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. 2016 Feb 26;60(3):1912–1917. doi: 10.1128/AAC.02756-15

KPC-Like Carbapenemase-Producing Enterobacteriaceae Colonizing Patients in Europe and Israel

A Baraniak a, R Izdebski a, J Fiett a, M Herda a, L P G Derde b, M J M Bonten b, A Adler c, Y Carmeli c, H Goossens d, W Hryniewicz a, C Brun-Buisson e, M Gniadkowski a,✉, on behalf of the MOSAR WP2, WP3, and WP5 Study Groups
PMCID: PMC4775924  PMID: 26711772

Abstract

In a 2008-2011 survey, 17,945 patients in 18 hospital units in Europe and Israel were screened for carriage of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae, resulting in identification of 124 positive patients. The isolates were dominated by Klebsiella pneumoniae sequence type 258 (ST258) KPC-2 and ST512 KPC-3, mainly from Greece and Italy, respectively, whereas Israeli isolates were of diverse species, clones, and KPC variants. Various blaKPC platforms were observed, among which IncFIIK-FIBK plasmids with blaKPC-2/-3 genes in the Tn4401a transposon prevailed.

TEXT

Carbapenemase-producing Enterobacteriaceae (CPE) constitute an urgent epidemiological issue (1). One of their major, globally spread mechanisms is Klebsiella pneumoniae carbapenemases (KPCs), which hydrolyze most β-lactams (1, 2). KPC-2 and -3 are the most prevalent variants, while K. pneumoniae is their predominant host species (3, 4). KPCs have occurred in many K. pneumoniae clones (sequence types [STs]) (5–8), but ST258 and its close relative ST512 are key players in the pandemic spread (2–4, 6, 9–11). blaKPC genes are located in Tn4401 transposon variants (12–15) and inserted into plasmids of various replicon types and transmission potentials (5, 7, 16–20). One type of these, pKpQIL, found first in KPC-3-producing K. pneumoniae ST258 in Israel, has two specific replicons, FIIK and FIBK, and low conjugation efficiency (21–23). Later, KPC-2- or -3-encoding pKpQIL-like molecules were observed in other countries, usually in K. pneumoniae ST258 (2, 3, 10, 24, 25).

During the European Union project MOSAR (Mastering hOSpital Antimicrobial Resistance in Europe), patients in intensive care units (ICUs) and rehabilitation units (RUs) in Europe and Israel were screened for Enterobacteriaceae resistant to expanded-spectrum cephalosporins (ESCs) (26). Since KPCs and metallo-β-lactamases (MBLs) confer resistance to ESCs (1), the project allowed performance of a large-scale comparative study of the KPC and MBL CPE carriage. A previous report concerned MBL CPE (27), while here we present the KPC data.

Between mid-2008 and mid-2011, all patients in 13 ICUs and five RUs in nine countries (n = 17,945) were screened for ESC-resistant (ESC-R) Enterobacteriaceae (Table 1). Rectal swabbing was performed regularly from admission until discharge. Swabs were plated onto Brilliance ESBL agar (Oxoid, Basingstoke, United Kingdom); enterobacterial colonies were stored for definite analysis. Species were identified with Vitek 2 (bioMérieux, Marcy l'Etoile, France). All isolates were tested for extended-spectrum β-lactamases (ESBLs) and AmpC-type cephalosporinases by the ESBL double-disk synergy test (DDST) without and with 250 μg/ml cloxacillin (28) and for susceptibility to ertapenem, imipenem, and meropenem. Carbapenemase screening breakpoints were from EUCAST (http://eucast.org). All suspected CPE isolates were subjected to KPC, MBL, and OXA-48 phenotypic detection, using the combined disk test with phenylboronic acid (PBA CDT) (29), the DDST with EDTA (30), and the temocillin disk (31), respectively. All nonduplicate PBA CDT-positive organisms were tested by PCR for blaKPC genes (32), and this test was performed also for putative MBL producers (27).

TABLE 1.

Occurrence of patients colonized by KPC CPE in study centers

Country Center Unit type No. of patients enrolled in the studya No. (%) of patients colonized by Enterobacteriaceae producing acquired ESC-hydrolyzing β-lactamasesb,c,d No. (%) of patients colonized by CPEb,d,e No. (%) of patients colonized by KPC CPEd
France HM ICU 2,373 256 (10.8) 1 (0.04)e
France RP ICU 1,328 85 (6.4) 1 (0.08)f 1 (0.08)
France SJ ICU 1,049 51 (4.9) 4 (0.4)
Greece AT ICU 796 117 (14.7) 53 (6.7)g 44 (5.5)
Greece LA ICU 558 99 (17.7) 83 (14.9)h 35 (6.3)
Italy CA ICU 788 49 (6.2) 2 (0.3)
Latvia RI ICU 1,464 526 (35.9) 10 (0.7)
Luxemburg LU ICU 1,823 54 (3.0)
Portugal PO ICU 910 18 (2.0)
Portugal VR ICU 628 24 (3.8) 1 (0.2)
Slovenia GO ICU 919 32 (3.5)
Slovenia LJ ICU 685 115 (16.8)
Spain BA ICU 1,069 41 (3.8)
France BM RU 410 76 (18.5)
Israel LH RU 564 177 (31.4) 6 (1.1)i 6 (1.1)
Israel TA RU 1,650 870 (52.7) 16 (1.0)j 16 (1.0)
Italy FS RU 704 340 (48.3) 28 (4.0) 22 (2.8)
Spain GI RU 227 104 (45.8) 5 (2.2)
Total 17,945 3,034 (16.9) 210 (1.2) 124 (0.7)
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a

All patients that were swabbed at least once at a clinical center, regardless of the length of hospitalization.

b

These numbers were shown also in the report on colonization by MBL CPE in MOSAR centers (27).

c

Acquired ESC-hydrolyzing β-lactamases include ESBLs, AmpC-type cephalosporinases, MBLs, and KPCs.

d

Patients in this column include both those who were colonized at admission and those who were colonized due to in-hospital transmission.

e

Carbapenemases include KPCs and MBLs except in one patient in the French ICU HM who was colonized with E. coli coproducing OXA-48 carbapenemase and ESBL.

f

This patient was colonized by KPC-producing K. pneumoniae and MBL-producing E. coli.

g

One patient was colonized by KPC-producing E. coli and MBL-producing K. pneumoniae.

h

Four patients were colonized by K. pneumoniae coproducing KPC and MBL.

i

One patient was colonized by KPC-producing E. coli and K. pneumoniae.

j

Two patients were colonized by two different KPC producers: either C. freundii and E. coli or E. coli and K. pneumoniae.

A total of 124 patients carrying 127 unique KPC CPE organisms were identified in 6 of 18 clinical sites, located in Greece (centers AT, n = 44, and LA, n = 35), France (center RP, n = 1), Israel (center LH, n = 6, and TA, n = 16), and Italy (center FS, n = 22) (Table 1). They were 59.0% of all patients with CPE. Four Greek patients had K. pneumoniae strains coproducing KPC and MBL (VIM-1) and were reported previously too (27). The results for individual countries concurred with those of other reports. Since 2008, after the nationwide outbreak in 2006 and 2007, KPCs in Israel have been endemic at a lower level (2, 33, 34). Consistently, the KPC cases in the Israeli RUs were scattered during the study, being ∼1% of all patients screened and ∼2% of those with ESC-R organisms (Table 1). The KPC spread in Greece commenced in 2007 and was much advanced by mid-2008 (2, 34–36). Both Greek ICUs recorded KPC cases from the survey start, and their contribution to all patients screened and to ESC-R Enterobacteriaceae carriers was ∼6% and ∼35%, respectively. Italy reported the first KPC case in 2008, followed by an outbreak progressing rapidly from 2010 (2, 34, 37). The RU FS, screening patients from February 2009 to February 2011, had its first 2 cases late in 2009 and then 12 in 2010 and 8 in the first 2 months of 2011, being ∼3% of all patients and ∼6% of those with ESC-R organisms.

The blaKPC amplicons were digested by RsaI (Fermentas, Vilnius, Lithuania), which distinguishes blaKPC-2 and blaKPC-3 (38), followed by sequencing for representative isolates. KPC-producing isolates were typed by pulsed-field gel electrophoresis (PFGE) as described previously (39). PFGE types and subtypes were distinguished visually according to the method of Tenover et al. (40). Selected isolates were analyzed also by multilocus sequence typing (MLST) (41–44); databases available at http://pubmlst.org/cfreundii/ (Citrobacter freundii), http://pubmlst.org/ecloacae (Enterobacter cloacae), http://mlst.warwick.ac.uk/mlst/dbs/Ecoli (Escherichia coli), and http://bigsdb.web.pasteur.fr/klebsiella/klebsiella.html (K. pneumoniae) were used for assigning STs. E. cloacae STs and β-lactamases were shown previously (45).

K. pneumoniae isolates, being the predominant species (n = 110; 86.6%), were classified into 10 STs (Table 2). ST258 prevailed (n = 76; 69.1%) and was observed in all but one of the sites (FS, Italy), dominating in Greece with blaKPC-2 (n = 73; 93.6%). The next-most-prevalent clone, ST512 (n = 21; 19.1%), was originally identified in this study in an Israeli isolate from 2008 (http://bigsdb.web.pasteur.fr/klebsiella/klebsiella.html). This single-locus variant (SLV) of ST258 carried blaKPC-3 and dominated in the Italian RU FS (n = 19; 86.4%) but was sporadic in Israel. Four KPC-2- and VIM-1-positive Greek isolates belonged to ST147, the major VIM producer in Greece (27), while the remaining STs represented single isolates with KPC-2 or -3 in individual sites. C. freundii, E. cloacae, and E. coli, usually producing KPC-2s, were identified vastly in Israel and were clonally diverse, except for E. coli ST131, of which there were three KPC-2 or -3 isolates. Most of the E. cloacae, E. coli, and K. pneumoniae isolates represented international clones (45, 46). For C. freundii, the clonality data are scarce (27, 41, 47), but KPC-producing C. freundii ST14, originally identified in this study, was found in 2015 in Malaysia [http://pubmlst.org/cfreundii/]. In general, the clonality plus KPC type data were congruent with data in national reports. The high KPC CPE diversity in the Israeli centers corresponds to the endemicity situation following the polyclonal outbreak of KPC-2 and the clonal spread of K. pneumoniae ST258 KPC-3 (7, 19, 22, 48, 49), even if other studies still indicate the importance of K. pneumoniae ST258/ST512 (50). In contrast, the high prevalence of ST258 KPC-2 in Greece and ST512 KPC-3 in Italy reflected their clonal dissemination in real time (35–37). This study is also yet another report on KPC-producing E. coli ST131, which has been repeatedly identified in Israel (4, 49, 51, 52).

TABLE 2.

Geographic distribution, species, clones, pulsotypes, S1 plasmid profiles, plasmids and Tn4401 transposons with blaKPC genes, and other acquired β-lactamases of KPC CPE isolatesa

Center Species ST (CC or CG)b No. of isolates No. of pulsotypes (no. of subtypes) S1 profilec Size of plasmid (kb); replicon(s) of plasmid with blaKPC gene(s)d blaKPCe Tn4401 variantf MBL, ESBL, and/or AmpC (no. of isolates)g
AT (Greece) E. coli ST10 (CC10) 1 1 Eco1 ∼130; FIIK + FIBK blaKPC-2 Tn4401a TEM-1
K. pneumoniae ST258 (CG258) 43 2 (18) Kpn1 ∼120; FIIK + FIBK blaKPC-2 Tn4401a SHV-12 + TEM-1
Kpn2 ∼115; FIIK + FIBK blaKPC-2 Tn4401a SHV-12 + TEM-1
LA (Greece) K. pneumoniae ST17 (CG17) 1 1 Kpn4 ∼115; FIIK + FIBK blaKPC-2 Tn4401a SHV-5 + TEM-1
K. pneumoniae ST147 (CC147)h 4 1 (2) Kpn6 ∼115; FIIK + FIBK blaKPC-2 Tn4401a VIM-1 + TEM-1
Kpn9 ∼100; FIIK + FIBK
K. pneumoniae ST258 (CG258) 30 1 (12) Kpn2 ∼115; FIIK + FIBK blaKPC-2 Tn4401a SHV-12 + TEM-1
Kpn10 ∼70; NT blaKPC-2 Tn4401a SHV-12
FS (Italy) K. pneumoniae ST16 (CG17) 1 1 Kpn7 ∼90; NT blaKPC-3 Tn4401a CTX-M-15
K. pneumoniae ST45 (CG485) 1 1 Kpn3 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1
K. pneumoniae ST383 (CC42) 1 1 Kpn8 ∼100; FIIK blaKPC-2 Tn4401a CMY-4 + TEM-1
K. pneumoniae ST512 (CG258) 19 1 (9) Kpn2/6 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1 (19); SHV-12 + CMY-2 (1); OXA-1 (1)i
RP (France) K. pneumoniae ST258 (CG258) 1 1 ND ND blaKPC-2 Tn4401a CTX-M-15 + SHV + TEM-1
LH (Israel) E. cloacae ST78 (CC74)j 1 1 Ecl1 ND blaKPC-2 Tn4401c SHV-12 + TEM-1j
E. coli ST131 (CC131) 2 1 (2) Eco2 ∼75; N blaKPC-2 Tn4401g TEM-1
E. coli ST167 (CC10) 1 1 Eco4 ∼90; FIIK + FIBK blaKPC-3 Tn4401a SHV-12 + TEM-1
E. coli ST1571 1 1 Eco3 ND blaKPC-2 Tn4401c SHV-12 + TEM-1
K. pneumoniae ST258 (CG258) 1 1 Kpn5 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1
K. pneumoniae ST512 (CG258) 1 1 Kpn11 ∼150; N blaKPC-3 Tn4401a -
TA (Israel) C. freundii ST14 1 1 Cfr1 ∼80; N blaKPC-2 Tn4401g TEM-1 + OXA-1
C. freundii ST12 1 1 Cfr2 ∼80; N blaKPC-2 Tn4401g CTX-M-15 + TEM-1
C. freundii ND 1 1 Cfr3 ∼80; N blaKPC-2 Tn4401g SHV-12 + TEM-1 + OXA-1
C. freundii ST10 1 1 Cfr4 ∼300; ND blaKPC-2 Tn4401c TEM-1 + OXA-1
C. freundii ST15 1 1 Cfr4 ∼300; ND blaKPC-2 Tn4401c TEM-1 + OXA-1
E. cloacae ST118j 1 1 Ecl3 ∼320; ND blaKPC-2 Tn4401c CTX-M-27 + SHV-12 + TEM-1j
E. cloacae ST146j 1 1 Ecl2 ∼300; ND blaKPC-2 Tn4401c TEM-1j
E. coli ST69 (CC69) 1 1 Eco8 ∼70; N blaKPC-2 NT TEM-1
E. coli ST131 (CC131) 1 1 Eco5 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1
E. coli ST216 1 1 Eco6 ∼60; N blaKPC-2 Tn4401g TEM-1 + OXA-1
E. coli ST3541 1 1 Eco7 ND blaKPC-2 Tn4401c CTX-M-15 + SHV-12 + CMY-2 + TEM-1 + OXA-1
K. pneumoniae ST17 (CG17) 1 1 Kpn12 ∼140; N blaKPC-2 Tn4401g TEM-1 + OXA-1
K. pneumoniae ST34 (CC34) 1 1 Kpn13 ND blaKPC-2 Tn4401c CTX-M-15 + SHV-12 + TEM-1 + OXA-1
K. pneumoniae ST36 (CG485) 1 1 Kpn14 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1
K. pneumoniae ST258 (CG258) 1 1 Kpn2 ∼115; FIIK + FIBK blaKPC-3 Tn4401a TEM-1
K. pneumoniae ST383 (CC42) 1 1 Kpn15 ∼115; FIBK blaKPC-2 Tn4401a CTX-M-15 + CMY-4 + TEM-1
K. pneumoniae ST512 (CG258) 1 1 Kpn16 ∼140; FIIK + FIBK blaKPC-3 Tn4401a TEM-1 + OXA-1
K. pneumoniae ST833 (CG258) 1 1 Kpn17 ∼100; FIIK + FIBK blaKPC-2 Tn4401a SHV-12
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a

Other acquired β-lactamases include MBLs, ESBLs, AmpCs, and broad-spectrum β-lactamases. CC, clonal complex; CG, clonal group; ND, not determined; NT, nontypeable; FIIK, FIBK, and N are plasmid replicon types.

b

New STs are indicated in bold. Numerous reports on K. pneumoniae ST512 have been published since 2012 (2, 11, 34, 37); however, this ST was identified originally in this study (isolate identifier 578 in the K. pneumoniae MLST database [http://bigsdb.web.pasteur.fr]). In groups of four or more isolates, MLST was performed for representative isolates, based on the PFGE data.

c

In large groups of isolates of the same ST/pulsotype (K. pneumoniae ST258 and ST512), the S1 analysis was performed for representative isolates. S1 plasmid profiles are numbered within species groups of isolates; profiles differed from each other by number and/or size of plasmids.

d

Plasmids found in transformants are shown in bold. Replicons shown in italics represent the probable types of blaKPC plasmids (PBRT and pKpQIL PCR mapping was performed on DNA of clinical isolates).

e

In groups of four or more isolates of the same ST/pulsotype, blaKPC sequencing was performed for representative isolates; for the remaining isolates, RsaI PCR-restriction fragment length polymorphism analysis distinguishing blaKPC-2 and blaKPC-3 sequences (38) was carried out.

f

In groups of four or more isolates of the same ST/pulsotype, PCR mapping of Tn4401-like elements was performed for representative isolates.

g

In groups of four or more isolates with the same ST/pulsotype and bla genes, PCR profile sequencing was performed for representative isolates.

h

These isolates were also included in the study of MBL CPE isolates identified during the MOSAR project (27).

i

All isolates of this group produced TEM-1; one isolate produced additionally SHV-12 and CMY-2, and another one produced OXA-1.

j

STs and β-lactamases of the E. cloacae isolates from LH and TA were reported previously (45).

The location of blaKPC genes within Tn4401-like transposons and polymorphism of these was analyzed by PCR mapping (12). For the Tn4401g variant (15), an additional primer was designed (5′-GTTCCACTGAGCGTCAGAC-3′) for use with primer 3781L (12) (expected product size, 370 bp). All blaKPC genes were located in Tn4401 variants (12). The main type was Tn4401a (12), observed in all isolates from Greece, Italy, and France and in 9/22 Israeli isolates, including most K. pneumoniae isolates with blaKPC-2 or blaKPC-3 (Table 2). Tn4401c (14) and Tn4401g (15) were found only in Israel in various species and clones, always containing blaKPC-2. Tn4401a has been the main type of Tn4401, strongly associated with K. pneumoniae ST258 worldwide (6, 10, 18, 21, 36), while Tn4401c has been observed in diverse KPC-2-producing organisms in Israel (15, 49). Interestingly, Tn4401c-derived Tn4401g was identified only recently in a single K. pneumoniae KPC-2 isolate recovered in Israel in 2008 (15), whereas in this study, it occurred frequently in C. freundii, E. coli, and K. pneumoniae.

Plasmid profiling and identification of blaKPC-carrying plasmids was done with nuclease S1 (New England BioLabs, Beverly, MA) analysis (53) and hybridization with the blaKPC probe, using the enhanced-chemiluminescence (ECL) Random-Prime labeling and detection system (Amersham Pharmacia Biotech, Little Chalfont, United Kingdom). The analysis comprised 44 isolates of all species, STs, and pulsotypes (15 K. pneumoniae ST258/ST512 isolates), revealing highly varied plasmid profiles, with blaKPC-carrying plasmids ranging in size from ∼60 to ∼320 kb (Table 2). Plasmid DNA of 27 isolates of various species, STs, and S1 profiles was purified with the Qiagen plasmid midi kit (Qiagen, Hilden, Germany) and electroporated into E. coli DH5α, with transformant selection with 0.5 μg/ml imipenem or 1 μg/ml cefotaxime. Subsequently, plasmids of the transformants were purified and subjected to PCR-based replicon typing (PBRT) (54–57). KPC-positive transformants were obtained for 22 isolates (Table 2). PBRT revealed that 12 of these had plasmids with FIIK and FIBK replicons (alternating in two cases) of ∼90 to ∼140 kb. PCR mapping, performed as proposed by Baraniak et al. (10), showed that all these were of the pKpQIL type (21), and molecules positive in that assay were identified also in selected isolates for which no transformants were available (Table 2). The pKpQIL-like plasmids carried blaKPC-2 or blaKPC-3 (Tn4401a) and were hosted mainly in K. pneumoniae ST258 and ST512 isolates; however, these occurred also in other organisms (10, 22, 23). The other group was IncN plasmids of ∼60 to ∼150 kb, identified in various C. freundii, E. coli, and K. pneumoniae Israeli strains, usually carrying blaKPC-2 (Tn4401g). These plasmids have been observed among diverse KPC-2-producing E. coli and non-CG258 K. pneumoniae isolates in Israel (15, 49). However, some of our isolates fell beyond this pattern, like K. pneumoniae ST833 (SLV of ST258), with blaKPC-2 on a pKpQIL-like plasmid or K. pneumoniae ST512 with blaKPC-3 on an IncN molecule. Finally, the blaKPC-2 gene in the Tn4401c variant was observed in C. freundii and E. cloacae in large plasmids (∼300 to ∼320 kb) that could not be separated by transfer despite repeated attempts; their replicon types thus remained undetermined.

The KPC CPE isolates were analyzed for other acquired β-lactamase genes, namely, blaSHV-5/SHV-12, blaCTX-M, blaCMY-2, blaTEM, and blaOXA-1 types, by PCR and sequencing (32, 58–60). The isolates had various β-lactamase combinations, including SHV- and CTX-M-like ESBLs, AmpCs of the CMY-2 type, and broad-spectrum TEM-1 and OXA-1 enzymes (Table 2).

We assessed the KPC CPE carriage among ICU and RU patients on a large international scale, using the same time frame and methodology. Not surprisingly, KPC producers were found mainly in the countries which reported their wide spread, i.e., Greece, Italy, and Israel (2, 33–37). Considering the study period, 2008 to 2011, the rhythm of occurrence of cases in individual centers and characteristics of the organisms reflected the situation in the countries, i.e., the onset and advanced stage of nationwide outbreaks in Italy and Greece, respectively, and the postoutbreak endemicity in Israel (33, 35–37). The analysis provided a comparative snapshot of the geographic and quantitative distribution of species/clones, Tn4401 transposon variants, and blaKPC-carrying plasmids, often observed in national reports. Also, this has been one of the first studies of C. freundii and E. cloacae that included MLST data.

ACKNOWLEDGMENTS

The MOSAR WP2, WP3, and WP5 Study Groups also included the following: M. J. Dautzenberg, University Medical Center Utrecht, Utrecht, The Netherlands; M. Kazma and S. Navon-Venezia, Division of Epidemiology and Preventive Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; S. Malhotra-Kumar and C. Lammens, University of Antwerp, Antwerp, Belgium; P. Legrand, Hopital Henri Mondor, Créteil, France; D. Annane, Hôpital Raymond Poincaré, Garches, France; A. Chalfine, Groupe Hospitalier Paris, Saint Joseph, Paris, France; H. Giamarellou, Attikon General Hospital, Athens, Greece; G. L. Petrikkos, Laikon General Hospital, University of Athens, Athens, Greece; G. Nardi, Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy; A. Balode and U. Dumpis, Paul Stradins University Hospital, Riga, Latvia; P. Stammet, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg; I. Aragăo, Central Hospital of Porto, Porto, Portugal; F. Esteves, Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal; I. Muzlovic, University Medical Centre Ljubljana, Ljubljana, Slovenia; V. Tomic, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; A. Torres Martí, Hospital Clínic, University of Barcelona, Barcelona, Spain; C. Lawrence, Hôpital Maritime de Berck, Berck, France, and Garches, Paris, France; J. Salomon, INSERM, Institut Pasteur, Cnam, Paris, France; M. Paul, Loewenstein Hospital, Ra'anana, Israel; Y. Lerman, Geriatric Division, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; A. Rossini and A. Salvia, Fondazione Santa Lucia IRCCS, Rome, Italy; and J. Vidal Samso and J. Fierro, Institute Guttmann, Barcelona, Spain.

We thank curator teams of the Medical University in Białystok, Poland, the National Center for Global Health and Medicine in Tokyo, Japan, the University of Warwick in Warwick, United Kingdom, and the Institut Pasteur in Paris, France, for curating the MLST data of C. freundii, E. cloacae, E. coli, and K. pneumoniae, respectively, and making them publicly available.

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