(2011) - Multiresistant Gram-Negative Bacteria - The Role of High-Risk Clones in The Dissemination of Antibiotic Resistance. Woodford Et. Al

REVIEW ARTICLE
Multiresistant Gram-negative bacteria: the role of high-risk clones

in the dissemination of antibiotic resistance
Neil Woodford, Jane F. Turton & David M. Livermore
Microbiology Services - Colindale, Health Protection Agency, London, UK
Correspondence: Neil Woodford, Abstract

Microbiology Services - Colindale, Health
Protection Agency, ARMRL, 61 Colindale
Multilocus sequence typing reveals that many bacterial species have a clonal
Avenue, London NW9 5EQ, UK. Tel.: 144 20 structure and that some clones are widespread. This underlying phylogeny was not
8327 7255; revealed by pulsed-field gel electrophoresis, a method better suited to short-term
fax: 144 20 8327 6264; outbreak investigation. Some global clones are multiresistant and it is easy to
e-mail: neil.woodford@hpa.org.uk assume that these have disseminated from single foci. Such conclusions need
caution, however, unless there is a clear epidemiological trail, as with KPC
Received 24 September 2010; revised 4 January carbapenemase-positive Klebsiella pneumoniae ST258 from Greece to northwest
2011; accepted 19 January 2011.
Europe. Elsewhere, established clones may have repeatedly and independently
Final version published online 1 March 2011.
acquired resistance. Thus, the global ST131 Escherichia coli clone most often has
DOI:10.1111/j.1574-6976.2011.00268.x
CTX-M-15 extended-spectrum b-lactamase (ESBL), but also occurs without
ESBLs and as a host of many other ESBL types. We explore this interaction of
Editor: Teresa Coque clone and resistance for E. coli, K. pneumoniae, Acinetobacter baumannii – a species
where three global lineages dominate – and Pseudomonas aeruginosa, which shows
Keywords clonal diversity, but includes the relatively ‘tight’ serotype O12/Burst Group 4
ESBL; carbapenemase; Enterobacteriaceae; cluster that has proved adept at acquiring resistances – from PSE-1 to VIM-1 b-
Acinetobacter; Pseudomonas. lactamases – for over 20 years. In summary, ‘high-risk clones’ play a major role in
the spread of resistance, with the risk lying in their tenacity – deriving from poorly
MICROBIOLOGY REVIEWS
understood survival traits – and a flexible ability to accumulate and switch

resistance, rather than to constant resistance batteries.
no-cephalosporins in addition to other drug classes, but will

Introduction also mention clones associated with other or, in some cases,
Multiresistance is considered to be a key indicator of no problematic resistances. We focus on four species as
problematic bacterial strains because (1) it undermines exemplars, Escherichia coli, Klebsiella pneumoniae, Acinetobac-
empirical treatment regimens, thereby delaying the admin- ter baumannii and Pseudomonas aeruginosa, although wide-
istration of appropriate antibiotic therapy, and (2) it reduces spread clones of other genera, including, but not limited to
the options of treatments that are appropriate. Both factors Enterobacter, Proteus, Citrobacter and Serratia, have been
contribute to increased patient mortality, and limiting the reported and may be endemic in certain areas.
spread of multiresistant strains is considered to be an infection Multiresistant bacteria serve as hosts for the multiple
control priority. Despite this, the term ‘multi-resistance’ genetic elements (genes, integrons, transposons and plasmids)
remains poorly defined and there is conflicting usage in the that confer their antibiotic resistance phenotypes. These are
literature (Schwarz et al., 2010). There are presently moves to discussed elsewhere in this issue. A ‘successful’ bacterial strain
define ‘multiresistance’ as resistance to three or more drug is an extremely effective vehicle for the dissemination of these
classes and ‘extreme’ resistance as susceptibility to no more elements for at least two reasons: firstly, all of the hosted
than two classes, but this remains contentious, not least resistance elements are transmitted vertically (i.e. from mother
because the latter definition potentially varies between labora- to daughter cells) by virtue of the strain’s spread and its
tories that test different panels of agents. In this review of increasing prevalence; secondly, a successful strain has multi-
important Gram-negative clones, we will focus on bacteria ple opportunities to act as a donor and to transfer its resistance
that have acquired resistance to carbapenems and/or oxyimi- elements horizontally to other strains, species or genera.

c 2011 Federation of European Microbiological Societies FEMS Microbiol Rev 35 (2011) 736–755
Published by Blackwell Publishing Ltd. All rights reserved
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on 12 February 2018
Multiresistant Gram-negative bacterial clones 737
Multiresistance prompts investigation, particularly when define types, is excellent for evolutionary studies, and for
associated with an outbreak in a healthcare or a community readily comparing isolates, but may lack the discrimination
setting, and this commonly leads to molecular epidemiolo- required for outbreak analysis (van Belkum et al., 2007;
gical analysis of the causative bacteria and their resistance Diancourt et al., 2010). It has led to the definition of major
genes. The recognition of a prevalent and successful multi- sequence types (STs) and clonal complexes (CCs) of signifi-
resistant strain or clone should prompt further questions, cance in a number of species, and the growing recognition of
not least about: (1) whether it is genuinely a newly emerged successful, international clones, such as K. pneumoniae ST258,
entity, or a previously minor strain, with resistance a key increasingly associated with KPC carbapenemase, and the
driver in its rise to success, or (2) whether it was a pre- community-acquired K. pneumoniae CC23, associated with
existing successful, but antibiotic-susceptible strain receiv- invasive disease (Baraniak et al., 2009; Brisse et al., 2009;
ing increased attention owing to the recent acquisition of Kitchel et al., 2009a; Samuelsen et al., 2009b). The relation-
multiple resistance by gene transfer. These possibilities are ships between the various STs and CCs can conveniently be
often difficult to distinguish because fully antibiotic-suscep- depicted by e-BURST diagrams (Feil et al., 2004).
tible bacteria attract less attention, which may confound PFGE, following restriction of genomic DNA with an
attempts to consider resistant strains in the context of the appropriate rare-cutting enzyme, provides excellent discri-
population biology of a particular species. Evidence is mination and has been used widely for typing of a range of
emerging to indicate that particular host clones acquire bacterial species (Coenye et al., 2002; Lau et al., 2008a; Long
similar resistance genes on multiple occasions, and that et al., 2010), but is not as ‘portable’ as are methods such as
evolution fine-tunes these associations to maintain or MLST and MVLA, which describe isolates numerically. PCR
increase bacterial fitness (Deschamps et al., 2009). fingerprinting methods are popular typing methods, too,
but, with the exception of AFLP, are often considered not
very reproducible between laboratories. An automated rep-
Defining ‘strains’ and ‘clones’ PCR method, however, is increasingly being used, and may
The terms ‘strain’ and ‘clone’ are used widely, but their provide discrimination similar to that of PFGE (Diaz et al.,
meaning can be open to interpretation. As far as possible, we 2010; Ligozzi et al., 2010; Ratkai et al., 2010). MVLA, a PCR-
will follow the recommendations of recently published guide- based method that involves determining the number of repeat
lines (van Belkum et al., 2007). Thus, ‘strain’ should not be units at multiple loci with short sequence repeats, is rapidly
confused with ‘isolate’ because isolates that are indistinguish- gaining popularity for epidemiological investigations, and is
able by typing can be considered as descendants of the same also portable (Lindstedt, 2005; van Belkum, 2007; Vu-Thien
strain, whereas ‘strains’ should be distinguishable from one et al., 2007; Kendall et al., 2010; Teh et al., 2010); its dis-
another by typing methods. There is no precise definition of criminatory power varies with the loci chosen, providing the
how closely related isolates need to be in order to be potential to tailor the typing at an appropriate resolution.
considered to represent the same strain, and the decision The ability of this method to provide higher resolution than
reached may depend on the typing method used. PFGE has been exploited in a number of studies (Turton et al.,
Determining whether to use the term ‘strain’ or ‘clone’ is 2009; Li et al., 2010).
even more difficult, especially given that the logical usage of The typing method used must be appropriate to the
the word ‘clone’ is to describe isolates that are directly question asked. To track individual transmissions, a highly
descended from an original; the word is commonly used as discriminatory method is required and many typing techni-
an alternative to ‘strain’. Nevertheless, it was proposed that ques fall short of this. On the whole, SNP and whole-
‘clone’ be used ‘to describe isolates that, although they may genome approaches are more suitable for this (Zhang et al.,
have been cultured independently from different sources in 2006; Niemann et al., 2009; Lewis et al., 2010). On the other
different locations and perhaps at different times, still have hand, such techniques may overemphasize minor differ-
so many identical phenotypic and genotypic similarities that ences and fail to recognize that isolates are largely similar.
the most likely explanation is a common origin’ (Orskov & Hence, PFGE subdivided isolates of A. baumannii so well
Orskov, 1983). This wider explanation commonly applies to that the fact that most isolates belonged to European clones
multiresistant bacteria found in multiple locations. I and II was not recognized for some time (Turton et al.,
Among the most common methods currently used for 2007; Higgins et al., 2009, 2010a). MLST- and sequence-
genotyping of bacteria are multilocus sequence typing based typing have been instrumental in identifying major
(MLST), pulsed-field gel electrophoresis (PFGE), amplified international clones, with many of those included here
fragment length polymorphism (AFLP) analysis, other having been described by this method, but each level of
PCR fingerprinting methods and multiple-locus variable discrimination is important; in the above example, the
tandem repeat number analysis (MVLA). MLST, which uses finding of distinct PFGE types of the same clonal lineage of
sequence variation in a number of housekeeping genes to A. baumannii, indicating independent selection from a
FEMS Microbiol Rev 35 (2011) 736–755

c2011 Federation of European Microbiological Societies

on 12 February 2018
738 N. Woodford et al.
ST405
ST131
ST10
Fig. 1. ‘Population Snapshot’ determined by

eBURST analysis (http://eburst.mlst.net) showing
the clusters of linked STs and unlinked STs in the
Escherichia coli MLST database (‘Achtman’
scheme; 1899 STs; http://mlst.ucc.ie/mlst/dbs/Eco
li; last accessed 30 December 2010). ST labels
have been removed. Major CCs and STs referred
ST23 ST69 to in the text are indicated.
common ancestor, rather than simple spread, is an impor- (Fig. 1). Representatives were originally reported in Canada,
tant observation that is critical to an understanding of France, Lebanon, Portugal, South Korea, Spain and Switzer-
the epidemiology. land, but this clone has subsequently been reported far more
widely (Johnson et al., 2010; Peirano & Pitout, 2010; Platell
et al., 2010; Rogers et al., 2011). ST131 is a ‘virulent’
Extraintestinal E. coli phylogroup B2, uropathogenic E. coli lineage, which can be
Escherichia coli is the most common agent of urinary tract recognized by allele-specific PCR of the pabB gene (Clermont
infections and the leading Gram-negative cause of bacterae- et al., 2009; Dhanji et al., 2010), and may be subdivided into
mia. Since the mid 1990s or early 2000s, according to the multiple variants by PFGE (Coque et al., 2008; Lau et al.,
country, there has been a worldwide increase in the prevalence 2008a; Nicolas-Chanoine et al., 2008). These variants have
of isolates that are resistant to oxyimino-cephalosporins (e.g. diverse complements of virulence factors, albeit with key
http://www.earss.rivm.nl) and produce extended-spectrum b- common components (Karisik et al., 2008; Nicolas-Chanoine
lactamase (ESBLs), particularly CTX-M type enzymes (Can- et al., 2008; Bert et al., 2010; Johnson et al., 2010). Perhaps
ton & Coque, 2006; Livermore et al., 2007). Considered reflecting this diversity, it would appear that not all ST131
globally, CTX-M-15 and CTX-M-14 are the most prevalent variants are created equal, with some better able to spread
members of this family of 4 110 ESBL variants. As a than others. In the United Kingdom, the most prevalent
consequence of this increase, research interest in the biology variant, designated strain A, has been isolated in 4 50
of multiresistant, extraintestinal pathogenic E. coli strains has microbiology laboratories, serving one or more hospitals each,
increased dramatically, and has included studies to elucidate whereas a second variant, strain D, has been restricted to just
the epidemiology of the current ‘CTX-M ESBL pandemic’. one hospital (Woodford et al., 2004b). The biological factors
There are several MLST schemes for E. coli, but those in that contribute to success and varied epidemiological features
widest use are the ‘Achtman’ (Wirth et al., 2006) (http://mlst. of some variants/strains within a clone remain undefined.
ucc.ie/mlst/dbs/Ecoli) and ‘Pasteur’ (Jaureguy et al., 2008) In the United Kingdom, the five initially most prevalent
(http://www.pasteur.fr/recherche/genopole/PF8/mlst/EColi. strains of E. coli with CTX-M enzymes were defined as A–E
html) schemes. Inconveniently, there has been only a limited by PFGE (Woodford et al., 2004b), and the fact that they all
attempt to match the ST designations assigned by these belonged to ST131 was not recognized for several years
schemes (Jaureguy et al., 2008) (http://www.biomedcentral. (Lau et al., 2008a). This clearly illustrates the benefits of
com/content/supplementary/1471-2164-9-560-S4.xls). The investigating emergence events at multiple levels, using both
application of MLST to isolates producing CTX-M-15 ESBL a population-focused approach, such as MLST, and a strain
led to the recognition of an internationally disseminated typing method such as PFGE.
clone, B2,O25:H4-ST131 (with its ST defined according to Most ST131 isolates in the United Kingdom produce CTX-
the ‘Achtman’ scheme) (Nicolas-Chanoine et al., 2008) M-15 ESBL (Woodford et al., 2004b; Lau et al., 2008a, b), but


on 12 February 2018
some have the CTX-M-3 enzyme (Rooney et al., 2009), while enzymes (Guillouzouic et al., 2009; Cremet et al., 2010);
others have additionally acquired a CMY-type AmpC enzyme STs 155 and 359 (both phylogroup B1) have been isolated
(Woodford et al., 2007). This illustrates the fact that members from Spanish, Portuguese and Brazilian outpatients (Val-
of single widespread clones may harbour different resistance verde et al., 2009; Oteo et al., 2010b).
genes and so may display different susceptibility profiles. If Several multiresistant E. coli clones (e.g. ST131, ST69,
clones are circulating widely, they are prone to acquire whatever ST23) have been isolated from non-human sources, includ-
resistance plasmids are locally prevalent and ST131 variants ing farm and companion animals, river water and foods,
may harbour diverse plasmids (Woodford et al., 2009). In indicating the wide distribution and the potential complex-
Japanese hospitals, clone O25:H4-ST131 was one of two ity of transmission routes (Johnson et al., 2009; Ewers et al.,
dominant clones among ESBL-producing E. coli isolates, but 2010; Guenther et al., 2010; Ozawa et al., 2010; Vincent et al.,
variously produced CTX-M-14, CTX-M-2 or -35 ESBLs rather 2010; Dhanji et al., 2011; Rogers et al., 2011).
than CTX-M-15. The other dominant clone in this study was Although E. coli has emerged as the major producer of
O86:H18-ST38 with CTX-M-9 or CTX-M-14 enzymes (Suzuki CTX-M-type ESBLs, including in the community setting, it
et al., 2009). ESBL-negative ST131 isolates have also been found is less often associated with carbapenemases than K. pneu-
for example in stools of 7% of healthy residents in Paris moniae. NDM-1 carbapenemase was detected recently in
(Leflon-Guibout et al., 2008). Recently, E. coli ST131 isolates France in an isolate of E. coli belonging to the ST131 lineage
in Madrid were reported to produce the inhibitor-resistant (Poirel et al., 2010a). If carbapenemases become widely
enzymes TEM-30, -33 and -37, all encoded by IncFII plasmids established in this or other successful clones, it would create
(Martin et al., 2010). The current geographic distribution of a significant public health concern, given the burden of
ST131 and its resistance traits have been reviewed recently disease caused by E. coli.
(Rogers et al., 2011). ST131 is the predicted founder of a clonal
cluster that comprises 13 single locus variants (SLVs) and three
double locus variants (DLVs) (Fig. 1).
Klebsiella pneumoniae
Escherichia coli lineages of ‘virulent’ phylogroup D that An MLST scheme for K. pneumoniae was established in 2005.
have been associated with multiresistance include ST69 The original analysis identified 40 STs among 67 isolates
(‘clonal group A’; CgA), ST405 and O15:K52:H1 (Tartof (Diancourt et al., 2005), and found evidence for only two
et al., 2005; Cagnacci et al., 2008; Coque et al., 2008; Platell CCs, which comprised STs 14 and 15 and STs 16–22,
et al., 2010). ‘Clonal group A’ accounts for up to 50% of respectively. Nineteen ceftazidime-resistant isolates producing
cotrimoxazole-resistant isolates from urinary tract infec- ESBLs were divided between 11 STs, and the authors con-
tions in some United States locales (Manges et al., 2001); cluded that ‘resistance is not restricted to a few genetic back-
many of its resistance genes are located in a 23-kb ‘genomic grounds and that it is a problem of multiple emergence rather
resistance module’ within a 105-kb chromosomal island that than one of interhospital spread of a few clones.’ (Diancourt
is inserted into a leuX tRNA integration hotspot (Lescat et al., 2005). The database (http://www.pasteur.fr/recherche/
et al., 2009). ST405 is increasingly reported worldwide, genopole/PF8/mlst/Kpneumoniae.html) now includes 542
associated or not with production of CTX-M-15 ESBL STs and many workers have documented unequivocally the
(Jones et al., 2008; Fam et al., 2010; Mihaila et al., 2010; international spread of certain STs, particularly those asso-
Smet et al., 2010). The phylogroup D clones O1:HNM-D- ciated with KPC carbapenemases.
ST59, O15:H1-D-ST393/ST1394 and O20:H34/HNM-D- A blaKPC gene is a readily identifiable marker and has
ST354 have been reported among producers of CTX-M-14 sufficient clinical importance to justify a detailed investiga-
ESBL in Spain (Mora et al., 2011). The CMY-2 enzyme was tion, meaning that we know the epidemiology of the host
found in eight phylogroup D STs in Spain, mainly STs 57, strains in considerable detail. Producers of KPC enzymes,
115, 354, 393 and 420 (Oteo et al., 2010a). particularly the dominant KPC-2 and KPC-3 variants, have
Both ST131 (Clermont et al., 2008) and ST405 (Mihaila become endemic in the United States (Yigit et al., 2001;
et al., 2010) are highly virulent, as judged by PCR screening Smith Moland et al., 2003; Bradford et al., 2004; Woodford
for virulence genes and using both in vitro and animal et al., 2004a; Bratu et al., 2005c; Endimiani et al., 2008,
models. Indeed, transmission among family members has 2009a, b; Kitchel et al., 2009a), Greece (Cuzon et al., 2008b;
been documented for each of these clones (Ender et al., Tsakris et al., 2008b; Giakoupi et al., 2009; Pournaras et al.,
2009; Mihaila et al., 2010). 2009) and Israel (Leavitt et al., 2007, 2010; Navon-Venezia
In addition to lineages of phylogroups B2 and D, some et al., 2009), and with increasing numbers of reports with a
E. coli clones belonging to groups A and B1 are increasingly wide geographic scatter, including from China (Wei et al.,
reported and associated with resistance: STs 10 and 23 (both 2007; Zhang et al., 2007; Mendes et al., 2008), South
phylogroup A) have been associated with ESBLs (Oteo et al., America (Villegas et al., 2006; Monteiro et al., 2009; Pavez
2009; Valverde et al., 2009) and hyperexpressed AmpC et al., 2009; Peirano et al., 2009) and many countries in


on 12 February 2018
ST258
ST11
ST14
Fig. 2. ‘Population Snapshot’ determined by
eBURST analysis (http://eburst.mlst.net) showing
the clusters of linked STs and unlinked STs in the
entire Klebsiella pneumoniae MLST database (542
‘CC292’
STs; http://www.pasteur.fr/recherche/genopole/
PF8/mlst/; last accessed 30 December 2010). ST
labels have been removed. There is a large CC
comprising 96 STs (‘CC292’; green box) and with
ST292 as the predicted founder. This CC includes
many internationally prevalent and multiresistant
STs, including STs 11, 14 and 258.
Europe (Naas et al., 2005; Woodford et al., 2008; Samuelsen recovered from patients who had been repatriated from
et al., 2009b; Curiao et al., 2010; Kassis-Chikhani et al., 2010; Greece and Israel where KPC-positive ST258 isolates are
Mammina et al., 2010; Toth et al., 2010). The European well known to be prevalent. An isolate belonging to ST11,
isolates are often, but by no means always associated with an i.e. the same CC as ST258 (Fig. 2), and also producing a KPC
original patient transfer from an endemic area; similar enzyme was imported more recently to the United Kingdom
transfer has also been reported to Canada (Goldfarb et al., from Curaçao in the Caribbean (N. Virgincar et al., unpub-
2009). Although K. pneumoniae is the major host species, lished data). This latter ST also seems to be widespread
blaKPC genes are associated with transposons and transmis- independent of KPC carbapenemase; it was the most prevalent
sible plasmids and have been reported in other Enterobacter- ST among 77 ESBL-producing isolates isolated from urinary
iaceae (Miriagou et al., 2003b; Hossain et al., 2004; Bratu tract infections (57%) and blood (70%) in a multicentre survey
et al., 2005a, 2007; Navon-Venezia et al., 2006; Zhang et al., of 10 university hospitals in South Korea (Ko et al., 2010).
2007, 2008; Cai et al., 2008; Petrella et al., 2008; Tibbetts These ST11 isolates from Korea had at least eight different ESBL
et al., 2008; Bennett et al., 2009; Goren et al., 2010), in genotypes (none had KPC enzymes), implying multiple acqui-
Pseudomonas spp. (Villegas et al., 2007; Akpaka et al., 2009; sition events and the presence of multiple circulating variants of
Bennett et al., 2009; Wolter et al., 2009b; Poirel et al., 2010b) the clone. The authors emphasized that ‘specific PFGE patterns
and in Acinetobacter spp. (Robledo et al., 2010). were not related with a specific hospital or a specific ESBL gene.’
The globally distributed ST of K. pneumoniae associated ST11 is also associated with the spread of CTX-M-15 ESBL
with KPC enzyme production is ST258 (Kitchel et al., 2009a; throughout Hungary (Damjanova et al., 2008).
Navon-Venezia et al., 2009). This is part of a CC, founded on The first isolate with a KPC enzyme in Hungary was also
ST292, that includes 96 STs, (Fig. 2). Isolates belonging to this from a patient repatriated from a Greek hospital (Toth et al.,
complex appear to be widespread independent of KPC 2010). This, and subsequent isolates, belonged to ST258 and
carbapenemase. For example, ST258 has also been identified harboured blaKPC-2, blaSHV-12, blaTEM-1 and blaSHV-11. The
as a host of CTX-M-14 ESBL in South Korea (Ko et al., 2010). authors also highlighted a wider association between ST11
Despite this, the rapid, multifocal emergence of clonally related isolates and SHV-11 ESBL in Hungary. They proposed that
isolates with KPC carbapenemase is highly suggestive of direct, CC258 and 340 belong to a hyperepidemic CC – including
human-mediated international spread, rather than the re- ST11, ST258, ST265, ST270, ST277, ST340, ST379, ST407,
peated acquisition of similar plasmids by a prevalent clone. ST418 and ST437 – that occurs worldwide (Toth et al., 2010)
The first isolate with KPC carbapenemase in France was (http://www.pasteur.fr/recherche/genopole/PF8/mlst/
cultured from a patient who had been treated 2 months Kpneumoniae.html). This view is supported by MLST data,
previously in a New York City hospital (Naas et al., 2005), although the CC encompasses far more STs than originally
although its ST was not recorded. The first producers in envisaged (currently 96; Fig. 2).
Norway, Sweden (Samuelsen et al., 2009b) and the United By contrast, the first KPC-positive isolates reported in
Kingdom (Woodford et al., 2008) included ST258 isolates Madrid were from eight patients and belonged mainly to a


on 12 February 2018
novel type, ST384, with a single isolate of ST388. Isolates elsewhere, although anecdotal reports exist. Strains that
belonging to this latter type had already persisted in the produce multiple noncarbapenemase b-lactamases are well
hospital for over 10 years as hosts of CTX-M-10 ESBL and known (Moland et al., 2007).
had probably acquired blaKPC through horizontal plasmid Klebsiella pneumoniae with a distinct class of carbapene-
spread (Curiao et al., 2010). Despite the international mase, the class D enzyme OXA-48, have caused hospital
dominance of ST258, this study provides a clear warning of outbreaks in Istanbul, Turkey (Carrer et al., 2008), and there
the potential for the spread of plasmids encoding KPC is evidence to suggest that producers are widely scattered in
carbapenemases (and, indeed, any resistance) to other that country (Gulmez et al., 2008; Carrer et al., 2010),
strains, including those that may be locally prevalent and although there has been no reported national surveillance.
more usually associated with distinct antibiograms. Mole- Elsewhere, reports of OXA-48 producers are sporadic, from
cular epidemiological studies of bacteria with a newly Belgium, Egypt, France, Lebanon, Tunisia and the United
emerged resistance pattern should include local strains as Kingdom (Cuzon et al., 2008a, 2009, 2010; Zhang et al., 2009;
comparators wherever possible to put the emergence into Carrer et al., 2010), with spread of the gene to other
the proper local context. Enterobacteriaceae (Gulmez et al., 2008; Castanheira et al.,
Other K. pneumoniae STs reported as hosts of KPC 2009; Goren et al., 2009; Carrer et al., 2010). A hospital
enzymes include, in the United States, STs 14, 21, 37, 45, outbreak, centred on a renal unit, of K. pneumoniae with the
101, 228, 234, 257 and 259, with most found in at least two OXA-48 enzyme has been described in London, UK; although
states (Kitchel et al., 2009a, b), and, in Israel, STs 277, 327, there was a dominant ‘outbreak’ strain, several minor strains
340 (all members of ‘CC292’) and 376 (Leavitt et al., 2010). were defined by PFGE, suggesting the spread of an OXA-48-
In addition to strains with KPC carbapenemases, K. encoding plasmid (Thomas et al., 2009), and all were distinct
pneumoniae isolates that produce VIM-type metallo-b-lacta- by PFGE from ‘clones A and B’, which have caused outbreaks
mases (MBLs) are also endemic in Greece. The first 17 in Istanbul (Carrer et al., 2008). The London ‘outbreak’ strain
producer isolates were detected in 2002 among patients in belonged to the novel ST353 (C.P. Thomas and N. Woodford,
the intensive care units of three hospitals in Athens (Giakkou- unpublished data; http://www.pasteur.fr/recherche/genopole/
pi et al., 2003). These isolates had four different PFGE profiles PF8/mlst/Kpneumoniae.html). Recently, a gene predicted to
and isolates belonging to the two dominant PFGE ‘types’ had encode a novel OXA-48-like b-lactamase (with four amino
similar plasmids, containing a class 1 integron with blaVIM-1, acid differences) was detected in carbapenem-resistant isolates
aac6, dhfrI and aadA cassettes, indicating that horizontal of K. pneumoniae from three geographically dispersed centres
plasmid spread was occurring in addition to the spread of in India (Bell et al., 2009).
strains. Although most Greek K. pneumoniae with VIM As in other species, the emergence of carbapenemases in
enzymes are nonclonal, Ikonomidis et al. (2005) showed the K. pneumoniae limits therapeutic options. Polymyxins are
spread of a PFGE-related isolates with a similar integron to often regarded as agents of ‘last hope’ (Fernandez et al.,
two hospitals in other parts of Greece. As with plasmids 2010) and many carbapenemase-producing K. pneumoniae
encoding the KPC enzyme, those encoding VIM-1 have been isolates remain susceptible to them. However, resistance to
found in other Enterobacteriaceae (Miriagou et al., 2003a; colistin and polymyxin B is an emerging problem in the
Galani et al., 2007; Tsakris et al., 2007a, b). Currently, there are species, both in countries where the resistant isolates pre-
few MLST data for K. pneumoniae with VIM carbapenemases, dominantly belong to successful clones and in others where
although isolates belonging to ST383 have been reported in they are diverse. For example: (1) colistin-resistant isolates
Greece (Papagiannitsis et al., 2010) and to ST11 in Hungary of the usually susceptible ST258 clone with KPC carbapene-
(Kristof et al., 2010). As more MLST data become available, mase have been reported in the United States (Bratu et al.,
we may learn of the relationships among organisms that 2005b) and Greece (Zarkotou et al., 2010); (2) the first
appear to be unrelated by PFGE. ST258 isolate with the KPC enzyme in Hungary was
Recent reports describe K. pneumoniae isolates in Greece susceptible to colistin [minimal inhibitory concentration
that have both VIM and KPC enzymes (Giakkoupi et al., (MIC), 0.5 mg L1], eight further isolates were resistant
2009; Meletis et al., 2010; Pournaras et al., 2010; Zioga et al., (MICs, 16–32 mg L1) (Toth et al., 2010), indicating either
2010), again illustrating the potential for bacteria to carry that resistance can emerge rapidly or, perhaps, the reintro-
seemingly superfluous genetic baggage. These ‘double car- duction of a polymyxin-resistant variant; (3) 15 colistin-
bapenemase producers’ appear to represent the acquisition resistant K. pneumoniae isolates, none with KPC carbapene-
of blaKPC genes by strains that already had VIM enzymes mase, collected from four hospitals in South Korea during
(Zioga et al., 2010); the converse – acquisition of blaVIM by 2006–2007 represented 6.8% of the isolates sampled from
isolates of ST258 with KPC enzymes – has not yet been nine hospitals, but were diverse and belonged to 14 STs
reported. Isolates of any species producing multiple ac- (ST11, ST27, ST37, ST218, ST354, ST356, ST358, ST359,
quired carbapenemases have not yet been described widely ST363, ST364, ST365, ST366, ST367 and ST369) (Suh et al.,


on 12 February 2018
2010). Because polymyxin resistance involves mutations that In the other scheme (Bartual et al., 2005), reference strains
cause changes in lipopolysaccharide composition, control- of European clones I and II have STs of 12 and 6, respec-
ling the spread of the resistant strains is the key issue, rather tively; ST22, and SLVs clustered into CC22, belonging to
than the horizontal spread of their resistance genes. European clone II, have been reported widely (Fu et al.,
Recently, K. pneumoniae isolates with the NDM-1 (New 2010; Mugnier et al., 2010; Park et al., 2010). A sequence-
Delhi Metallo-carbapenemase) enzyme have been identified, based typing scheme based on three genes (ompA, csuE and
initially in Sweden (Yong et al., 2009) and subsequently in blaOXA-51-like) has also been described (Turton et al., 2007)
the United Kingdom and throughout the Indian subconti- (http://www.hpa-bioinformatics.org.uk/AB/home.php);
nent (Abdul Gafur, 2010; Deshpande et al., 2010; Kumar- multiplex PCRs based on this facilitate the rapid identifica-
asamy et al., 2010). Although there is evidence of strain tion of representatives of the main clonal lineages. Sequen-
spread in some cities (specifically Haryana) in the subconti- cing of the blaOXA-51-like gene alone has also been used
nent (Kumarasamy et al., 2010), there has been no large- (Hamouda et al., 2010).
scale investigation or comparison of NDM producers to The first description of the international lineages was based
date. Importation of producers to Europe, and more re- on comparisons of cell envelope protein profiling, ribotyping
cently to the United States (Anonymous, 2010), is often and AFLP genomic fingerprinting of epidemic and none-
associated with patients who have had prior contact with the pidemic A. baumannii strains from geographically distinct
healthcare systems in India or Pakistan, and most of the European hospitals (Dijkshoorn et al., 1996). Since then,
isolates have diverse PFGE profiles (Kumarasamy et al., there have been abundant reports of outbreaks due to
2010), meaning that the European and the United States sublineages of these clones, including the French AYE VEB-1
cases probably represent a near-random ‘sampling’ of strains strain (European clone I) (Naas et al., 2006), the United
present in different parts of the subcontinent. It is note- Kingdom OXA-23 clone 1 and the United Kingdom South
worthy, however, that the first-reported NDM-positive iso- East clone (European clone II) (Coelho et al., 2006). These
late (Yong et al., 2009), two isolates from Oman (Poirel et al., have each affected large numbers of hospitals. There are
2011a), and seven from Nairobi, Kenya (Poirel et al., 2011b), numerous other examples from many countries (Da Silva
all belonged to ST14, a member of the large CC292 complex. et al., 2007; Nemec et al., 2008; Giannouli et al., 2009;
Isolates with NDM-1 carbapenemase are extremely multi- Donnarumma et al., 2010; Fu et al., 2010). A few other CCs,
resistant: they typically harbour ESBLs and acquired AmpC distinct from European clones I to III, have been described.
enzymes besides the NDM MBL, thus conferring resistance They also include genetically similar isolates from diverse
to all b-lactams; they also produce 16S methylases, often geographical locations, clearly fitting the description of the
ArmA or RmtC, which confer resistance to all clinically term ‘clone’ as defined by Orskov & Orskov (1983). They
useful aminoglycosides. Most remain susceptible to poly- include a novel international clone (ST15). These clonal
myxins, although here too resistance has been observed in lineages have long been associated with multiple antibiotic
some isolates (Kumarasamy et al., 2010). resistances, and the selective advantage these confer appears
The international spread of bacteria, particularly K. to be driving their expansion (Diancourt et al., 2010). While
pneumoniae, with NDM or KPC carbapenemases represents the core genome of these lineages is stable, the accessory
one of the most pressing resistance-related public health genome is more fluid, and carbapenem resistance among
issues. Both have the potential to impact dramatically on these isolates has become common, usually by acquisition of
healthcare, although it is impossible to predict which will OXA carbapenemase genes (blaOXA-23-like, blaOXA-58-like,
rise to dominance. blaOXA-40-like, and blaOXA-143-like), although it may simply
involve insertion sequence-mediated upregulation of the
intrinsic blaOXA-51-like gene. These genes may be chromoso-
Acinetobacter baumannii mally or plasmid encoded (Poirel & Nordmann, 2006)
Two MLST schemes exist for A. baumannii (Bartual et al., (Higgins et al., 2010b) (Mugnier et al., 2010). There is a
2005; Diancourt et al., 2010) with only three loci in common geographical variation in the distribution of acquired
(http://pubmlst.org/abaumannii/ and http://www.pasteur. OXA genes, with blaOXA-58-like associated with Greece and
fr/recherche/genopole/PF8/mlst/Abaumannii.html). The Italy (Tsakris et al., 2008a; Di Popolo et al., 2011; Donnar-
population structure of clinical isolates of A. baumannii is umma et al., 2010), blaOXA-40-like with Spain and Portugal (da
dominated by three international clonal lineages known as Silva et al., 2004; Quinteira et al., 2007; Ruiz et al., 2007) and
European clones I, II and III, corresponding to CC1 blaOXA-23-like with Northern European countries, Asia and
(comprising ST1, ST7, ST8, ST19 and ST20), CC2 (compris- South America (Coelho et al., 2006; Lee et al., 2009; Mendes
ing ST2, ST45 and ST47) and CC3 (ST3 and ST14) in the et al., 2009; Zarrilli et al., 2009; Fu et al., 2010). Acinetobacter
MLST scheme of Diancourt et al. (2010), and with most baumannii isolates with VIM, IMP, SIM and NDM MBLs
outbreak strains belonging to the first two of these lineages. have also been reported (Lee et al., 2005; Poirel & Nordmann,


on 12 February 2018
2006; Tsakris et al., 2006; Chiu et al., 2010; Karthikeyan et al., lineage (Pitt et al., 1989, 1990). Members of this epidemic
2010). The ability of these clonal lineages to adapt to advances lineage cluster very tightly when analysed by a variety of
in antimicrobial therapy is likely to be a key factor in their methods (Mifsud et al., 1997; Pirnay et al., 2009). This clone
success. includes only clinical isolates and the evidence indicates that it
emerged during the 1980s, perhaps selected by heavy anti-
biotic use (Pirnay et al., 2009). The O12 lineage falls into P.
Pseudomonas aeruginosa aeruginosa CC/BURST Group (BG) 4 – in context, a CC or BG
Pseudomonas aeruginosa is a key host species for genes encod- comprises those STs that have at least five alleles in common.
ing metallo-carbapenemases, particularly, but not limited to, An eBURST representation (http://eburst.mlst.net) of the
VIM types. In contrast to the Enterobacteriaceae, carbapenem relationships between P. aeruginosa STs reported to harbour
resistance is not unusual in this species. It is intrinsically MBLs or ESBLs is shown in Fig. 3.
resistant to ertapenem and strains with horizontally acquired The most prevalent serotypes of P. aeruginosa are O11,
carbapenemases, such as VIM types, must be distinguished O12, O6 and O1, with O11 and O12 particularly common
against a larger background of isolates that are resistant to among multiresistant isolates (Pirnay et al., 2009). Giske
imipenem, meropenem and doripenem through mutations et al. (2006) performed MLST on P. aeruginosa isolates
leading to loss of OprD porin (imipenem) or a combination of with VIM MBLs from four European countries: Greece,
this mechanism with upregulation of efflux pumps, particu- Hungary, Italy and Sweden. All of the O12 isolates belonged
larly MexAB-OprM (meropenem and doripenem). to ST229 (BG 4), but included isolates with either VIM-2
An MLST scheme for P. aeruginosa was published in 2004 or VIM-4 carbapenemase; these VIM MBL variants are
(Curran et al., 2004) and there are currently 972 defined STs phylogenetically distinct and represent separate acquisition
(http://pubmlst.org/paeruginosa/). The species has a nonclo- events rather than evolution of the enzyme within the
nal and epidemic structure, and recombination has played an strain. In contrast to the relative uniformity shown by O12
important role in its evolution. Because of this, attempts to isolates, those of serotype O11 show greater genetic
infer the relationships between all except the most related diversity. Although the O11 isolates all belonged to BG 11,
groups are essentially meaningless (Curran et al., 2004). There those from Italy produced the VIM-1 enzyme and belonged
is a huge diversity of STs and, typically, a huge overlap between to ST227, whereas isolates from Greece, Hungary and
isolates from clinical and environmental sources (Wiehlmann Sweden produced the VIM-4 enzyme and belonged to the
et al., 2007). One clear exception to this generalization is the distinct, but related ST230 (Giske et al., 2006; Samuelsen
international, and frequently multiresistant, serotype O12 et al., 2010).
Fig. 3. eBURST analysis (http://eburst.mlst.net) to

show linked and unlinked STs for Pseudomonas
aeruginosa isolates reported in the MLST data-
base (http://www.pubmlst.org/paeruginosa) to
produce an MBL or ESBL (SLVs are linked lines and
DLVs enclosed within balloons).


on 12 February 2018
More recently, Samuelsen et al. (2010) found that isolates (Toleman et al., 2002; Murphy et al., 2003). Isolates belong-
of the international complexes CC111 (specifically, STs 111 ing to a single PFGE-defined strain have caused hospital
and 229; serotype O12; blaVIM-2; corresponding to CC/BG outbreaks throughout Brazil (Gales et al., 2003; Zavascki
4) and CC235 (STs 235 and 230; serotype O11; blaVIM-4; CC/ et al., 2005; Carvalho et al., 2006). This strain typically is
BG 11) accounted for 10 of 12 VIM-type MBL producers resistant to all antibiotics, except polymyxins (Carvalho
isolated in Norway and Sweden between 1999 and 2007. et al., 2006; Fonseca et al., 2010), although rare isolates may
These included importations from Greece, Cyprus and be susceptible even to carbapenems (Pellegrino et al., 2008). It
Denmark, although six of the eight O12, CC111 isolates harbours an integron with aacA4, blaOXA-56 and aadA7 cas-
represented onward transmission in Sweden. The remaining settes, and a putative transposase gene (Carvalho et al., 2006).
two VIM MBL-producing isolates were distinct and were The blaSPM-1 gene is not on this integron, and is probably
associated with repatriations from Ghana (ST233, serotype located on large (c. 400 kb) plasmids. These are not transferable
O6; blaVIM-2) – the first Norwegian MBL producer – and in vitro to E. coli or other P. aeruginosa recipients (Toleman
Tunisia (ST654; serotype O11; blaVIM-2) (Samuelsen et al., et al., 2002; Poirel et al., 2004), but have achieved some
2009a, 2010). The authors concluded that ‘both import of horizontal spread to other strains of P. aeruginosa in the clinic
successful international clones and local clonal expansion con- (Castanheira et al., 2008), but not (yet) to other genera. Some
tribute to the emergence of MBL-producing P. aeruginosa in isolates also produce RmtD, a 16S rRNA methyltransferase that
Scandinavia’. These two CCs also account for many of the VIM confers broad aminoglycoside resistance (Doi et al., 2007a, b;
MBL-producing isolates from Hungary (Libisch et al., 2008b), Castanheira et al., 2008).
although other lineages, such as serotype O4, ST175 and Most of the SPM-1 MBL-producing isolates, including
serotype O6, ST395, also have a countrywide distribution the main PFGE-defined strain, belong to ST277 (Fonseca
(Libisch et al., 2009). Pseudomonas aeruginosa with VIM-2 et al., 2010), which was previously identified from Austria
MBL and belonging to ST175 also caused a recent outbreak of and China, suggesting that it is likely to be a widespread
urinary tract infections in 11 patients in Germany (Elias et al., international clone. It has three known SLVs, STs 364
2009). VIM-type MBLs have been identified in STs 155, 179 (Austria), 659, 758 (China) and one DLV, ST 206 (Canada)
and 811 in Spain (http://pubmlst.org/paeruginosa). (http://www.pubmlst.net/paeruginosa). It is worth noting
The predicted founder of the BG 11 is ST235 (Fig. 3), that SPM-1 MBL has also been detected in ST235 (CC235;
which has been found in many other countries, including http://www.pubmlst.net/paeruginosa). Producers of SPM-1
Austria, Belgium, France, Greece, Hungary, Italy, Poland, MBL are distinct from other multiresistant Brazilian P.
Russia, Serbia, Singapore, Sweden and Turkey, in association aeruginosa isolates (Fonseca et al., 2010); these comparators,
not just with VIM enzymes but also with BEL-, IMP- OXA-, similarly, were susceptible only to polymyxins, but lacked
PER-, PSE- and SPM- b-lactamases (Empel et al., 2007; SPM-1 and belonged to the unrelated ST244, which,
Shevchenko & Edelstein, 2007; Edalucci et al., 2008; Lepsano- together with its SLVs and DLVs, represents another widely
vic et al., 2008; Libisch et al., 2008a; Duljasz et al., 2009; distributed lineage, having also been identified in China,
Viedma et al., 2009; Glupczynski et al., 2010; Juan et al., 2010). Poland and the United Kingdom (Empel et al., 2007)
Isolates belonging to a single PFGE-defined strain of ST235 (http://www.pubmlst.net/paeruginosa).
accounted for 50% of multiresistant P. aeruginosa collected in It is not known whether the non-Brazilian isolates of
a hospital in Madrid, and were susceptible only to polymyxins ST277 and related STs that are present in the MLST database
(Viedma et al., 2009). This strain harboured an integron with also produced SPM-1 MBL. However, we are aware of
cassettes that encoded both the GES-1 ESBL and the GES-5 only one report outside Brazil of a P. aeruginosa isolate with
carbapenemase, together with blaOXA-2 and three aminoglyco- the SPM-1 enzyme (el Salabi et al., 2010), and this was from
side resistance genes: aac(6 0 )-33, aacA4 and aadA1 (Viedma a patient who had been repatriated to Switzerland from
et al., 2009). a Brazilian hospital; the isolate was highly related by PFGE
Pseudomonas aeruginosa isolates with IMP-type MBLs are to SPM-1-positive comparators from Brazil. Given the
geographically scattered and belong to diverse STs. Those level of international interest in carbapenemase-producing
included in the MLST database include STs 235 and 357 bacteria and the inclusion of primers for blaSPM-1 in MBL
(IMP-1, Japan), 260 (IMP-14, Norway), 620 and 621 (IMP- screening assays (Ellington et al., 2007; Mendes et al., 2007),
22 and -13, respectively, Austria), 741, 742, 743 (IMP-1, it seems improbable that P. aeruginosa isolates with the
Singapore), 744, 745 (IMP-7, Singapore) and also STs 235, SPM-1 enzyme are widespread globally, even if ST277 is
593 and 654 (unspecified IMP alleles, Brazil and Singapore) prevalent. Rather, it seems likely that the acquisition of
(Duljasz et al., 2009; Kouda et al., 2009; Samuelsen et al., SPM-1 MBL is a feature limited to ST277 in Brazil, reflecting
2010) (http://pubmlst.org/paeruginosa; Fig. 3). the escape of the blaSPM-1 gene from an unidentified species
The first SPM-1 MBL-producing isolate of P. aeruginosa with subsequent national dissemination and a single exam-
was identified in Sao Paulo, Brazil, in the late 1990s ple of international transfer.


on 12 February 2018
Pseudomonas aeruginosa isolates from the lungs of cystic different parts of the globe, but we now recognize that some
fibrosis (CF) patients are often resistant to multiple anti- Gram-negative bacterial species include globally distributed
biotic classes, and in some cases are pan-resistant, including strains or clones and so we must be careful not to over-infer
to polymyxins. Long-term exposure of isolates in the CF direct relationships where there may be none. Prevalence
lung to antibiotics leads to the accumulation of mutations and/or wide geographic scatter may simply reflect a strain/
that confer highly complex phenotypes in strains with clone’s biological success and repeated acquisition of resis-
defective mismatch repair systems (Oliver et al., 2000). tance through convergent evolution (Deschamps et al.,
These mechanisms usually involve complex combinations 2009) rather than contemporaneous transmission events,
of reduced porin expression and upregulation of multiple although the latter must also occur.
efflux pumps and intrinsic b-lactamases (Lister et al., 2009; When considering multiresistance, one should be alert to
Wolter et al., 2009a; Tomas et al., 2010). Carbapenem this possibility when representatives of a single clone may
resistance is frequent, but there is, to our knowledge, only carry markedly different resistance genes; this probably
one report of MBL production by CF isolates with the VIM- indicates an ability to acquire whatever genes are locally
2 enzyme in Portugal (Cardoso et al., 2008). prevalent, rather than direct spread with repeated loss and
Although Curran et al. (2004) included many sputum gain of resistance genes. Conversely, ‘recent’ dissemination is
isolates in their original MLST study; no CF-specific analyses likely to have been a significant factor in epidemiological
were presented. The largest subsequent application of MLST success when representatives of a particular clone are found
specifically to CF isolates was undertaken by Waine et al. widely in combination with a specific resistance gene(s),
(2009), who found that most patients were colonized by although even here it may not indicate direct transmission.
isolates belonging to one (50%) or two (37.5%) STs, but up MLST is a definitive methodology that allows isolates
to four STs were present in some patients. Furthermore, anywhere to be typed and compared. However, it is expen-
these authors found that patients could be colonized simul- sive and many workers seek to introduce cheaper alterna-
taneously by unique STs and ‘epidemic’ STs, with the latter tives, such as VNTR/MLVA, to determine information about
including ST146 (the Liverpool strain, widespread in the relatedness. Unless the same next-generation approach is
United Kingdom) and ST148 (the Midlands 1 strain) widely adopted, there is potential for contrasting methodol-
(Waine et al., 2009). ogies to make interstudy comparisons (including with
Pirnay et al. (2009) recently investigated the contentious existing MLST data) more difficult or impossible. This is a
issue of CF-specific clones and concluded that there was cause for concern and, in our opinion, would be a retrograde
little evidence for them; multiresistant CF isolates from step. Clearly, we need to embrace alternative methods if they
different parts of the world were genotypically diverse and are faster, cheaper than and as powerful as MLST, but we
unlikely to be directly related, but clustered into a core must establish a comprehensive ‘dictionary’ to ‘translate’ the
lineage, rather than a true clone. The authors could find no clonal group designations of different schema. There is a
evidence for ‘widespread or global transmission of successful P. similar requirement where multiple MLST schemes exist for
aeruginosa CF strains’ and concluded that strains belonging a particular species; this has been at least partially addressed
to the core lineage were ubiquitous in the environment. The in some cases, for example, for E. coli (Jaureguy et al., 2008).
frequency at which particular strains are isolated from CF There are numerous examples in the literature of hospital
patients is likely to reflect the prevalence of these strains in and community outbreaks, in some instances substantial,
the local environment, and most patients will acquire the caused by MDR Gram-negatives for which there has been
strains independently (Pirnay et al., 2009); certainly mem- extensive molecular investigation, but for which there are no
bers of the Liverpool strain vary considerably in antibiogram MLST data. Hence, although local purposes are served,
among patients, ranging from fully susceptible to pan- much add-on value of potential national or international
resistant (Scott & Pitt, 2004). importance is lost. We would urge laboratories to undertake
MLST on representatives of all outbreak strains and to use it
in parallel with any other current or newly introduced
Concluding remarks method. Only by doing this can we generate a more
Inferring the relatedness of bacterial isolates based on typing complete picture and fuller understanding of the impor-
data is most straightforward when there is strong supportive tance of high-risk clones in the international dissemination
epidemiological evidence (e.g. an outbreak situation). It is of antibiotic resistance.
more difficult to interpret similarity (or even identity) with
confidence in the absence of such evidence, and especially
when isolates have seemingly disparate origins. It is easy to
Acknowledgements
fall into the trap of assuming that isolates with similar DNA No external funding was provided for this work. D.M.L. has
profiles must represent a transmission chain, although from received conference support from numerous pharmaceutical


on 12 February 2018
companies. He also holds shares in AstraZeneca, Merck, Klebsiella pneumoniae in New York City: a new threat to our
Pfizer, Dechra and GlaxoSmithKline and, as Executor, antibiotic armamentarium. Arch Intern Med 165: 1430–1435.
manages further holdings in GlaxoSmithKline and Eco Bratu S, Mooty M, Nichani S, Landman D, Gullans C, Pettinato
Animal Health. N.W. has received conference support and B, Karumudi U, Tolaney P & Quale J (2005c) Emergence of
has spoken at symposia sponsored by many pharmaceutical KPC-possessing Klebsiella pneumoniae in Brooklyn, New York:
companies. None of these declared interests poses a conflict epidemiology and recommendations for detection. Antimicrob
with the contents of this review. J.F.T., none to declare. Agents Ch 49: 3018–3020.
Bratu S, Brooks S, Burney S, Kochar S, Gupta J, Landman D &
Quale J (2007) Detection and spread of Escherichia coli
possessing the plasmid-borne carbapenemase KPC-2 in
References Brooklyn, New York. Clin Infect Dis 44: 972–975.
Brisse S, Fevre C, Passet V, Issenhuth-Jeanjean S, Tournebize R,
Abdul Gafur K (2010) An obituary – on the death of antibiotics.
Diancourt L & Grimont P (2009) Virulent clones of Klebsiella
J Assoc Physicians I 58: 143–144.
Akpaka PE, Swanston WH, Ihemere HN, Correa A, Torres JA, pneumoniae: identification and evolutionary scenario based on
Tafur JD, Montealegre MC, Quinn JP & Villegas MV (2009) genomic and phenotypic characterization. PLoS One 4: e4982.
Emergence of KPC-producing Pseudomonas aeruginosa in Cagnacci S, Gualco L, Debbia E, Schito GC & Marchese A (2008)
Trinidad and Tobago. J Clin Microbiol 47: 2670–2671. European emergence of ciprofloxacin-resistant Escherichia coli
Anonymous (2010) Detection of Enterobacteriaceae isolates clonal groups O25:H4-ST 131 and O15:K52:H1 causing
carrying metallo-beta-lactamase – United States, 2010. Morbid community-acquired uncomplicated cystitis. J Clin Microbiol
Mortal Wkly Rep 59: 750. 46: 2605–2612.
Baraniak A, Izdebski R, Herda M, Fiett J, Hryniewicz W, Cai JC, Zhou HW, Zhang R & Chen GX (2008) Emergence of
Gniadkowski M, Kern-Zdanowicz I, Filczak K & Lopaciuk U Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli
(2009) Emergence of Klebsiella pneumoniae ST258 with KPC-2 isolates possessing the plasmid-mediated carbapenem-
in Poland. Antimicrob Agents Ch 53: 4565–4567. hydrolyzing b-lactamase KPC-2 in intensive care units of a
Bartual SG, Seifert H, Hippler C, Luzon MAD, Wisplinghoff H & Chinese hospital. Antimicrob Agents Ch 52: 2014–2018.
Rodriguez-Valera F (2005) Development of a multilocus Canton R & Coque TM (2006) The CTX-M b-lactamase
sequence typing scheme for characterization of clinical isolates pandemic. Curr Opin Microbiol 9: 466–475.
of Acinetobacter baumannii. J Clin Microbiol 43: 4382–4390. Cardoso O, Alves AF & Leitao R (2008) Metallo-b-lactamase
Bell JM, Mathai D, Jones RN & Turnidge JD (2009) Emergence of VIM-2 in Pseudomonas aeruginosa isolates from a cystic
OXA-48 Carbapenemases among Klebsiella spp. from India. fibrosis patient. Int J Antimicrob Ag 31: 375–379.
Proceedings & abstracts of the 49th Interscience Conference on Carrer A, Poirel L, Eraksoy H, Cagatay AA, Badur S & Nordmann
Antimicrobial Agents & Chemotherapy, American Society for P (2008) Spread of OXA-48-positive carbapenem-resistant
Microbiology, San Francisco (abstract C2-650). Klebsiella pneumoniae isolates in Istanbul, Turkey. Antimicrob
Bennett JW, Herrera ML, Lewis JS II, Wickes BW & Jorgensen JH Agents Ch 52: 2950–2954.
(2009) KPC-2-producing Enterobacter cloacae and Carrer A, Poirel L, Yilmaz M, Akan OA, Feriha C, Cuzon G, Matar
Pseudomonas putida coinfection in a liver transplant recipient. G, Honderlick P & Nordmann P (2010) Spread of OXA-48-
Antimicrob Agents Ch 53: 292–294. encoding plasmid in Turkey and beyond. Antimicrob Agents Ch
Bert F, Johnson JR, Ouattara B, Leflon-Guibout V, Johnston B, 54: 1369–1373.
Marcon E, Valla D, Moreau R & Nicolas-Chanoine MH (2010) Carvalho AP, Albano RM, de Oliveira DN, Cidade DA, Teixeira
Genetic diversity and virulence profiles of Escherichia coli LM & Marques EA (2006) Characterization of an epidemic
isolates causing spontaneous bacterial peritonitis and carbapenem-resistant Pseudomonas aeruginosa producing
bacteremia in patients with cirrhosis. J Clin Microbiol 48: SPM-1 metallo-b-lactamase in a hospital located in Rio de
2709–2714. Janeiro, Brazil. Microb Drug Resist 12: 103–108.
Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman Castanheira M, Fritsche TR, Sader HS, Jones RN, Doi Y, Oliveira
D, Rahal JJ, Brooks S, Cebular S & Quale J (2004) Emergence Garcia D & Paterson DL (2008) RmtD 16S RNA methylase in
of carbapenem-resistant Klebsiella species possessing the class epidemiologically unrelated SPM-1-producing Pseudomonas
A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant aeruginosa isolates from Brazil. Antimicrob Agents Ch 52:
TEM-30 b-lactamases in New York City. Clin Infect Dis 39: 1587–1588.
55–60. Castanheira M, Watters AA, Smayevsky J, Casellas JM, Gur D,
Bratu S, Landman D, Alam M, Tolentino E & Quale J (2005a) Unal S & Jones RN (2009) Emergence of blaOXA-48 among
Detection of KPC carbapenem-hydrolyzing enzymes in Enterobacter cloacae in Argentina and its prevalence among
Enterobacter spp. from Brooklyn, New York. Antimicrob Agents carbapenem non-susceptible Enterobacteriaceae. Proceedings
Ch 49: 776–778. and Abstracts of the 49th Interscience Conference on
Bratu S, Landman D, Haag R, Recco R, Eramo A, Alam M & Antimicrobial Agents & Chemotherapy, American Society for
Quale J (2005b) Rapid spread of carbapenem-resistant Microbiology, San Francisco (abstract C2-647).


on 12 February 2018
Chiu CH, Lee HY, Tseng LY, Chen CL, Chia JH, Su LH & Liu SY Cuzon G, Naas T, Lesenne A, Benhamou M & Nordmann P
(2010) Mechanisms of resistance to ciprofloxacin, ampicillin/ (2010) Plasmid-mediated carbapenem-hydrolysing OXA-48
sulbactam and imipenem in Acinetobacter baumannii clinical b-lactamase in Klebsiella pneumoniae from Tunisia. Int J
isolates in Taiwan. Int J Antimicrob Ag 35: 382–386. Antimicrob Ag 36: 91–93.
Clermont O, Lavollay M, Vimont S, Deschamps C, Forestier C, Damjanova I, Toth A, Paszti J, Hajbel-Vekony G, Jakab M, Berta J,
Branger C, Denamur E & Arlet G (2008) The CTX-M-15- Milch H & Fuzi M (2008) Expansion and countrywide
producing Escherichia coli diffusing clone belongs to a highly dissemination of ST11, ST15 and ST147 ciprofloxacin-
virulent B2 phylogenetic subgroup. J Antimicrob Chemoth 61: resistant CTX-M-15-type b-lactamase-producing Klebsiella
1024–1028. pneumoniae epidemic clones in Hungary in 2005–the new
Clermont O, Dhanji H, Upton M et al. (2009) Rapid detection of ‘MRSAs’? J Antimicrob Chemoth 62: 978–985.
the O25b-ST131 clone of Escherichia coli encompassing the Da Silva G, Dijkshoorn L, van der RT, van Strijen B & Duarte A
CTX-M-15-producing strains. J Antimicrob Chemoth 64: (2007) Identification of widespread, closely related
274–277. Acinetobacter baumannii isolates in Portugal as a subgroup of
Coelho JM, Turton JF, Kaufmann ME et al. (2006) Occurrence of European clone II. Clin Microbiol Infec 13: 190–195.
carbapenem-resistant Acinetobacter baumannii clones at da Silva GJ, Quinteira S, Bertolo E, Sousa JC, Gallego L, Duarte A
multiple hospitals in London and Southeast England. J Clin & Peixe L (2004) Long-term dissemination of an OXA-40
Microbiol 44: 3623–3627. carbapenemase-producing Acinetobacter baumannii clone in
Coenye T, Spilker T, Martin A & LiPuma JJ (2002) Comparative the Iberian Peninsula. J Antimicrob Chemoth 54: 255–258.
assessment of genotyping methods for epidemiologic study of Deschamps C, Clermont O, Hipeaux MC, Arlet G, Denamur E &
Burkholderia cepacia genomovar III. J Clin Microbiol 40: Branger C (2009) Multiple acquisitions of CTX-M plasmids in
3300–3307.
the rare D2 genotype of Escherichia coli provide evidence for
Coque TM, Novais A, Carattoli A, Poirel L, Pitout J, Peixe L,
convergent evolution. Microbiology 155: 1656–1668.
Baquero F, Canton R & Nordmann P (2008) Dissemination of
Deshpande P, Rodrigues C, Shetty A, Kapadia F, Hedge A &
clonally related Escherichia coli strains expressing extended-
Soman R (2010) New Delhi Metallo-b-lactamase (NDM-1) in
spectrum b-lactamase CTX-M-15. Emerg Infect Dis 14:
Enterobacteriaceae: treatment options with carbapenems
195–200.
compromised. J Assoc Physicans I 58: 147–149.
Cremet L, Caroff N, Giraudeau C, Dauvergne S, Lepelletier D,
Dhanji H, Doumith M, Clermont O, Denamur E, Hope R,
Reynaud A & Corvec S (2010) Occurrence of ST23 complex
Livermore DM & Woodford N (2010) Real-time PCR for
phylogroup A Escherichia coli isolates producing extended-
detection of the O25b-ST131 clone of Escherichia coli and its
spectrum AmpC b-lactamase in a French hospital. Antimicrob
CTX-M-15-like extended-spectrum b-lactamases. Int J
Agents Ch 54: 2216–2218.
Antimicrob Ag 36: 355–358.
Curiao T, Morosini MI, Ruiz-Garbajosa P, Robustillo A, Baquero
Dhanji H, Murphy NM, Akhigbe C, Doumith M, Hope R,
F, Coque TM & Canton R (2010) Emergence of blaKPC-3-
Livermore DM & Woodford N (2011) Isolation of
Tn4401a associated with a pKPN3/4-like plasmid within
fluoroquinolone-resistant O25b:H4-ST131 Escherichia coli
ST384 and ST388 Klebsiella pneumoniae clones in Spain.
J Antimicrob Chemoth 65: 1608–1614. with CTX-M-14 extended-spectrum b-lactamase from UK
Curran B, Jonas D, Grundmann H, Pitt T & Dowson CG (2004) river water. J Antimicrob Chemoth 66: 512–516.
Development of a multilocus sequence typing scheme for the Diancourt L, Passet V, Verhoef J, Grimont PAD & Brisse S (2005)
opportunistic pathogen Pseudomonas aeruginosa. J Clin Multilocus sequence typing of Klebsiella pneumoniae
Microbiol 42: 5644–5649. nosocomial isolates. J Clin Microbiol 43: 4178–4182.
Cuzon G, Naas T, Bogaerts P, Glupczynski Y, Huang TD & Diancourt L, Passet V, Nemec A, Dijkshoorn L & Brisse S (2010)
Nordmann P (2008a) Plasmid-encoded carbapenem- The population structure of Acinetobacter baumannii:
hydrolyzing b-lactamase OXA-48 in an imipenem-susceptible expanding multiresistant clones from an ancestral susceptible
Klebsiella pneumoniae strain from Belgium. Antimicrob Agents genetic pool. PLoS One 5: e10034.
Ch 52: 3463–3464. Diaz MA, Hernandez-Bello JR, Rodriguez-Bano J, Martinez-
Cuzon G, Naas T, Demachy MC & Nordmann P (2008b) Martinez L, Calvo J, Blanco J & Pascual A & for the Spanish
Plasmid-mediated carbapenem-hydrolyzing b-lactamase Group for Nosocomial Infections (GEIH) (2010) Diversity of
KPC-2 in Klebsiella pneumoniae isolate from Greece. Escherichia coli strains producing extended-spectrum b-
Antimicrob Agents Ch 52: 796–797. lactamases in Spain: second nationwide study. J Clin Microbiol
Cuzon G, Naas T, Carrer A, Honderlick P, Cerf C & Nordmann P 48: 2840–2845.
(2009) Plasmid-mediated carbapenem-hydrolyzing b- Dijkshoorn L, Aucken H, Gerner-Smidt P, Janssen P, Kaufmann
lactamase OXA-48 in Klebsiella pneumoniae from Egypt. ME, Garaizar J, Ursing J & Pitt TL (1996) Comparison of
Proceedings and Abstracts of the 49th Interscience Conference on outbreak and nonoutbreak Acinetobacter baumannii strains by
Antimicrobial Agents & Chemotherapy, American Society for genotypic and phenotypic methods. J Clin Microbiol 34:
Microbiology, San Francisco (abstract C2-649). 1519–1525.


on 12 February 2018
Di Popolo A, Giannouli M, Triassi M, Brisse S & Zarrilli R (2011) Endimiani A, DePasquale JM, Forero S et al. (2009a) Emergence
Molecular epidemiological investigation of multidrug- of blaKPC-containing Klebsiella pneumoniae in a long-term
resistant Acinetobacter baumannii strains in four acute care hospital: a new challenge to our healthcare system.
Mediterranean countries with a multilocus sequence typing J Antimicrob Chemoth 64: 1102–1110.
scheme. Clin Microbiol Infec 17: 197–201. Endimiani A, Hujer AM, Perez F et al. (2009b) Characterization
Doi Y, Ghilardi ACR, Adams J, Oliveira Garcia D & Paterson DL of blaKPC-containing Klebsiella pneumoniae isolates detected
(2007a) High prevalence of metallo-b-lactamase and 16S in different institutions in the Eastern USA. J Antimicrob
rRNA methylase coproduction among imipenem-resistant Chemoth 63: 427–437.
Pseudomonas aeruginosa isolates in Brazil. Antimicrob Agents Ewers C, Grobbel M, Stamm I et al. (2010) Emergence of human
Ch 51: 3388–3390. pandemic O25:H4-ST131 CTX-M-15 extended-spectrum-b-
Doi Y, Oliveira Garcia D, Adams J & Paterson DL (2007b) lactamase-producing Escherichia coli among companion
Coproduction of novel 16S rRNA methylase RmtD and animals. J Antimicrob Chemoth 65: 651–660.
metallo-b-lactamase SPM-1 in a panresistant Pseudomonas Fam N, Leflon-Guibout V, Fouad S, Aboul-Fadl L, Marcon E,
aeruginosa isolate from Brazil. Antimicrob Agents Ch 51: Desouky D, El Defrawy I, Abou-Aitta A, Klena J & Nicolas-
852–856. Chanoine MH (2010) CTX-M-15-producing Escherichia coli
Donnarumma F, Sergi S, Indorato C et al. (2010) Molecular clinical isolates in Cairo (Egypt), including isolates of clonal
characterization of Acinetobacter isolates collected in intensive complex ST10 and clones ST131, ST73, and ST405 in both
care units of six hospitals in Florence, Italy, during a 3-year community and hospital settings. Microb Drug Resist. DOI: 10.
surveillance program: a population structure analysis. 1089/mdr.2010.0063.
J Clin Microbiol 48: 1297–1304. Feil EJ, Li BC, Aanensen DM, Hanage WP & Spratt BG (2004)
Duljasz W, Gniadkowski M, Sitter S, Wojna A & Jebelean C eBURST: inferring patterns of evolutionary descent among
(2009) First organisms with acquired metallo-b-lactamases clusters of related bacterial genotypes from multilocus
(IMP-13, IMP-22, and VIM-2) reported in Austria. Antimicrob sequence typing data. Bacteriol 186: 1518–1530.
Agents Ch 53: 2221–2222. Fernandez L, Gooderham WJ, Bains M, McPhee JB, Wiegand I &
Edalucci E, Spinelli R, Dolzani L, Riccio ML, Dubois V, Tonin EA, Hancock REW (2010) Adaptive resistance to the ‘Last Hope’
Rossolini GM & Lagatolla C (2008) Acquisition of different antibiotics polymyxin B and colistin in Pseudomonas
carbapenem resistance mechanisms by an epidemic clonal aeruginosa is mediated by the novel two-component
lineage of Pseudomonas aeruginosa. Clin Microbiol Infec 14: regulatory system ParR-ParS. Antimicrob Agents Ch 54:
88–90. 3372–3382.
Elias J, Schoen C, Heinze G, Valenza G, Gerharz E, Riedmiller H & Fonseca ELd, Freitas FdS & Vicente ACP (2010) The colistin-
Vogel U (2009) Nosocomial outbreak of VIM-2 metallo- only-sensitive Brazilian Pseudomonas aeruginosa clone SP
b-lactamase producing Pseudomonas aeruginosa associated (sequence type 277) is spread worldwide. Antimicrob Agents
with retrograde urography. Clin Microbiol Infec. DOI: 10.1111/ Ch 54: 2743.
j.1469-0691.2009.03146.x. Fu Y, Zhou J, Zhou H, Yang Q, Wei Z, Yu Y & Li L (2010) Wide
Ellington MJ, Kistler J, Livermore DM & Woodford N (2007) dissemination of OXA-23-producing carbapenem-resistant
Multiplex PCR for rapid detection of genes encoding acquired Acinetobacter baumannii clonal complex 22 in multiple cities
metallo-b-lactamases. J Antimicrob Chemoth 59: 321–322. of China. J Antimicrob Chemoth 65: 644–650.
el Salabi A, Toleman MA, Weeks J, Bruderer T, Frei R & Walsh TR Galani I, Souli M, Koratzanis E, Koratzanis G, Chryssouli Z &
(2010) First report of the metallo-b-lactamase SPM-1 in Giamarellou H (2007) Emerging bacterial pathogens:
Europe. Antimicrob Agents Ch 54: 582. Escherichia coli, Enterobacter aerogenes and Proteus mirabilis
Empel J, Filczak K, Mrowka A, Hryniewicz W, Livermore DM & clinical isolates harbouring the same transferable plasmid
Gniadkowski M (2007) Outbreak of Pseudomonas aeruginosa coding for metallo-b-lactamase VIM-1 in Greece. J Antimicrob
Infections with PER-1 extended-spectrum b-lactamase in Chemoth 59: 578–579.
Warsaw, Poland: further evidence for an international clonal Gales AC, Menezes LC, Silbert S & Sader HS (2003)
complex. J Clin Microbiol 45: 2829–2834. Dissemination in distinct Brazilian regions of an epidemic
Ender PT, Gajanana D, Johnston B, Clabots C, Tamarkin FJ & carbapenem-resistant Pseudomonas aeruginosa producing
Johnson JR (2009) Transmission of an extended-spectrum-b- SPM metallo-b-lactamase. J Antimicrob Chemoth 52: 699–702.
lactamase-producing Escherichia coli (sequence type ST131) Giakkoupi P, Xanthaki A, Kanelopoulou M et al. (2003) VIM-1
strain between a father and daughter resulting in septic shock metallo-b-lactamase-producing Klebsiella pneumoniae strains
and emphysematous pyelonephritis. J Clin Microbiol 47: in Greek hospitals. J Clin Microbiol 41: 3893–3896.
3780–3782. Giakkoupi P, Pappa O, Polemis M, Vatopoulos AC, Miriagou V,
Endimiani A, Carias LL, Hujer AM et al. (2008) Presence of Zioga A, Papagiannitsis CC & Tzouvelekis LS (2009)
plasmid-mediated quinolone resistance in Klebsiella Emerging Klebsiella pneumoniae co-producing KPC-2
pneumoniae isolates possessing blaKPC in the United States. and VIM-1 carbapenemases VIM-1 carbapenemases.
Antimicrob Agents Ch 52: 2680–2682. Antimicrob Agents Ch 53: 4048–4050.


on 12 February 2018
Giakkoupi P, Maltezou H, Polemis M, Pappa O, Saroglou G & Higgins PG, Poirel L, Lehmann M, Nordmann P & Seifert H
Vatopoulos A (2009) KPC-2-producing Klebsiella pneumoniae (2009) OXA-143, a novel carbapenem-hydrolyzing class D b-
infections in Greek hospitals are mainly due to a lactamase in Acinetobacter baumannii. Antimicrob Agents Ch
hyperepidemic clone. Euro Surveill 14: pii 19218. 53: 5035–5038.
Giannouli M, Tomasone F, Agodi A, Vahaboglu H, Daoud Z, Higgins PG, Dammhayn C, Hackel M & Seifert H (2010a) Global
Triassi M, Tsakris A & Zarrilli R (2009) Molecular spread of carbapenem-resistant Acinetobacter baumannii.
epidemiology of carbapenem-resistant Acinetobacter J Antimicrob Chemoth 65: 233–238.
baumannii strains in intensive care units of multiple Higgins PG, Lehmann M & Seifert H (2010b) Inclusion of OXA-
Mediterranean hospitals. J Antimicrob Chemoth 63: 828–830. 143 primers in a multiplex polymerase chain reaction (PCR)
Giske CG, Libisch B, Colinon C, Scoulica E, Pagani L, Fuzi M, for genes encoding prevalent OXA carbapenemases in
Kronvall G & Rossolini GM (2006) Establishing clonal Acinetobacter spp. Int J Antimicrob Ag 35: 305.
relationships by multilocus sequence typing between VIM-1- Hossain A, Ferraro MJ, Pino RM, Dew RB III, Moland ES,
like metallo-b-lactamase-producing Pseudomonas aeruginosa Lockhart TJ, Thomson KS, Goering RV & Hanson ND (2004)
from four European countries. J Clin Microbiol 44: 4309–4315. Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 in
Glupczynski Y, Bogaerts P, Deplano A, Berhin C, Huang TD, van an Enterobacter sp. Antimicrob Agents Ch 48: 4438–4440.
Eldere J & Rodriguez-Villalobos H (2010) Detection and Ikonomidis A, Tokatlidou D, Kristo I, Sofianou D, Tsakris A,
characterization of class A extended-spectrum-b-lactamase- Mantzana P, Pournaras S & Maniatis AN (2005) Outbreaks in
producing Pseudomonas aeruginosa isolates in Belgian distinct regions due to a single Klebsiella pneumoniae clone
hospitals. J Antimicrob Chemoth 65: 866–871. carrying a blaVIM-1 metallo-b-lactamase gene. J Clin
Goldfarb D, Harvey SB, Jessamine K, Jessamine P, Toye B & Microbiol 43: 5344–5347.
Desjardins M (2009) Detection of plasmid-mediated KPC- Jaureguy F, Landraud L, Passet V et al. (2008) Phylogenetic and
genomic diversity of human bacteremic Escherichia coli strains.
producing Klebsiella pneumoniae in Ottawa, Canada: evidence
BMC Genomics 9: 560.
of intrahospital transmission. J Clin Microbiol 47: 1920–1922.
Johnson JR, Miller S, Johnston B, Clabots C & DebRoy C (2009)
Goren MG, Chmelnitsky I, Carmeli Y & Navon-Venezia S (2009)
Sharing of Escherichia coli sequence type ST131 and other
First report of plasmid encoded OXA-48-like carbapenemase
multidrug-resistant and urovirulent E. coli strains among dogs
in Escherichia coli from Israel. Proceedings and Abstracts of the
and cats within a household. J Clin Microbiol 47: 3721–3725.
49th Interscience Conference on Antimicrobial Agents &
Johnson JR, Johnston B, Clabots C, Kuskowski MA & Castanheira
Chemotherapy, American Society for Microbiology, San
M (2010) Escherichia coli sequence type ST131 as the major
Francisco (abstract C1-1765).
cause of serious multidrug-resistant E. coli infections in the
Goren MG, Navon-Venezia S, Chmelnitsky I & Carmeli Y (2010)
United States. Clin Infect Dis 51: 286–294.
Carbapenem-resistant KPC-2-producing Escherichia coli in a
Jones GL, Warren RE, Skidmore SJ, Davies VA, Gibreel T &
Tel Aviv Medical Center, 2005 to 2008. Antimicrob Agents Ch
Upton M (2008) Prevalence and distribution of plasmid-
54: 2687–2691.
mediated quinolone resistance genes in clinical isolates of
Guenther S, Grobbel M, Beutlich J, Guerra B, Ulrich RG, Wieler
Escherichia coli lacking extended-spectrum {beta}-lactamases.
LH & Ewers C (2010) Detection of pandemic B2-O25-ST131
J Antimicrob Chemoth 62: 1245–1251.
Escherichia coli harbouring the CTX-M-9 extended-spectrum Juan C, Zamorano L, Mena A, Alberti S, Perez JL & Oliver A
b-lactamase type in a feral urban brown rat (Rattus (2010) Metallo-b-lactamase-producing Pseudomonas putida as
norvegicus). J Antimicrob Chemoth 65: 582–584. a reservoir of multidrug resistance elements that can be
Guillouzouic A, Caroff N, Dauvergne S, Lepelletier D, Perrin transferred to successful Pseudomonas aeruginosa clones.
Guyomard A, Kempf I, Reynaud A & Corvec S (2009) MLST J Antimicrob Chemoth 65: 474–478.
typing of Escherichia coli isolates overproducing AmpC b- Karisik E, Ellington MJ, Livermore DM & Woodford N (2008)
lactamase. J Antimicrob Chemoth 63: 1290–1292. Virulence factors in Escherichia coli with CTX-M-15 and other
Gulmez D, Woodford N, Palepou MF, Mushtaq S, Metan G, extended-spectrum b-lactamases in the UK. J Antimicrob
Yakupogullari Y, Kocagoz S, Uzun O, Hascelik G & Livermore Chemoth 61: 54–58.
DM (2008) Carbapenem-resistant Escherichia coli and Karthikeyan K, Thirunarayan MA & Krishnan P (2010)
Klebsiella pneumoniae isolates from Turkey with OXA-48-like Coexistence of blaOXA-23 with blaNDM-1 and armA in
carbapenemases and outer membrane protein loss. Int J clinical isolates of Acinetobacter baumannii from India.
Antimicrob Ag 31: 523–526. J Antimicrob Chemoth 65: 2253–2254.
Hamouda A, Evans BA, Towner KJ & Amyes SGB (2010) Kassis-Chikhani N, Decre D, Ichai P, Sengelin C, Geneste D,
Characterization of epidemiologically unrelated Acinetobacter Mihaila L, Dussaix E & Arlet G (2010) Outbreak of Klebsiella
baumannii isolates from four continents by use of multilocus pneumoniae producing KPC-2 and SHV-12 in a French
sequence typing, pulsed-field gel electrophoresis, and hospital. J Antimicrob Chemoth 65: 1539–1540.
sequence-based typing of blaOXA-51-like genes. J Clin Microbiol Kendall EA, Chowdhury F, Begum Y et al. (2010) Relatedness of
48: 2476–2483. Vibrio cholerae O1/O139 from patients and their household


on 12 February 2018
contacts, determined by multilocus variable number tandem Leflon-Guibout V, Blanco J, Amaqdouf K, Mora A, Guize L &
repeat analysis (MLVA). J Bacteriol 192: 4367–4376. Nicolas-Chanoine MH (2008) Absence of CTX-M enzymes
Kitchel B, Rasheed JK, Patel JB, Srinivasan A, Navon-Venezia S, but high prevalence of clones, including clone ST131, among
Carmeli Y, Brolund A & Giske CG (2009a) Molecular fecal Escherichia coli isolates from healthy subjects living in the
epidemiology of KPC-producing Klebsiella pneumoniae area of Paris, France. J Clin Microbiol 46: 3900–3905.
isolates in the United States: clonal expansion of multilocus Lepsanovic Z, Libisch B, Tomanovic B, Nonkovici Z, Balogh B &
sequence type 258. Antimicrob Agents Ch 53: 3365–3370. Fuzi M (2008) Characterisation of the first VIM metallo-b-
Kitchel B, Sundin DR & Patel JB (2009b) Regional dissemination lactamase-producing Pseudomonas aeruginosa clinical isolate
of KPC-producing Klebsiella pneumoniae. Antimicrob Agents in Serbia. Acta Microbiol Immunol Hung 55: 447–454.
Ch 53: 4511–4513. Lescat M, Calteau A, Hoede C, Barbe V, Touchon M, Rocha E,
Ko KS, Lee JY, Baek JY et al. (2010) Predominance of an ST11 Tenaillon O, Medigue C, Johnson JR & Denamur E (2009) A
extended-spectrum b-lactamase-producing Klebsiella module located at a chromosomal integration hot spot is
pneumoniae clone causing bacteraemia and urinary tract responsible for the multidrug resistance of a reference strain
infections in Korea. Journal of Medical Microbiology 59: from Escherichia coli Clonal Group A. Antimicrob Agents Ch
822–828. 53: 2283–2288.
Kouda S, Ohara M, Onodera M et al. (2009) Increased prevalence Lewis T, Loman NJ, Bingle L, Jumaa P, Weinstock GM, Mortiboy
and clonal dissemination of multidrug-resistant Pseudomonas D & Pallen MJ (2010) High-throughput whole-genome
aeruginosa with the blaIMP-1 gene cassette in Hiroshima. sequencing to dissect the epidemiology of Acinetobacter
J Antimicrob Chemoth 64: 46–51. baumannii isolates from a hospital outbreak. J Hosp Infect 75:
Kristof K, Toth A, Damjanova I et al. (2010) Identification of a 37–41.
blaVIM-4 gene in the internationally successful Klebsiella Li W, Ye C, Jing H et al. (2010) Streptococcus suis outbreak
pneumoniae ST11 clone and in a Klebsiella oxytoca strain in investigation using multiple-locus variable tandem repeat
number analysis. Microbiol Immunol 54: 380–388.
Hungary. J Antimicrob Chemoth 65: 1303–1305.
Libisch B, Poirel L, Lepsanovic Z, Mirovic V, Balogh B, Paszti J,
Kumarasamy KK, Toleman MA, Walsh TR et al. (2010)
Hunyadi Z, Dobak A, Fuzi M & Nordmann P (2008a)
Emergence of a new antibiotic resistance mechanism in India,
Identification of PER-1 extended-spectrum b-lactamase
Pakistan, and the UK: a molecular, biological, and
producing Pseudomonas aeruginosa clinical isolates of the
epidemiological study. Lancet Infect Dis 10: 597–602.
international clonal complex CC11 from Hungary and Serbia.
Lau SH, Kaufmann ME, Livermore DM et al. (2008a) UK
FEMS Immunol Med Mic 54: 330–338.
epidemic Escherichia coli strains A-E, with CTX-M-15 b-
Libisch B, Watine J, Balogh B, Gacs M, Muzslay M, Szabo G &
lactamase, all belong to the international O25:H4-ST131
Fuzi M (2008b) Molecular typing indicates an important role
clone. J Antimicrob Chemoth 62: 1241–1244.
for two international clonal complexes in dissemination of
Lau SH, Reddy S, Cheesbrough J, Bolton FJ, Willshaw G, Cheasty
VIM-producing Pseudomonas aeruginosa clinical isolates in
T, Fox AJ & Upton M (2008b) Major uropathogenic
Hungary. Res Microbiol 159: 162–168.
Escherichia coli strain isolated in the Northwest of England
Libisch B, Balogh B & Fuzi M (2009) Identification of two
identified by multilocus sequence typing. J Clin Microbiol 46:
multidrug-resistant Pseudomonas aeruginosa clonal lineages
1076–1080. with a countrywide distribution in Hungary. Curr Microbiol
Leavitt A, Navon-Venezia S, Chmelnitsky I, Schwaber MJ &
58: 111–116.
Carmeli Y (2007) Emergence of KPC-2 and KPC-3 in Ligozzi M, Fontana R, Aldegheri M, Scalet G & Lo CG (2010)
carbapenem-resistant Klebsiella pneumoniae strains in an Comparative evaluation of an automated repetitive-sequence-
Israeli hospital. Antimicrob Agents C 51: 3026–3029. based PCR instrument versus pulsed-field gel electrophoresis
Leavitt A, Carmeli Y, Chmelnitsky I, Goren MG, Ofek I & Navon- in the setting of a Serratia marcescens nosocomial infection
Venezia S (2010) Molecular epidemiology, sequence types, and outbreak. J Clin Microbiol 48: 1690–1695.
plasmid analyses of KPC-producing Klebsiella pneumoniae Lindstedt BA (2005) Multiple-locus variable number tandem
strains in Israel. Antimicrob Agents Ch 54: 3002–3006. repeats analysis for genetic fingerprinting of pathogenic
Lee K, Yum JH, Yong D, Lee HM, Kim HD, Docquier JD, bacteria. Electrophoresis 26: 2567–2582.
Rossolini GM & Chong Y (2005) Novel acquired metallo-b- Lister PD, Wolter DJ & Hanson ND (2009) Antibacterial-resistant
lactamase gene, blaSIM-1, in a class 1 integron from Pseudomonas aeruginosa: clinical impact and complex
Acinetobacter baumannii clinical isolates from Korea. regulation of chromosomally encoded resistance mechanisms.
Antimicrob Agents Ch 49: 4485–4491. Clin Microbiol Rev 22: 582–610.
Lee K, Kim MN, Choi TY, Cho SE, Lee S, Whang DH, Yong D, Livermore DM, Canton R, Gniadkowski M et al. (2007) CTX-M:
Chong Y, Woodford N & Livermore DM (2009) Wide changing the face of ESBLs in Europe. J Antimicrob Chemoth
dissemination of OXA-type carbapenemases in clinical 59: 165–174.
Acinetobacter spp. isolates from South Korea. Int J Antimicrob Long SG, DuPont HL, Gaul L, Arafat RR, Selwyn BJ, Rogers J &
Ag 33: 520–524. Casey E (2010) Pulsed-field gel electrophoresis for Salmonella


on 12 February 2018
infection surveillance, Texas, USA, 2007. Emerg Infect Dis 16: Moland ES, Hong SG, Thomson KS, Larone DH & Hanson ND
983–985. (2007) Klebsiella pneumoniae isolate producing at least eight
Mammina C, Palma DM, Bonura C, Anna Plano MR, Monastero different b-lactamases, including AmpC and KPC b-
R, Sodano C, Cala C & Tetamo R (2010) Outbreak of infection lactamases. Antimicrob Agents Ch 51: 800–801.
with Klebsiella pneumoniae sequence type 258 producing Monteiro J, Santos AF, Asensi MD, Peirano G & Gales AC (2009)
Klebsiella pneumoniae carbapenemase 3 in an intensive care First report of KPC-2-producing Klebsiella pneumoniae strains
unit in Italy. J Clin Microbiol 48: 1506–1507. in Brazil. Antimicrob Agents Ch 53: 333–334.
Manges AR, Johnson JR, Foxman B, O’Bryan TT, Fullerton KE & Mora A, Blanco M, López C et al. (2011) Emergence of clonal
Riley LW (2001) Widespread distribution of urinary tract groups O1:HNM-D-ST59, O15:H1-D-ST393, O20:H34/
infections caused by a multidrug-resistant Escherichia coli HNM-D-ST354, O25b:H4-B2-ST131 and ONT:H21,42-B1-
clonal group. New Engl J Med 345: 1007–1013. ST101 among CTX-M-14-producing Escherichia coli clinical
Martin O, Valverde A, Morosini MI, Rodriguez-Dominguez M, isolates in Galicia, northwest Spain. Int J Antimicrob Ag 37:
Rodriguez-Banos M, Coque TM, Canton R & del Campo R 16–21.
(2010) Population analysis and epidemiological features of Mugnier PD, Poirel L, Naas T & Nordmann P (2010) Worldwide
inhibitor-resistant-TEM-b-lactamase-producing Escherichia dissemination of the blaOXA-23 carbapenemase gene of
coli isolates from both community and hospital settings in Acinetobacter baumannii. Emerg Infect Dis 16: 35–40.
Madrid, Spain. J Clin Microbiol 48: 2368–2372. Murphy TA, Simm AM, Toleman MA, Jones RN & Walsh TR
Meletis G, Tzampaz E, Protonotariou E & Sofianou D (2010) (2003) Biochemical characterization of the acquired metallo-
Emergence of Klebsiella pneumoniae carrying blaVIM and b-lactamase SPM-1 from Pseudomonas aeruginosa. Antimicrob
blaKPC genes. Hippokratia 14: 139–140. Agents Ch 47: 582–587.
Mendes RE, Kiyota KA, Monteiro J, Castanheira M, Andrade SS, Naas T, Nordmann P, Vedel G & Poyart C (2005) Plasmid-
mediated carbapenem-hydrolyzing b-lactamase KPC in a
Gales AC, Pignatari ACC & Tufik S (2007) Rapid detection and
Klebsiella pneumoniae isolate from France. Antimicrob Agents
identification of metallo-b-lactamase encoding genes by
Ch 49: 4423–4424.
multiplex real-time PCR assay and melt curve analysis. J Clin
Naas T, Coignard B, Carbonne A, Blanckaert K, Bajolet O, Bernet
Microbiol 45: 544–577.
C, Verdeil X, Astagneau P, Desenclos JC & Nordmann P (2006)
Mendes RE, Bell JM, Turnidge JD, Yang Q, Yu Y, Sun Z & Jones
VEB-1 extended-spectrum b-lactamase-producing
RN (2008) Carbapenem-resistant isolates of Klebsiella
Acinetobacter baumannii, France. Emerg Infect Dis 12:
pneumoniae in China and detection of a conjugative plasmid
1214–1222.
(blaKPC-2 plus qnrB4) and a blaIMP-4 gene. Antimicrob
Navon-Venezia S, Chmelnitsky I, Leavitt A, Schwaber MJ,
Agents Ch 52: 798–799.
Schwartz D & Carmeli Y (2006) Plasmid-mediated imipenem-
Mendes RE, Bell JM, Turnidge JD, Castanheira M & Jones RN
hydrolyzing enzyme KPC-2 among multiple carbapenem-
(2009) Emergence and widespread dissemination of OXA-23, -
resistant Escherichia coli clones in Israel. Antimicrob Agents Ch
24/40 and -58 carbapenemases among Acinetobacter spp. in
50: 3098–3101.
Asia-Pacific nations: report from the SENTRY Surveillance Navon-Venezia S, Leavitt A, Schwaber MJ, Rasheed JK, Srinivasan
Program. J Antimicrob Chemoth 63: 55–59. A, Patel JB & Carmeli Y & and the Israeli KPC Kpn Study
Mifsud AJ, Watine J, Picard B, Charet JC, Solignac-Bourrel C & Group. (2009) First report on a hyperepidemic clone of KPC-
Pitt TL (1997) Epidemiologically related and unrelated strains 3-producing Klebsiella pneumoniae in Israel genetically related
of Pseudomonas aeruginosa serotype O12 cannot be to a strain causing outbreaks in the United States. Antimicrob
distinguished by phenotypic and genotypic typing. J Hosp Agents Ch 53: 818–820.
Infect 36: 105–116. Nemec A, Krizova L, Maixnerova M, Diancourt L, van der
Mihaila L, Wyplosz B, Clermont O, Garry L, Hipeaux MC, Reijden TJK, Brisse S, van den Broek P & Dijkshoorn L (2008)
Vittecoq D, Dussaix E, Denamur E & Branger C (2010) Emergence of carbapenem resistance in Acinetobacter
Probable intrafamily transmission of a highly virulent CTX- baumannii in the Czech Republic is associated with the spread
M-3-producing Escherichia coli belonging to the emerging of multidrug-resistant strains of European clone II.
phylogenetic subgroup D2 O102-ST405 clone. J Antimicrob J Antimicrob Chemoth 62: 484–489.
Chemoth 65: 1537–1539. Nicolas-Chanoine MH, Blanco J, Leflon-Guibout V, Demarty R,
Miriagou V, Tzelepi E, Gianneli D & Tzouvelekis LS (2003a) Alonso MP, Caniça M, Park Y-J, Lavigne J-P, Pitout J &
Escherichia coli with a self-transferable, multiresistant plasmid Johnson JR (2008) Intercontinental emergence of Escherichia
coding for metallo-b-lactamase VIM-1. Antimicrob Agents Ch coli clone O25:H4-ST131 producing CTX-M-15. J Antimicrob
47: 395–397. Chemoth 61: 273–281.
Miriagou V, Tzouvelekis LS, Rossiter S, Tzelepi E, Angulo FJ & Niemann S, Koser CU, Gagneux S et al. (2009) Genomic diversity
Whichard JM (2003b) Imipenem resistance in a Salmonella among drug sensitive and multidrug resistant isolates of
clinical strain due to plasmid-mediated class A carbapenemase Mycobacterium tuberculosis with identical DNA fingerprints.
KPC-2. Antimicrob Agents Ch 47: 1297–1300. PLoS One 4: e7407.


on 12 February 2018
Oliver A, Canton R, Campo P, Baquero F & Blazquez J (2000) dissemination potential of the extremely broad-spectrum class
High frequency of hypermutable Pseudomonas aeruginosa in A b-lactamase KPC-2 identified in an Escherichia coli strain
cystic fibrosis lung infection. Science 288: 1251–1254. and an Enterobacter cloacae strain isolated from the same
Orskov F & Orskov I (1983) From the national institutes of patient in France. Antimicrob Agents Ch 52: 3725–3736.
health. Summary of a workshop on the clone concept in the Pirnay JP, Bilocq F, Pot B et al. (2009) Pseudomonas aeruginosa
epidemiology, taxonomy, and evolution of the population structure revisited. PLoS One 4: e7740.
enterobacteriaceae and other bacteria. J Infect Dis 148: Pitt TL, Livermore DM, Pitcher D, Vatopoulos AC & Legakis NJ
346–357. (1989) Multiresistant serotype O 12 Pseudomonas aeruginosa:
Oteo J, Cercenado E, Cuevas O, Bautista V, Delgado-Iribarren A, evidence for a common strain in Europe. Epidemiol Infect 103:
Orden B, Perez-Vazquez M, Garcia-Cobos S & Campos J 565–576.
(2010a) AmpC beta-lactamases in Escherichia coli: emergence Pitt TL, Livermore DM, Miller G, Vatopoulos A & Legakis NJ
of CMY-2-producing virulent phylogroup D isolates (1990) Resistance mechanisms of multiresistant serotype 012
belonging mainly to STs 57, 115, 354, 393, and 420, and Pseudomonas aeruginosa isolated in Europe. J Antimicrob
phylogroup B2 isolates belonging to the international clone Chemoth 26: 319–328.
O25b-ST131. Diagn Microbiol Infect Dis 67: 270–276. Platell JL, Cobbold RN, Johnson JR & Trott DJ (2010) Clonal
Oteo J, Perez-Vazquez M & Campos J (2010b) Extended- group distribution of fluoroquinolone-resistant Escherichia
spectrum b-lactamase producing Escherichia coli: changing coli among humans and companion animals in Australia.
epidemiology and clinical impact. Curr Opin Infect Dis 23: J Antimicrob Chemoth 65: 1936–1938.
320–326. Poirel L & Nordmann P (2006) Carbapenem resistance in
Oteo Js, Diestra K, Juan C et al. (2009) Extended-spectrum b- Acinetobacter baumannii: mechanisms and epidemiology. Clin
lactamase-producing Escherichia coli in Spain belong to a large Microbiol Infec 12: 826–836.
variety of multilocus sequence typing types, including ST10 Poirel L, Magalhaes M, Lopes M & Nordmann P (2004)
complex/A, ST23 complex/A and ST131/B2. Int J Antimicrob Molecular analysis of metallo-b-lactamase gene blaSPM-1-
Ag 34: 173–176. surrounding sequences from disseminated Pseudomonas
Ozawa M, Baba K & Asai T (2010) Molecular typing of avian aeruginosa isolates in Recife, Brazil. Antimicrob Agents Ch 48:
pathogenic Escherichia coli O78 strains in Japan by using 1406–1409.
multilocus sequence typing and pulsed-field gel Poirel L, Hombrouck-Alet C, Freneaux C, Bernabeu S &
electrophoresis. J Vet Med Sci 72: 1517–1520. Nordmann P (2010a) Global spread of New Delhi metallo-b-
Papagiannitsis CC, Giakkoupi P, Vatopoulos AC, Tryfinopoulou lactamase 1. Lancet Infect Dis 10: 832.
K, Miriagou V & Tzouvelekis LS (2010) Emergence of Poirel L, Nordmann P, Lagrutta E, Cleary T & Munoz-Price LS
Klebsiella pneumoniae of a novel sequence type (ST383) (2010b) Emergence of KPC-producing Pseudomonas
producing VIM-4, KPC-2 and CMY-4 b-lactamases. Int J aeruginosa in the United States. Antimicrob Agents Ch 54: 3072.
Antimicrob Ag 36: 573–574. Poirel L, Al Maskari Z, Al Rashdi F, Bernabeu S & Nordmann P
Park YK, Lee GH, Baek JY, Chung DR, Peck KR, Song JH & Ko KS (2011a) NDM-1-producing Klebsiella pneumoniae isolated in
(2010) A single clone of Acinetobacter baumannii, ST22, is the Sultanate of Oman. J Antimicrob Chemoth 66: 304–306.
responsible for high antimicrobial resistance rates of Poirel L, Revathi G, Bernabeu S & Nordmann P (2011b)
Acinetobacter spp. isolates that cause bacteremia and urinary Detection of NDM-1-producing Klebsiella pneumoniae in
tract infections in Korea. Microb Drug Resist 16: 143–149. Kenya. Antimicrob Agents Ch 55: 934–936.
Pavez M, Mamizuka EM & Lincopan N (2009) Early Pournaras S, Protonotariou E, Voulgari E, Kristo I, Dimitroulia E,
dissemination of KPC-2-producing Klebsiella pneumoniae Vitti D, Tsalidou M, Maniatis AN, Tsakris A & Sofianou D
strains in Brazil. Antimicrob Agents Ch 53: 2702. (2009) Clonal spread of KPC-2 carbapenemase-producing
Peirano G & Pitout JDD (2010) Molecular epidemiology of Klebsiella pneumoniae strains in Greece. J Antimicrob Chemoth
Escherichia coli producing CTX-M b-lactamases: the 64: 348–352.
worldwide emergence of clone ST131 O25:H4. Int J Antimicrob Pournaras S, Poulou A, Voulgari E, Vrioni G, Kristo I & Tsakris A
Ag 35: 316–321. (2010) Detection of the new metallo-b-lactamase VIM-19
Peirano G, Seki LM, Val Passos VL, Pinto MC, Guerra LR & along with KPC-2, CMY-2 and CTX-M-15 in Klebsiella
Asensi MD (2009) Carbapenem-hydrolysing b-lactamase pneumoniae. J Antimicrob Chemoth 65: 1604–1607.
KPC-2 in Klebsiella pneumoniae isolated in Rio de Janeiro, Quinteira S, Grosso F, Ramos H & Peixe L (2007) Molecular
Brazil. J Antimicrob Chemoth 63: 265–268. epidemiology of imipenem-resistant Acinetobacter
Pellegrino FLPC, Casali N, Nouér SA, Riley LW & Moreira BM haemolyticus and Acinetobacter baumannii isolates carrying
(2008) A carbapenem-susceptible Pseudomonas aeruginosa plasmid-mediated OXA-40 from a Portuguese hospital.
strain carrying the blaSPM gene. Diagn Micr Infec Dis 61: Antimicrob Agents Ch 51: 3465–3466.
214–216. Ratkai C, Peixe LV, Grosso F, Freitas AR, Antunes P, Fodor E,
Petrella S, Ziental-Gelus N, Mayer C, Renard M, Jarlier V & Hajdu E & Nagy E (2010) Successful application of the
Sougakoff W (2008) Genetic and structural insights into the DiversiLab repetitive-sequence-based PCR typing system for


on 12 February 2018
confirmation of the circulation of a multiresistant KPC-2, in Klebsiella pneumoniae isolates. J Antimicrob

Pseudomonas aeruginosa clone in different hospital wards. Chemoth 51: 711–714.
Diagn Microbiol Infect Dis 67: 202–206. Suh JY, Son JS, Chung DR, Peck KR, Ko KS & Song JH (2010)
Robledo IE, Aquino EE, Sante MI, Santana JL, Otero DM, Leon Nonclonal emergence of colistin-resistant Klebsiella
CF & Vazquez GJ (2010) Detection of KPC in Acinetobacter pneumoniae isolates from blood samples in South Korea.
spp. in Puerto Rico. Antimicrob Agents Ch 54: 1354–1357. Antimicrob Agents Ch 54: 560–562.
Rogers BA, Sidjabat HE & Paterson DL (2011) Escherichia coli Suzuki S, Shibata N, Yamane K, Wachino Ji, Ito K & Arakawa Y
O25b-ST131: a pandemic, multiresistant, community- (2009) Change in the prevalence of extended-spectrum-b-
associated strain. J Antimicrob Chemoth 66: 1–14. lactamase-producing Escherichia coli in Japan by clonal spread.
Rooney PJ, O’Leary MC, Loughrey AC, McCalmont M, Smyth B, J Antimicrob Chemoth 63: 72–79.
Donaghy P, Badri M, Woodford N, Karisik E & Livermore DM Tartof SY, Solberg OD, Manges AR & Riley LW (2005) Analysis of
(2009) Nursing homes as a reservoir of extended-spectrum b- a uropathogenic Escherichia coli clonal group by multilocus
lactamase (ESBL)-producing ciprofloxacin-resistant sequence typing. J Clin Microbiol 43: 5860–5864.
Escherichia coli. J Antimicrob Chemoth 64: 635–641. Teh CS, Chua KH & Thong KL (2010) Multiple-locus variable-
Ruiz M, Marti S, Fernandez-Cuenca F, Pascual A & Vila J (2007) number tandem repeat analysis of Vibrio cholerae in
High prevalence of carbapenem-hydrolysing oxacillinases in comparison with pulsed field gel electrophoresis and
epidemiologically related and unrelated Acinetobacter virulotyping. J Biomed Biotechnol 2010: 817190.
baumannii clinical isolates in Spain. Clin Microbiol Infec 13: Thomas CP, Elamin N, Doumith M et al. (2009) Hospital
1192–1198. outbreak of Klebsiella pneumoniae producing OXA-48
Samuelsen O, Buaro L, Toleman MA, Giske CG, Hermansen NO, carbapenemase in the United Kingdom. Proceedings of the 49th
Walsh TR & Sundsfjord A (2009a) The first metallo-b- Interscience Conference on Antimicrobial Agents &
lactamase identified in Norway is associated with a TniC-like Chemotherapy, American Society for Microbiology, San
transposon in a Pseudomonas aeruginosa isolate of sequence Francisco (abstract C2-648).
type 233 imported from Ghana. Antimicrob Agents Ch 53: Tibbetts R, Frye JG, Marschall J, Warren D & Dunne W (2008)
331–332. Detection of KPC-2 in a clinical isolate of Proteus mirabilis and
Samuelsen O, Naseer U, Tofteland S, Skutlaberg DH, Onken A, first reported description of carbapenemase resistance caused
Hjetland R, Sundsfjord A & Giske CG (2009b) Emergence of by a KPC b-lactamase in P. mirabilis. J Clin Microbiol 46:
clonally related Klebsiella pneumoniae isolates of sequence type 3080–3083.
258 producing plasmid-mediated KPC carbapenemase in Toleman MA, Simm AM, Murphy TA, Gales AC, Biedenbach DJ,
Norway and Sweden. J Antimicrob Chemoth 63: 654–658. Jones RN & Walsh TR (2002) Molecular characterization of
Samuelsen O, Toleman MA, Sundsfjord A et al. (2010) Molecular SPM-1, a novel metallo-b-lactamase isolated in Latin America:
epidemiology of metallo-b-lactamase-producing Pseudomonas report from the SENTRY antimicrobial surveillance
aeruginosa isolates from Norway and Sweden shows import of programme. J Antimicrob Chemoth 50: 673–679.
international clones and local clonal expansion. Antimicrob Tomas M, Doumith M, Warner M, Turton JF, Beceiro A, Bou G,
Agents Ch 54: 346–352. Livermore DM & Woodford N (2010) Efflux pumps, OprD
Schwarz S, Silley P, Simjee S, Woodford N, van Duijkeren E, porin, AmpC b-lactamase, and multiresistance in
Johnson AP & Gaastra W (2010) Editorial: assessing the Pseudomonas aeruginosa isolates from cystic fibrosis patients.
antimicrobial susceptibility of bacteria obtained from animals. Antimicrob Agents Ch 54: 2219–2224.
J Antimicrob Chemoth 65: 601–604. Toth A, Damjanova I, Puskas E, Janvari L, Farkas M, Dobak A,
Scott FW & Pitt TL (2004) Identification and characterization of Borocz K & Paszti J (2010) Emergence of a colistin-resistant
transmissible Pseudomonas aeruginosa strains in cystic fibrosis KPC-2-producing Klebsiella pneumoniae ST258 clone in
patients in England and Wales. J Med Microbiol 53: 609–615. Hungary. Eur J Clin Microbiol 29: 765–769.
Shevchenko OV & Edelstein MV (2007) Epidemic population Tsakris A, Ikonomidis A, Pournaras S, Tzouvelekis LS, Sofianou
structure of MBL-producing Pseudomonas aeruginosa in D, Legakis NJ & Maniatis AN (2006) VIM-1 metallo-b-
Russia. Program and Abstracts of the 47th Interscience lactamase in Acinetobacter baumannii. Emerg Infect Dis 12:
Conference on Antimicrobial Agents & Chemotherapy. 981–983.
Smet A, Martel A, Persoons D et al. (2010) Characterization of Tsakris A, Ikonomidis A, Poulou A, Spanakis N, Pournaras S &
extended-spectrum b-lactamases produced by Escherichia coli Markou F (2007a) Transmission in the community of clonal
isolated from hospitalized and nonhospitalized patients: Proteus mirabilis carrying VIM-1 metallo-b-lactamase.
emergence of CTX-M-15-producing strains causing urinary J Antimicrob Chemoth 60: 136–139.
tract infections. Microb Drug Resist 16: 129–134. Tsakris A, Ikonomidis A, Spanakis N, Poulou A & Pournaras S
Smith Moland E, Hanson ND, Herrera VL, Black JA, Lockhart TJ, (2007b) Characterization of In3Mor, a new integron carrying
Hossain A, Johnson JA, Goering RV & Thomson KS (2003) VIM-1 metallo-b-lactamase and sat1 gene, from Morganella
Plasmid-mediated, carbapenem-hydrolysing b-lactamase, morganii. J Antimicrob Chemoth 59: 739–741.

c 2011 Federation of European Microbiological Societies

on 12 February 2018
Tsakris A, Ikonomidis A, Poulou A, Spanakis N, Vrizas D, sequence typing of Pseudomonas aeruginosa in cystic fibrosis
Diomidous M, Pournaras S & Markou F (2008a) Clusters of sputum samples. J Clin Microbiol 47: 3444–3448.
imipenem-resistant Acinetobacter baumannii clones producing Wei ZQ, Du XX, Yu YS, Shen P, Chen YG & Li LJ (2007) Plasmid-
different carbapenemases in an intensive care unit. Clin mediated KPC-2 in a Klebsiella pneumoniae isolate from
Microbiol Infec 14: 588–594. China. Antimicrob Agents Ch 51: 763–765.
Tsakris A, Kristo I, Poulou A, Markou F, Ikonomidis A & Wiehlmann L, Wagner G, Cramer N et al. (2007) Population
Pournaras S (2008b) First occurrence of KPC-2-possessing structure of Pseudomonas aeruginosa. P Natl Acad Sci USA 104:
Klebsiella pneumoniae in a Greek hospital and 8101–8106.
recommendation for detection with boronic acid disc tests. Wirth T, Falush D, Lan R et al. (2006) Sex and virulence in
J Antimicrob Chemoth 62: 1257–1260. Escherichia coli: an evolutionary perspective. Mol Microbiol 60:
Turton JF, Gabriel SN, Valderrey C, Kaufmann ME & Pitt TL 1136–1151.
(2007) Use of sequence-based typing and multiplex PCR to Wolter DJ, Black JA, Lister PD & Hanson ND (2009a) Multiple
identify clonal lineages of outbreak strains of Acinetobacter genotypic changes in hypersusceptible strains of Pseudomonas
baumannii. Clin Microbiol Infec 13: 807–815. aeruginosa isolated from cystic fibrosis patients do not always
Turton JF, Matos J, Kaufmann ME & Pitt TL (2009) Variable correlate with the phenotype. J Antimicrob Chemoth 64:
number tandem repeat loci providing discrimination within 294–300.
widespread genotypes of Acinetobacter baumannii. Eur J Clin Wolter DJ, Khalaf N, Robledo IE, Vazquez GJ, Sante MI, Aquino
Microbiol 28: 499–507. EE, Goering RV & Hanson ND (2009b) Surveillance of
Valverde A, Canton R, Garcillan-Barcia MP, Novais A, Galan JC, carbapenem-resistant Pseudomonas aeruginosa isolates from
Alvarado A, de la Cruz F, Baquero F & Coque TM (2009) Puerto Rican medical center hospitals: dissemination of KPC
Spread of blaCTX-M-14 is driven mainly by IncK plasmids and IMP-18 b-lactamases. Antimicrob Agents Ch 53:
disseminated among Escherichia coli phylogroups A, B1, and D 1660–1664.
in Spain. Antimicrob Agents Ch 53: 5204–5212. Woodford N, Tierno PM Jr, Young K et al. (2004a) Outbreak of
van Belkum A (2007) Tracing isolates of bacterial species by
Klebsiella pneumoniae producing a new carbapenem-
multilocus variable number of tandem repeat analysis
hydrolyzing class A b-lactamase, KPC-3, in a New York
(MLVA). FEMS Immunol Med Mic 49: 22–27.
Medical Center. Antimicrob Agents Ch 48: 4793–4799.
van Belkum A, Tassios PT, Dijkshoorn L et al. (2007) Guidelines
Woodford N, Ward ME, Kaufmann ME et al. (2004b)
for the validation and application of typing methods for use in
Community and hospital spread of Escherichia coli producing
bacterial epidemiology. Clin Microbiol Infec 13: 1–46.
CTX-M extended-spectrum b-lactamases in the UK.
Viedma E, Juan C, Acosta J, Zamorano L, Otero JR, Sanz F,
Chaves F & Oliver A (2009) Nosocomial spread of colistin-
Woodford N, Reddy S, Fagan EJ et al. (2007) Wide geographic
only-sensitive sequence type 235 Pseudomonas aeruginosa
spread of diverse acquired AmpC b-lactamases among
isolates producing the extended-spectrum b-lactamases GES-1
Escherichia coli and Klebsiella spp. in the UK and Ireland.
and GES-5 in Spain. Antimicrob Agents Ch 53: 4930–4933.
Villegas MV, Lolans K, Correa A, Jose Suarez C, Lopez JA, Vallejo
Woodford N, Zhang J, Warner M, Kaufmann ME, Matos J,
M & Quinn JP & the Colombian Nosocomial Resistance Study
MacDonald A, Brudney D, Sompolinsky D, Navon-Venezia S
Group (2006) First detection of the plasmid-mediated class A
carbapenemase KPC-2 in clinical isolates of Klebsiella & Livermore DM (2008) Arrival of Klebsiella pneumoniae
pneumoniae from South America. Antimicrob Agents Ch 50: producing KPC carbapenemase in the United Kingdom.
2880–2882. J Antimicrob Chemoth 62: 1261–1264.
Villegas MV, Lolans K, Correa A, Kattan JN, Lopez JA & Quinn JP Woodford N, Carattoli A, Karisik E, Underwood A, Ellington MJ
& and the Colombian Nosocomial Resistance Study Group & Livermore DM (2009) Complete nucleotide sequences of
(2007) First identification of Pseudomonas aeruginosa isolates plasmids pEK204, pEK499, and pEK516, encoding CTX-M
producing a KPC-type carbapenem-hydrolyzing b-lactamase. enzymes in three major Escherichia coli lineages from the
Antimicrob Agents Ch 51: 1553–1555. United Kingdom, all belonging to the international O25:H4-
Vincent C, Boerlin P, Daignault D et al. (2010) Food reservoir for ST131 clone. Antimicrob Agents Ch 53: 4472–4482.
Escherichia coli causing urinary tract infections. Emerg Infect Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A,
Dis 16: 88–95. Biddle JW, Steward CD, Alberti S, Bush K & Tenover FC (2001)
Vu-Thien H, Corbineau G, Hormigos K, Fauroux B, Corvol H, Novel carbapenem-hydrolyzing b-lactamase, KPC-1, from a
Clement A, Vergnaud G & Pourcel C (2007) Multiple-locus carbapenem-resistant strain of Klebsiella pneumoniae.
variable-number tandem-repeat analysis for longitudinal Antimicrob Agents Ch 45: 1151–1161.
survey of sources of Pseudomonas aeruginosa infection in cystic Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K &
fibrosis patients. J Clin Microbiol 45: 3175–3183. Walsh TR (2009) Characterization of a new metallo-b-
Waine DJ, Honeybourne D, Smith EG, Whitehouse JL & Dowson lactamase gene, blaNDM-1, and a novel erythromycin esterase
CG (2009) Cross-sectional and longitudinal multilocus gene carried on a unique genetic structure in Klebsiella


on 12 February 2018
pneumoniae sequence type 14 from India. Antimicrob Agents Clinical Microbiology and Infectious Diseases, ESCMID,
Ch 53: 5046–5054. Helsinki (abstract P1696).
Zarkotou O, Pournaras S, Voulgari E, Chrysos G, Prekates A, Zhang R, Zhou HW, Cai JC & Chen GX (2007) Plasmid-mediated
Voutsinas D, Themeli-Digalaki K & Tsakris A (2010) Risk carbapenem-hydrolysing b-lactamase KPC-2 in carbapenem-
factors and outcomes associated with acquisition of colistin- resistant Serratia marcescens isolates from Hangzhou, China.
resistant KPC-producing Klebsiella pneumoniae: a matched J Antimicrob Chemoth 59: 574–576.
case-control study. J Clin Microbiol 48: 2271–2274. Zhang R, Yang L, Cai JC, Zhou HW & Chen GX (2008) High-level
Zarrilli R, Giannouli M, Tomasone F, Triassi M & Tsakris A carbapenem resistance in a Citrobacter freundii clinical isolate
is due to a combination of KPC-2 production and decreased
(2009) Carbapenem resistance in Acinetobacter baumannii: the
porin expression. J Med Microbiol 57: 332–337.
molecular epidemic features of an emerging problem in health
Zhang W, Qi W, Albert TJ, Motiwala AS, Alland D, Hyytia-Trees
care facilities. J Infect Dev Ctries 3: 335–341.
EK, Ribot EM, Fields PI, Whittam TS & Swaminathan B
Zavascki AP, Gaspareto PB, Martins AF, Goncalves AL & Barth
(2006) Probing genomic diversity and evolution of Escherichia
AL (2005) Outbreak of carbapenem-resistant Pseudomonas coli O157 by single nucleotide polymorphisms. Genome Res 16:
aeruginosa producing SPM-1 metallo-b-lactamase in a 757–767.
teaching hospital in southern Brazil. J Antimicrob Chemoth 56: Zioga A, Miriagou V, Tzelepi E, Douzinas E, Tsakiri M, Legakis
1148–1151. NJ, Daikos GL & Tzouvelekis LS (2010) The ongoing challenge
Zhang J, Pike R, Maharjan S et al. (2009) OXA-48 of acquired carbapenemases: a hospital outbreak of Klebsiella
carbapenemase-producing Klebsiella pneumoniae in the UK. pneumoniae simultaneously producing VIM-1 and KPC-2. Int
Proceedings and Abstracts of the 19th European Congress of J Antimicrob Ag 36: 190–191.


on 12 February 2018

(2011) - Multiresistant Gram-Negative Bacteria - The Role of High-Risk Clones in The Dissemination of Antibiotic Resistance. Woodford Et. Al

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Multiresistant Gram-negative bacteria: the role of high-risk clones

Correspondence: Neil Woodford, Abstract

understood survival traits – and a flexible ability to accumulate and switch

no-cephalosporins in addition to other drug classes, but will

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Fig. 1. ‘Population Snapshot’ determined by

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Fig. 3. eBURST analysis (http://eburst.mlst.net) to

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confirmation of the circulation of a multiresistant KPC-2, in Klebsiella pneumoniae isolates. J Antimicrob

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