Carbapenemase-producing Enterobacteriaceae (CPE) are emerging worldwide, representing a major threat for public health. Early CPE detection is crucial in order to prevent infections and the development of reservoirs/outbreaks in hospitals. In 2008, most of the CPE strains reported in Belgium were imported from patients repatriated from abroad. Actually, this is no longer the case. A surveillance was set up in Belgian hospitals (2012) in order to explore the epidemiology and determinants of CPE, including the link with international travel/hospitalization. The present article describes travel-related CPE reported in Belgium. Different other potential sources for importation of CPE are discussed. Only 12% of all CPE cases reported in Belgium (2012-2013) were travel related (with/without hospitalization). This is undoubtedly an underestimation (missing travel data: 36%), considering the increasing tourism, the immigration from endemic countries, the growing number of foreign patients using scheduled medical care in Belgium, and the medical repatriations from foreign hospitals. The free movement of persons and services (European Union) contributes to an increase in foreign healthcare workers (HCW) in Belgian hospitals. Residents from nursing homes located at the country borders can be another potential source of dissemination of CPE between countries. Moreover, the high population density in Belgium can increase the risk for CPE-dissemination. Urban areas in Belgium may cumulate these potential risk factors for import/dissemination of CPE. Ideally, travel history data should be obtained from hospital hygiene teams, not from the microbiological laboratory. Patients who received medical care abroad (whatever the country) should be screened for CPE at admission.
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Prospective Multicenter Study of Carbapenemase-Producing Enterobacteriaceae from 83 Hospitals in Spain Reveals High In Vitro Susceptibility to Colistin and Meropenem
Article
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The aim of this study was to determine the impact of the carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2013 by describing their prevalence, dissemination and geographic distribution of CPE clones, their population structure and antibiotic susceptibility. From February 2013 to May 2013, 83 hospitals (about 40,000 hospital beds) prospectively collected non-duplicate Enterobacteriaceae using the screening cut-off recommended by EUCAST. Carbapenemase characterisation was performed by phenotypic methods and confirmed by PCR and sequencing. MLST types were determined for Klebsiella pneumoniae and Escherichia coli. A total of 702 Enterobacteriaceae isolates met the inclusion criteria; 379 (54%) were CPE. OXA-48 (71.5%) and VIM-1 (25.3%) were the most frequent carbapenemases, and K. pneumoniae (74.4%), Enterobacter cloacae (10.3%), and E. coli (8.4%) were the species most affected. Susceptibility to colistin, amikacin and meropenem was 95.5%, 81.3%, and 74.7%, respectively. The most prevalent STs were ST11 and ST405 in K. pneumoniae, and ST131 in E. coli. Forty-five (54.1%) of the hospitals had at least one CPE case. In K. pneumoniae, ST11/OXA-48, ST15/OXA-48, ST405/OXA-48, and ST11/VIM-1 were detected in two or more Spanish provinces. ST11 carried four carbapenemases (VIM-1, OXA-48, KPC-2, and OXA-245), but ST405 carried OXA-48 only. A wide interregional spread of CPE in Spain was observed mainly due to a few successful clones of OXA-48-producing K. pneumoniae (e.g. ST11 and ST405). Dissemination of OXA-48-producing E. coli is a new finding of public health concern. According to in vitro susceptibilities, most of the CPE (94.5%) had three or more options of antibiotic treatment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: A rapidly evolving problem in Italy, November 2013 to April 2014
Article
Full-text available
  • Oct 2014
  • Euro Surveill
Consecutive non-replicate clinical isolates (n=191) of carbapenem non-susceptible Enterobacteriaceae were collected from 21 hospital laboratories across Italy from November 2013 to April 2014 as part of the European Survey on Carbapenemase-producing Enterobacteriaceae (EuSCAPE) project. Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) represented 178 (93%) isolates with 76 (43%) respectively resistant to colistin, a key drug for treating carbapenamase-producing Enterobacteriaceae. KPC-KP colistin-resistant isolates were detected in all participating laboratories. This underscores a concerning evolution of colistin resistance in a setting of high KPC-KP endemicity.
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Multicentre investigation of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in German hospitals
Article
  • May 2016
Aim of this study was to determine the incidence and molecular epidemiology of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Germany. E. coli and K. pneumoniae isolates from clinical samples which were non-susceptible to carbapenems were collected in laboratories serving 20 hospitals throughout Germany from November 2013 to April 2014. The isolates were tested for the presence of carbapenemases by PCR and phenotypic methods and typed by multilocus sequence typing. Risk factors including a previous hospitalization abroad were analysed. Carbapenemases were detected in 24 isolates from 22 patients out of 464,514 admissions. Carbapenemases included OXA‐48 (n = 14), KPC‐2 (n = 8) and NDM‐1 (n = 2). Except for two K. pneumoniae isolates with ST101, all OXA‐48 producing strains belonged to different clones. In contrast, half of KPC‐2 producing K. pneumoniae were of ST258 and both NDM‐1 producing strains were of ST11. Compared to carbapenem-susceptible controls, patients with carbapenemase-producing strains differed by a significantly higher proportion of males, a higher proportion of isolates from wound samples and a more frequent previous stay abroad in univariate analysis. This multicentre study demonstrated an incidence of carbapenemase-producing E. coli and K. pneumoniae from clinical samples in Germany of 0.047 cases per 1000 admissions. OXA‐48 was more frequent than KPC‐2 and NDM‐1 and showed a multiclonal background.
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Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study
Article
  • Nov 2015
  • LANCET INFECT DIS
Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10(-1) to 10(-3) cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China.
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