# Highly drug-resistant Salmonella enterica serotype Kentucky ST198-X1: a microbiological study

Simon Le Hello, Dorothée Harrois, Brahim Bouchrif, Lucile Sontag, Dalèle Elhani, Véronique Guibert, Khalid Zerouali, François-Xavier Weill

► To cite this version:

Simon Le Hello, Dorothée Harrois, Brahim Bouchrif, Lucile Sontag, Dalèle Elhani, et al. Highly drug-resistant Salmonella enterica serotype Kentucky ST198-X1: a microbiological study. The Lancet Infectious Diseases, 2013, 13 (8), pp.672-679. 10.1016/S1473-3099(13)70124-5. pasteur-01109890

HAL Id: pasteur-01109890

https://pasteur.hal.science/pasteur-01109890

Submitted on 12 Mar 2019

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
27 SUMMARY (253)

28 Background

29 *Salmonella* is a major food-borne pathogen found worldwide, which can cause life-
30 threatening infections. Ciprofloxacin and extended-spectrum cephalosporins (ESCs) are the
31 drugs of choice for severe *Salmonella* infections. We previously reported a ciprofloxacin-
32 resistant *S. enterica* serotype Kentucky strain (*Salmonella* Kentucky ST198-X1 CIP<sup>R</sup>) that
33 emerged in Egypt and spread throughout Africa and the Middle East from 2002 to 2008.
34

35

35 Methods

36 Data for *Salmonella* Kentucky collected by the French national *Salmonella* laboratory
37 surveillance system from 2000 to 2011 and by two sites in Casablanca, Morocco, from 2003
38 to 2011 were analysed. Isolates displaying resistance to ESCs and/or with decreased
39 susceptibility to carbapenems were studied by XbaI pulsed-field gel electrophoresis and by
40 multilocus sequence typing. The mechanisms of resistance to antimicrobial drugs were
41 identified.
42

42

43 Findings

44 Isolations of *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup> have recently increased in frequency (376
45 isolates for 2009-2011 versus 200 for 2000-2008) in France, and the geographic area in which
46 infections occur has expanded to include the Indian subcontinent and South-East Asia. We
47 have observed multiple acquisitions of extended-spectrum β-lactamase (CTX-M-1, CTX-M-
48 15), plasmid-encoded cephalosporinase (CMY-2), or carbapenemase (OXA-48, VIM-2) genes
49 by *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup> isolates from the Mediterranean area since 2009.
50 Many of these highly drug-resistant *Salmonella* isolates are also resistant to most
51 aminoglycosides (*armA* gene) and to azithromycin (*mph(A)* gene).
## Panel: Research in context

53

## Systematic review

We searched PubMed for articles published up to January 30, 2013, with the search terms "Salmonella" and "carbapenemases" or "carbapenems" or "NDM-1". No language restrictions were used. We identified only five studies describing various sporadic *Salmonella* spp. isolates resistant to carbapenems. None of these isolates was also resistant to fluoroquinolones. Two of these studies concerned isolates resistant to carbapenems due to mechanisms other than carbapenemase production: two clinical isolates of serotype Wien, which had lost a porin and produced cephapycinase CMY-4, in Tunisia in 2001, and one clinical isolate of serotype Typhimurium, which had lost two porins and produced cephapycinase CMY-2, in Taiwan in 2010.²⁰,²¹ The first carbapenemase producer was a clinical isolate of serotype Cubana, which produced carbapenemase KPC-2 and was obtained in the US in 1998.²²,²³ In 2011 and 2012, the first two clinical isolates of NDM-1-producing *Salmonella* of serotypes Senftenberg and Westhampton were reported, isolated from patients returning from India.²⁴,²⁵ In 2012, the first carbapenemase (VIM-1)-producing *S. enterica* isolates were isolated from food animals in Europe.²⁶

69

## Interpretation

This report confirms the emergence of highly drug-resistant *Salmonella* Kentucky, a potential risk to Public Health, in the Mediterranean basin. This ciprofloxacin-resistant *Salmonella* Kentucky ST198-X1 strain, which is increasingly frequently isolated, has recently acquired β-lactamases (CTX-M ESBLs, CMY-2 AmpC, and VIM-2 and OXA-48 carbapenemases) encoding resistance to extended-spectrum cephalosporins and carbapenems. Further efforts are required from national and international health, food and agricultural authorities, to
77 control the spread of this highly drug-resistant strain in humans and food animals. We

78 propose the inclusion of ciprofloxacin-resistant *Salmonella* Kentucky as a new target strain, in

79 national programmes for the control of *Salmonella* in poultry.

80

81 **Funding**

82 Institut Pasteur, Institut de Veille Sanitaire, “Fondation pour la Recherche Médicale” (DH),

83 the French Government “Investissement d'Avenir” programme.

84

85
86

**Box**

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109
110 INTRODUCTION

111 Antimicrobial drug-resistant bacteria are a serious challenge for the clinical care of patients
112 and for Public Health in the 21st century.¹ The Gram-negative “superbugs”, such as those
113 resistant to extended-spectrum cephalosporins (ESCs) due to the production of either
114 extended-spectrum β-lactamases (ESBLs) or cephamycinases (AmpC), seem to have now
115 eclipsed Gram-positive “superbugs” (i.e., methicillin-resistant *Staphylococcus aureus* and
116 vancomycin-resistant *Enterococcus* spp). Furthermore, the recent emergence of
117 Enterobacteriaeceae resistant to all β-lactam antibiotics, including ESCs and carbapenems, is
118 of particular concern, because carbapenems are, in many cases the last option available for
119 treating serious infection with ESC-resistant Gram-negative bacteria. Indeed, the development
120 pipeline for new antimicrobial drugs with bactericidal activity against Gram-negative bacteria
121 has now run dry.²,³

122

123 In a 2004 report entitled "Bad Bugs, No Drugs", the Infectious Diseases Society of America
124 (IDSA) imagined a catastrophic scenario with an explosive epidemic of 220,000 cases and
125 1,730 deaths caused by a multidrug-resistant non-typhoidal *Salmonella*, resistant, in
126 particular, to both ESCs and fluoroquinolones. This choice was based on the following
127 observations (i) *Salmonella* is a prevalent zoonotic agent causing an estimated 1.7 million
128 infections, resulting in 2,800 deaths per year in high-income regions of North America in
129 2006,⁴ (ii) *Salmonella* can cause major food-borne outbreaks, such as that in the US in 1994
130 associated with manufactured ice cream contaminated with *Salmonella enterica* serotype
131 Enteritidis, which caused sickness in an estimated 224,000 people,⁵ (iii) fluoroquinolones,
132 including ciprofloxacin, and ESCs are the drugs of choice for treating severe *Salmonella*
133 infections and for people at risk of such infections (infants, the elderly and
134 immunocompromised patients), and (iv) infections with drug-resistant *Salmonella* are
135 associated with higher morbidity and mortality.⁶

136

137 We previously reported the international emergence of a multidrug-resistant *S. enterica*
138 serotype Kentucky (*Salmonella* Kentucky) strain, identified as being multilocus sequence
139 type (MLST) ST198 and as belonging to *Xba*I pulsed-field gel electrophoresis (PFGE) cluster
140 X1.⁷ *Salmonella* Kentucky ST198-X1 isolates were resistant to several antimicrobial drugs,
141 including ciprofloxacin (minimal inhibitory concentration [MIC] ≥ 4 mg/L), which is a very
142 unusual resistance trait in *Salmonella*.⁸,⁹ The first ciprofloxacin-resistant *Salmonella*
143 Kentucky (*Salmonella* Kentucky CIP<sup>R</sup>) to be identified was isolated from a French tourist
144 who visited Egypt in 2002. From then until 2008, the *Salmonella* surveillance systems in
145 France, England, and Denmark detected 489 cases of infection with this strain in people who
146 had travelled to or stayed in Africa or the Middle East.⁷ Hospitalisation was more frequent
147 among patients infected with CIP<sup>R</sup> Kentucky (mean age, 36 years) than among those infected
148 with Kentucky strains susceptible to ciprofloxacin.⁷

149

150 All *Salmonella* Kentucky CIP<sup>R</sup> isolates in our survey were susceptible to ESCs. However, one
151 case report described a Belgian traveller infected with *Salmonella* Kentucky CIP<sup>R</sup> during a
152 trip to Libya in 2005, who required treatment with meropenem due to ESC resistance (CTX-
153 M-1 ESBL production) after multiple treatment failures for a severe infection.¹⁰
154 The aim of this study was to monitor recent trends in the global epidemiology and
155 antimicrobial resistance of the *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup> strain. The work was
156 conducted in parallel in France, where this infection occurred mostly in travellers or migrants,
157 and in Morocco, where most of the French travellers or migrants had acquired the infection.
This study identified highly drug-resistant (HDR) isolates, present in both France and Morocco since 2009. These CIP<sup>R</sup> isolates acquired in the Mediterranean area produce various carbapenemases, cephamycinase, or ESBLs. This report indicates that *Salmonella* has taken a major step towards panresistance and suggests that the catastrophic scenario imagined by the IDSA might become all too real in the near future.
164 MATERIALS & METHODS

165

166 Data for human *Salmonella* infections

167 France

168 We used data from the French National Reference Centre for *Salmonella* (FNRC-Salm),
169 established since 1947. During the 2000s, the FNRC-Salm network included a stable number
170 of approximately 1,400 hospital and private clinical laboratories. In 2008, an unpublished
171 survey of all French clinical laboratories (n=3,375, response rate of 95%) estimated that about
172 65% of all human *Salmonella* isolates in France were reported to the FNRC-Salm. Basic
173 epidemiological data (date and site of isolation, sex and age of the patient, and international
174 travel) were recorded for each isolate. From 2000 to 2011, 128,836 serotyped *Salmonella*
175 isolates were registered at the FNRC-Salm, including 954 non-repeated *Salmonella* Kentucky
176 isolates (0.7% of all *Salmonella* isolates).

177

178 Morocco

179 We used 2003-2011 data from two sites in Casablanca, the largest city in Morocco. The first
180 site was the Microbiology Laboratory of the University Hospital Centre Ibn Rochd (UHCIR),
181 Casablanca, a 1,700-bed teaching hospital. The second site was the Pasteur Institute of
182 Morocco (PIM), which receive clinical strains of *Salmonella* for serotyping from private
183 laboratories. Between 2003 and 2011, 226 *Salmonella* isolates were obtained and serotyped,
184 including 30 non-repeated *Salmonella* Kentucky isolates (12.8% of all *Salmonella* isolates).

185

186 Microbiological investigations

187 Bacterial isolates
188 All but two (which could not be subcultured) of the 954 *Salmonella* Kentucky isolates

189 obtained from humans between 2000 and 2011 in France were included in this study. Thirty

190 (26 from UHCIR and 4 from PIM) *Salmonella* Kentucky isolates collected from humans in

191 Casablanca, Morocco between 2003 and 2011 were also studied. One additional isolate from
192 the FNRC-Salm was studied: one of serotype Saintpaul isolated from a patient co-infected
193 with *Salmonella* Kentucky in 2009.

194

195 *Antimicrobial susceptibility testing*

196 Antimicrobial susceptibility testing (AST) was performed on all *Salmonella* isolates, by the
disk diffusion method with a panel of 32 antimicrobial agents (Bio-Rad, Marnes-La-Coquette,
197 France).⁷ The MICs of ceftriaxone, ceftazidime, imipenem, ertapenem, meropenem,
198 ciprofloxacin, azithromycin, colistin, and tigecycline were determined by Etests (AB Biodisk,
199 Solna, Sweden). Results were interpreted with the Antibiogram Committee of the French
200 Society for Microbiology (CA-SFM) (www.sfm-microbiologie.org/) breakpoints. In
201 particular, susceptible isolates were defined as having a MIC ≤ 0.5 mg/L for ciprofloxacin,
202 and resistant isolates were defined as having a MIC > 1 mg/L for ciprofloxacin, regardless of
203 isolate source (i.e., intestinal or extraintestinal). Isolates were defined as highly drug-resistant
204 if they were resistant to at least four antibiotic classes, including both fluoroquinolones (i.e.,
205 ciprofloxacin) and ESCs (i.e., ceftriaxone and/or ceftazidime).
206

207

208 *Molecular typing*

209 PulseNet standard pulsed-field gel electrophoresis (PFGE) of XbaI-digested chromosomal
210 DNA and multilocus sequence typing (MLST) were performed as previously described.⁷

211

212 *Determination of resistance mechanisms*
213 The presence of beta-lactam resistance genes (*bla*<sub>TEM</sub>, *bla*<sub>SHV</sub>, *bla*<sub>OXA-1</sub> group, *bla*<sub>CMY</sub>, *bla*<sub>CTX-M</sub>, *bla*<sub>OXA-48</sub>, *bla*<sub>VIM</sub>, *bla*<sub>NDM</sub>, and *bla*<sub>KPC</sub>), plasmid-mediated quinolone resistance genes, (*qnrA*, *qnrB*, *qnrS*, *qnrD*, *aacA4*-cr (also known as *aac(6')-Ib-cr*) and *qepA*), macrolide resistance genes (*ermA*, *ermB*, *ermC*, *mph(A)*), *ereA*, *ereB*, *mrsA*, *mrsB*, *mefA*, and *mefE*),
214
215
216
217 aminoglycoside resistance genes (*armA*, *rmtA*, *rmtB*, *rmtC*, *rmtD*, and *rpmA*), class 1 integron
218
gene cassettes and *Salmonella* genomic island 1 (SGI1) was assessed by PCR, as previously
described.<sup>7,11-14</sup>
219
220

220

221 The quinolone resistance-determining region (QRDR) of *gyrA*, *gyrB*, *parC* and *parE* (encoding subunits of the DNA gyrase and the topoisomerase IV) was sequenced, as previously described.⁷ The nucleotide and deduced amino-acid sequences were analysed and compared with sequences available from the National Center for Biotechnology Information website (http://www.ncbi.nlm.nih.gov).

226

227 We assessed resistance transfer by mating, with ESBL, cephامycinase and carbapenemase
228 producers, using liquid and solid media, with *E. coli* K-12 BM14 resistant to sodium azide as
229 the recipient strain. Transconjugants were selected on Drigalski agar (Bio-Rad) supplemented
230 with ceftriaxone (4 mg/L), ceftazidime (16 mg/L), or imipenem (3 mg/L) plus sodium azide
231 (500 mg/L). Three *E. coli* transconjugants were arbitrarily selected in each experiment. We
232 used S1 nuclease treatment and PFGE to determine the sizes of bacterial plasmids accurately,
233 and PCR-based replicon typing analysis was performed, as previously described.<sup>15</sup>

234
235 **RESULTS**

236

237 **Occurrence of *Salmonella* Kentucky CIP<sup>R</sup> in humans**

238 *France*

239 Of the 497 isolates of *Salmonella* Kentucky obtained in France between 2000 and 2008, 200

240 (40.2%) were resistant to ciprofloxacin (previously reported in reference 7). For the period

241 2009-2011, 376 (82.6%) of the 455 *Salmonella* Kentucky tested were CIP<sup>R</sup> (Figure). This

242 near doubling of the number of *Salmonella* Kentucky CIP<sup>R</sup> isolates obtained, in a third of the

243 time, with a stable network of laboratories, against a backdrop of a general decrease in the

244 number of isolations of *Salmonella* (≈11,000 clinical isolates received per year during the

245 period 2000-2008 vs ≈10,000 during the period 2009-2011), indicates that this *Salmonella*

246 Kentucky CIP<sup>R</sup> strain continued to circulate and spread.

247

248 Travel information was available for 371 patients (64.5%) infected with CIP<sup>R</sup> Kentucky

249 during the period 2000-2011 (Table 1). Of these 371 patients, 338 (91.1%) had travelled

250 internationally in the 15 days before the onset of illness, whereas the remaining 33 patients

251 had not. Most of the patients seen between 2002 and 2005 had travelled to North-East or East

252 Africa. Since 2006, patients have been reporting travel to North-East and East Africa, North

253 Africa, West Africa, and the Middle East. Since 2009, the area of infection has extended to

254 include India.

255

256

257
283 *Salmonella* Kentucky CIP<sup>R</sup> isolates belonged to the ST198-X1 strain, and carried the *gyrA*

284 and *parC* mutations previously encountered in Kentucky isolates from Egypt and West

285 Africa.⁷ The three isolates also contained the phosphotransferase *mph(A)* gene conferring

286 high-level resistance to azithromycin. The three isolates presented different resistance

287 profiles, due to the acquisition/loss of various R plasmids and also, probably, due to IS26

288 rearrangements of the SGI1.⁷ The first isolate was resistant to ESCs due to the presence of the

289 *bla*<sub>CMY-2</sub> gene, whereas the most recent isolate, collected one year later, contained the *bla*<sub>OXA-48</sub>

290 carbapenemase gene. All four isolates were susceptible to colistin and tigecycline.

291

292 *Highly drug-resistant* *Salmonella* *Kentucky isolates producing VIM-2 in Morocco in 2010*

293 Five of the 30 *Salmonella* Kentucky isolates obtained in Casablanca, Morocco, between 2003

294 and 2011 (16.6%) were ESC<sup>R</sup>. These five *Salmonella* Kentucky ST198-X1 ESC<sup>R</sup>-CIP<sup>R</sup>

295 isolates had decreased susceptibility to imipenem (MIC range, 1-3 mg/L). They all contained

296 the *bla*<sub>VIM-2</sub> gene within In58,<sup>16</sup> itself carried on a 30-kb plasmid. Three isolates originated

297 from patients hospitalised in three different reanimation wards (one blood culture, two urine

298 cultures) of the UHCIR during January 2010, the other two isolates being obtained from stool

299 cultures performed at the PIM in January and August 2010.

300

301
302 DISCUSSION

303 We report a new step towards pan-antimicrobial resistance in *Salmonella*, a major foodborne
304 pathogen found worldwide, which can cause life-threatening infections. The *Salmonella*
305 Kentucky ST198-X1 isolates reported here are resistant to both fluoroquinolones and ESCs
306 (except for the OXA-48-producing strain), and some also display full or intermediate
307 resistance to carbapenems. Many are also resistant to most aminoglycosides (*armA* gene) and
308 to azithromycin (*mph(A)* gene). *Salmonella* Kentucky ST198-X1 is a particularly successful
309 strain that has accumulated various chromosomal resistance determinants since the mid-
310 1990s, with the integration of the *Salmonella* genomic island 1 (encoding resistance to
311 multiple antimicrobial drugs, including amoxicillin, gentamicin, and sulfonamides), followed
312 by cumulative mutations in the *gyrA* and *parC* genes, leading to resistance to nalidixic acid,
313 and then to ciprofloxacin, in 2002. This strain was mostly identified in Egypt before 2005,⁷
314 but has since spread rapidly throughout Africa and the Middle East. The slight decrease in
315 isolation rates for this strain in 2011 probably resulted from the “Arab Spring”, which may
316 have discouraged travel to the area in which this strain is endemic. Thus, 150 *Salmonella*
317 Kentucky CIP<sup>R</sup> isolates were obtained at the FNRC-Salm in 2012 (data not shown), a number
318 similar to that obtained in 2010. The *Salmonella* Kentucky CIP<sup>R</sup> strain was first identified in
319 the Indian subcontinent in 2009, and a pattern of current spread across Asia is also suggested
320 by the isolation of two *Salmonella* Kentucky CIP<sup>R</sup> isolates from French patients reporting
321 travel to Vietnam and Indonesia in 2012 (data not shown). As the geographic spread of this
322 strain has been predicted by a French surveillance system, it may be partially biased by the
323 preferred destinations of French travellers and particular migrant populations with historical
324 links to France. Where possible, these data should be confirmed by local studies.
325

325
This epidemic was previously associated with a livestock (autochthonous poultry) reservoir of this *Salmonella* Kentucky CIP<sup>R</sup> strain in Africa. It was suggested that the common use of fluoroquinolones in poultry and the lack of both laboratory-based surveillance of infections and control measures in the countries in which this strain circulates played a role in the rapid spread of this strain after 2002.<sup>7</sup> A survey performed on 92 poultry farms in Sudan, East Africa, in 2008 revealed that enrofloxacin, a fluoroquinolone, was commonly added to the drinking water on 14% of the farms surveyed.<sup>17</sup> Both here and in our previous study, ~11% of the patients reported no history of travel outside Europe, suggesting that these infections may have resulted from the consumption of contaminated foods or secondary contamination in Europe. Indeed, contaminated spices from North Africa have previously been identified in France and the US.<sup>7</sup> This strain also seems to have become established in some European flocks, another major source of concern. In 2010, *Salmonella* Kentucky CIP<sup>R</sup> isolates were found in turkey meat products in Germany and in turkey meat or flocks in Poland.<sup>18,19</sup> One of the *Salmonella* Kentucky CIP<sup>R</sup> isolates recovered from a flock in Poland in 2010 was also resistant to ESCs, due to the production of a CTX-M ESBL.<sup>19</sup>

The diversity of the recently acquired β-lactamases (CTX-M ESBLs, CMY-2 AmpC, and VIM-2 and OXA-48 carbapenemases) suggests that the increasingly common *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup> strain has been “collecting” genes for resistance to ESCs and carbapenems. Resistance to carbapenems is otherwise extremely rare in *Salmonella* spp. (panel). The simultaneous presence of ESCs and carbapenem determinants (CMY-2 and OXA-48) was even documented in this study in *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup> isolated from a single patient.
A similar scenario, but without the acquisition of carbapenemase, occurred in Taiwan for S. 350
*enterica* serotype Choleraesuis (*Salmonella* Choleraesuis), a serotype acquired from pigs and 351
associated with extraintestinal infection in humans.⁸ The first CIP<sup>R</sup> isolates appeared in 2000 352
and, in the third quarter of 2001, 60% of the *Salmonella* Choleraesuis isolates from humans 353
were CIP<sup>R</sup>.⁸ This trait was attributed to the use of enrofloxacin in pigs. Additional resistance 354
to ESCs mediated by the cephamycinase CMY-2 has appeared since 2002.²⁶ This enzyme is 355
frequent in many *Salmonella* serotypes, including Newport in the US, where its emergence 356
has been associated with the use of ceftiofur, an ESC licensed for use in cattle, pigs, and other 357
food animals.²⁷ Unlike *Salmonella* Choleraesuis CIP<sup>R</sup> and Newport ESC<sup>R</sup>, *Salmonella* 358
Kentucky ST198-X1 CIP<sup>R</sup> is not restricted to a single country or region, rendering control 359
measures in livestock more difficult. 360

We found that *Salmonella* Kentucky ST198-X1 had a broad geographic distribution, 361
overlapping with that of certain plasmid-borne carbapenemases, such as OXA-48 and 362
VIM.¹²,¹⁶ This makes it likely that carbapenemase-producing *Salmonella* will become more 363
frequent in the Mediterranean area in the near future, particularly if such carbapenemase 364
producers become established in livestock, as previously observed for ESBL- and 365
cephamycinase-producing *Salmonella* in industrialised countries.²⁷⁻²⁹ Indeed, isolation of the 366
VIM-1-producing S. *enterica* serotype Infantis from two pig farms and one poultry farm in 367
Germany was reported in 2012.²⁵ 368

Another issue is the difficulty of phenotypic detection for several carbapenemase producers.¹² 370
This problem is particularly difficult for OXA-48, which weakly hydrolyses carbapenems but 371
not ESCs in the absence of additional ESBL and/or cephamycinase and permeability defects. 372
Indeed, carbapenem MICs were found to be low for the carbapenemase producers. Two 373
374
isolates, one OXA-48-positive and one VIM-2-positive Kentucky isolate, were even classified
as susceptible to the three carbapenems tested, on the basis of the CLSI or CA-SFM
breakpoints. The use of rapid diagnostic tests, such as the recently developed Carba NP test,
would facilitate the early detection of carbapenemase producers.³⁰

In conclusion, this report highlights the recent emergence of HDR *Salmonella* and the need to screen *Salmonella* isolated either from humans or food-producing animals for carbapenemase producers. The main types of carbapenemase (KPC, OXA-48, NDM, VIM) have now been identified in *Salmonella*, and half of these enzymes have been found in the *Salmonella* Kentucky ST198-X1 strain. National and international health, food and agricultural authorities need to recognise rapidly the potential risk to Public Health posed by *Salmonella* Kentucky ST198-X1 CIP<sup>R</sup>, so that *Salmonella* Kentucky CIP<sup>R</sup> can be included, as a new targeted strain, in current national programmes for the control of *Salmonella* in poultry.

## AUTHOR CONTRIBUTIONS

Conceived and designed the experiments: SLH and FXW. Performed the experiments: DH, LS, DE, VG. Contributed reagents/materials/analysis tools: BB, KZ. Analysed the data: SLH and FXW. Wrote the paper: SLH and FXW. Reviewed, critiqued and offered comments on the text: DH, BB, KZ.

## ACKNOWLEDGEMENTS

We thank Dr. Isabelle Loirat for providing clinical information and Mr. Erwan Trochu for expert technical assistance. We thank all corresponding laboratories of the French National
400 Reference Centre for *E. coli*, *Shigella*, and *Salmonella*.

401 The French National Reference Centre for *E. coli*, *Shigella*, and *Salmonella* is funded by the

402 Institut Pasteur and the Institut de Veille Sanitaire. Dorothée Harrois was supported by a grant

403 from "La Fondation pour la Recherche Médicale". The "Unité des Bactéries Pathogènes

404 Entériques" belongs to the "Integrative Biology of Emerging Infectious Diseases" Laboratory

405 of Excellence funded by the French Government "Investissement d'Avenir" programme

406 (grant no. ANR-10-LABX-62-IBEID).

407

408

409 CONFLICTS OF INTEREST

410 All authors declare that they have no competing interests or conflicts of interest.

411

412 REFERENCES

413 1. Arias CA, Murray BE. Antibiotic-resistant bugs in the 21st century--a clinical super-challenge. *N Engl J Med* 2009; **360**: 439-43.

415 2. Walsh TR. The emergence and implications of metallo-β-lactamases in Gram-negative bacteria. *Clin Microbiol Infect* 2005; **11**: 2-9.

417 3. Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging carbapenemases. *Trends Microbiol* 2011; **18**: 588-95.

419 4. Majowicz SE, Musto J, Scallan E, et al. The global burden of nontyphoidal *Salmonella* gastroenteritis. *Clin Infect Dis* 2010; **50**: 882-9.

421 5. Hennessy TW, Hedberg CW, Slutsker L, et al. A national outbreak of *Salmonella enteritidis* infections from ice cream. The Investigation Team. *N Engl J Med* 1996; **334**: 1281-6.

424 6. Mølbak K. Human health consequences of antimicrobial drug-resistant *Salmonella* and other foodborne pathogens. *Clin Infect Dis* 2005; **41**: 1613-20.
426

7. Le Hello S, Hendriksen RS, Doublet B, et al. International spread of an epidemic population of *Salmonella enterica* serotype Kentucky ST198 resistant to ciprofloxacin. *J Infect Dis* 2011; **204**: 675-84.

427

428

429

8. Chiu CH, Wu TL, Su LH, et al. The emergence in Taiwan of fluoroquinolone resistance in *Salmonella enterica* serotype Choleraesuis. *N Engl J Med* 2002; **346**: 413-9.

430

431

432

9. Olsen SJ, DeBess EE, McGivern TE, et al. A nosocomial outbreak of fluoroquinolone-resistant *Salmonella* infection. *N Engl J Med* 2001; **344**: 1572-9.

433

434

10. Collard JM, Place S, Denis O, et al. Travel-acquired salmonellosis due to *Salmonella* Kentucky resistant to ciprofloxacin, ceftriaxone and co-trimoxazole and associated with treatment failure. *J Antimicrob Chemother* 2007; **60**: 190-2.

435

436

437

11. Sutcliffe J, Grebe T, Tait-Kamradt A, Wondrack L. Detection of erythromycin-resistant determinants by PCR. *Antimicrob Agents Chemother* 1996; **40**: 2562-6.

438

439

12. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. *Emerg Infect Dis* 2011; **17**: 1791-8.

440

441

13. Accou-Demartin M, Gaborieau V, Song Y, et al. *Salmonella enterica* serotype Typhi with nonclassical quinolone resistance phenotype. *Emerg Infect Dis* 2011; **17**: 1091-4.

442

443

14. Fritsche TR, Castanheira M, Miller GH, et al. Detection of methyltransferases conferring high-level resistance to aminoglycosides in Enterobacteriaceae from Europe, North America, and Latin America. *Antimicrobial Agents Chemother* 2008; **52**: 1843-5.

444

445

446

447

15. Fabre L, Delauné A, Espié E, et al. Chromosomal integration of the extended-spectrum beta-lactamase gene *bla*<sub>CTX-M-15</sub> in *Salmonella enterica* serotype Concord isolates from internationally adopted children. *Antimicrob Agents Chemother* 2009; **53**: 1808-16.

448

449

450
16. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. *J Antimicrob Chemother* 2012; **67**: 1597-606.

17. Sirdar MM, Picard J, Bisschop S, Gummow B. A questionnaire survey of poultry layer farmers in Khartoum State, Sudan, to study their antimicrobial awareness and usage patterns. *Onderstepoort J Vet Res* 2012; **79**: E1-8.

18. Beutlich J, Guerra B, Schroeter A, Arvand M, Szabo I, Helmuth R. [Highly ciprofloxacin resistant *Salmonella enterica* serovar Kentucky isolates in turkey meat and a human patient] in German. *Berl Munch Tierarztl Wochenschr* 2012; **125**: 89-95.

19. Wasyl D, Hoszowski A. First isolation of ESBL-producing *Salmonella* and emergence of multiresistant *Salmonella* Kentucky in turkey in Poland. *Food Research International* 2012; **45**: 958-61

20. Armand-Lefèvre L, Leflon-Guibout V, Bredin J, et al. Imipenem resistance in *Salmonella enterica* serovar Wien related to porin loss and CMY-4 β-lactamase production. *Antimicrob Agents Chemother* 2003; **47**: 1165-8.

21. Miriagou V, Tzouvelekis LS, Rossiter S, Tzelepi E, Angulo FJ, Whichard JM. Imipenem resistance in a *Salmonella* clinical strain due to plasmid-mediated class A carbapenemase KPC-2. *Antimicrob Agents Chemother* 2003; **47**: 1297-300.

22. Su LH, Wu TL, Chiu CH. Development of carbapenem resistance during therapy for non-typhoid *Salmonella* infection. *Clin Microbiol Infect* 2012; **18**: E91-4.

23. Savard P, Gopinath R, Zhu W, et al. First NDM-positive *Salmonella* sp. strain identified in the United States. *Antimicrob Agents Chemother* 2011; **55**: 5957-8.

24. Cabanes F, Lemant J, Picot S, et al. Emergence of Klebsiella pneumoniae and *Salmonella* metallo- β-lactamase (NDM-1) producers on Reunion Island. *J Clin Microbiol* 2012; **50**: 3812.
475

25. Fischer J, Rodríguez I, Schmoger S, et al. *Salmonella enterica* subsp. *enterica* producing VIM-1 carbapenemase isolated from livestock farms. *J Antimicrob Chemother* 2013; **68**: 478-80.

476

477

478

26. Su LH, Teng WS, Chen CL, et al. Increasing ceftriaxone resistance in Salmonellae, Taiwan. *Emerg Infect Dis* 2011; **17**: 1086-90.

479

480

27. Gupta A, Fontana J, Crowe C, et al. Emergence of multidrug-resistant *Salmonella enterica* serotype Newport infections resistant to expanded-spectrum cephalosporins in the United States. *J Infect Dis* 2003; **188**: 1707-16.

481

482

483

28. Rodríguez I, Barownick W, Helmuth R, et al. Extended-spectrum β-lactamases and AmpC β-lactamases in ceftiofur-resistant *Salmonella enterica* isolates from food and livestock obtained in Germany during 2003-07. *J Antimicrob Chemother* 2009; **64**: 301-9.

484

485

486

487

29. Bertrand S, Weill FX, Cloeckaert A, et al. Clonal emergence of extended-spectrum beta-lactamase (CTX-M-2)-producing *Salmonella enterica* serovar Virchow isolates with reduced susceptibilities to ciprofloxacin among poultry and humans in Belgium and France (2000 to 2003). *J Clin Microbiol* 2006; **44**: 2897-903.

488

489

490

491

30. Nordmann P, Dortet L, Poirel L. Rapid detection of carbapenemase-producing Enterobacteriaceae. *Emerg Infect Dis* 2012; **18**: 1503-7.

492

493

494

495
<table><caption>**Table 1:** Countries visited by patients infected with *S. enterica* serotype Kentucky resistant to ciprofloxacin in the 15 days before the onset of illness (data from the French National Reference Centre for *Salmonella*)</caption><thead><tr><th>Country</th><th>2002-2005</th><th>2006-2008</th><th>2009-2011</th><th>Total</th></tr></thead><tbody><tr><td><strong>Africa</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Not specified</td><td></td><td>3</td><td>2</td><td>5</td></tr><tr><td>Algeria</td><td></td><td>9</td><td>60</td><td>69</td></tr><tr><td>Cameroon</td><td></td><td>2</td><td>1</td><td>3</td></tr><tr><td>Djibouti</td><td></td><td>1</td><td>2</td><td>3</td></tr><tr><td>Egypt</td><td>11</td><td>11</td><td>7</td><td>29</td></tr><tr><td>Ethiopia</td><td></td><td></td><td>2</td><td>2</td></tr><tr><td>Ivory Coast</td><td></td><td></td><td>6</td><td>6</td></tr><tr><td>Kenya</td><td>2</td><td>1</td><td></td><td>3</td></tr><tr><td>Libya</td><td></td><td>2</td><td>1</td><td>3</td></tr><tr><td>Mauritania</td><td></td><td></td><td>2</td><td>2</td></tr><tr><td>Morocco</td><td></td><td>69</td><td>78</td><td>147</td></tr><tr><td>Senegal</td><td></td><td></td><td>7</td><td>7</td></tr><tr><td>Sudan</td><td>1</td><td></td><td></td><td>1</td></tr><tr><td>Tanzania</td><td>1</td><td>2</td><td></td><td>3</td></tr><tr><td>Tunisia</td><td></td><td>5</td><td>21</td><td>26</td></tr><tr><td><strong>Middle East</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Iran</td><td></td><td>1</td><td></td><td>1</td></tr><tr><td>Iraq</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td>Israel</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td>Lebanon</td><td></td><td>2</td><td>2</td><td>4</td></tr><tr><td>Saudi Arabia</td><td></td><td>1</td><td></td><td>1</td></tr><tr><td>Syria</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td>Turkey</td><td></td><td>2</td><td>2</td><td>4</td></tr><tr><td><strong>Asia</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>India</td><td></td><td></td><td>8</td><td>8</td></tr><tr><td><strong>North America</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Canada</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td><strong>Europe</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>France†</td><td></td><td>6</td><td>27</td><td>33</td></tr><tr><td>Croatia</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td>Greece</td><td></td><td></td><td>1</td><td>1</td></tr><tr><td>Spain</td><td></td><td></td><td>5</td><td>5</td></tr><tr><td><strong>Total</strong></td><td>15</td><td>117</td><td>239</td><td>371</td></tr></tbody></table>

<footnote>†France is indicated as the country of infection in cases of notification of an absence of international travel for up to 2 months before the onset of symptoms</footnote>
<table><caption>**Table 2:** Antimicrobial drug-resistant *Salmonella* isolates included in this study</caption><thead><tr><th rowspan="2">Isolate</th><th rowspan="2">Serotype</th><th rowspan="2">Date of isolation</th><th rowspan="2">Source<sup>a</sup></th><th rowspan="2">Country of infection</th><th rowspan="2">Antimicrobial resistance profiles<sup>b</sup></th><th rowspan="2">MLST/ PFGE</th><th rowspan="2">SGI1</th><th colspan="10">MIC (mg/L)<sup>c</sup></th></tr><tr><th>Cro</th><th>Caz</th><th>IMP</th><th>ETP</th><th>MEM</th><th>CIP</th><th>Azi</th><th>CST</th><th>TGC</th></tr></thead><tbody><tr><td colspan="14">Isolates recovered through the French national <i>Salmonella</i> surveillance system</td></tr><tr><td>09-8391</td><td>Kentucky</td><td>02 Nov 09</td><td>F, 65y, stool, H</td><td>Morocco</td><td>A Cro Caz Fox NaI CIP</td><td>ST198/X1e</td><td>+</td><td>64</td><td>48</td><td>0.38</td><td>0.064</td><td>0.064</td><td>32</td><td>8</td><td>0.25</td><td>0.5</td></tr><tr><td>09-9322</td><td>Kentucky</td><td>16 Dec 09</td><td>F, 70y, stool, N</td><td>Egypt</td><td>A Cro Caz Fox S Sp K T N Chl Sul Tmp NaI CIP Azi</td><td>ST198/X1w</td><td>+</td><td>24</td><td>64</td><td>0.5</td><td>0.023</td><td>0.047</td><td>12</td><td>128</td><td>0.19</td><td>0.38</td></tr><tr><td>10-0720</td><td>Kentucky</td><td>31 Jan 10</td><td>F, 25y, stool, H</td><td>Turkey</td><td>A Cro S Sp G Sul Te NaI CIP</td><td>ST198/X1b</td><td>+</td><td>64</td><td>4</td><td>0.25</td><td>0.016</td><td>0.064</td><td>16</td><td>4</td><td>0.25</td><td>1</td></tr><tr><td>10-5456</td><td>Kentucky</td><td>13 Aug 10</td><td>F, 7y, stool, H</td><td>Algeria</td><td>A Cro Caz S Sp K T N G Ak Chl Sul Tmp NaI Cip Azi</td><td>ST198/X1a</td><td>+</td><td>>256</td><td>>256</td><td>0.38</td><td>0.023</td><td>0.047</td><td>12</td><td>32</td><td>0.25</td><td>0.5</td></tr><tr><td colspan="14">Isolates recovered through the survey in Casablanca, Morocco</td></tr><tr><td>10-1923</td><td>Kentucky</td><td>04 Jan 10</td><td>M, 25y, urine, H</td><td>Morocco</td><td>A Cro Caz Fox IMP* S Sp K T G Sul Te NaI CIP</td><td>ST198/X1j</td><td>+</td><td>256</td><td>192</td><td>3</td><td>1.5</td><td>0.25</td><td>12</td><td>4</td><td>0.25</td><td>1</td></tr><tr><td>10-1922</td><td>Kentucky</td><td>07 Jan 10</td><td>M, 20y, blood, H</td><td>Morocco</td><td>A Cro Caz Fox IMP* S Sp K T N G Ak Is Sul Te NaI CIP</td><td>ST198/X1m</td><td>+</td><td>24</td><td>24</td><td>3</td><td>0.5</td><td>0.25</td><td>12</td><td>6</td><td>0.25</td><td>1</td></tr><tr><td>10-1924</td><td>Kentucky</td><td>21 Jan 10</td><td>M, 92y, urine, H</td><td>Morocco</td><td>A Cro Caz Fox IMP* S Sp K T N G Sul Te NaI CIP</td><td>ST198/X1j</td><td>+</td><td>256</td><td>96</td><td>3</td><td>3</td><td>1</td><td>16</td><td>6</td><td>0.25</td><td>1</td></tr><tr><td>10-1925</td><td>Kentucky</td><td>24 Jan 10</td><td>M, >18y, stool, N</td><td>Morocco</td><td>A Cro Caz Fox S Sp K T N G Ak Is Sul Te NaI CIP</td><td>ST198/X1j</td><td>+</td><td>32</td><td>24</td><td>1</td><td>0.19</td><td>0.25</td><td>8</td><td>4</td><td>0.25</td><td>0.75</td></tr><tr><td>10-1926</td><td>Kentucky</td><td>25 Aug 10</td><td>M, >18y, stool, N</td><td>Morocco</td><td>A Cro Caz Fox IMP* S Sp K T G Sul Te NaI CIP</td><td>ST198/X1j</td><td>+</td><td>>256</td><td>48</td><td>2</td><td>0.75</td><td>1</td><td>8</td><td>4</td><td>0.5</td><td>1</td></tr><tr><td colspan="14">Isolates recovered from a single patient<sup>‡</sup></td></tr><tr><td>09-7981</td><td>Saintpaul</td><td>16 Oct 09</td><td>F, 69y, blood, H</td><td>Egypt</td><td>A IMP*</td><td>ST1670</td><td>-</td><td>1.5</td><td>2</td><td>3</td><td>1</td><td>1.5</td><td>0.023</td><td>2</td><td>0.25</td><td>0.38</td></tr><tr><td>10-0305</td><td>Kentucky</td><td>07 Jan 10</td><td>F, 70y, stool, N</td><td>Egypt</td><td>K Chl Tmp NaI CIP Azi</td><td>ST198/X1w</td><td>+</td><td>0.094</td><td>0.50</td><td>0.38</td><td>0.008</td><td>0.023</td><td>12</td><td>48</td><td>0.19</td><td>0.5</td></tr><tr><td>11-0664</td><td>Kentucky</td><td>28 Jan 11</td><td>F, 71y, stool, N</td><td>Egypt</td><td>A NaI CIP Azi</td><td>ST198/X1w</td><td>+</td><td>0.125</td><td>0.25</td><td>0.75</td><td>0.5</td><td>0.19</td><td>8</td><td>32</td><td>0.50</td><td>0.50</td></tr></tbody></table>

<sup>a</sup>F, female; M, male; y, years (age); H, hospitalised; N, not hospitalised

<sup>b</sup>A, amoxicillin; Cro, ceftriaxone; Caz; ceftazidime; Fox, cefoxitin; IMP, imipenem (*, intermediate resistance according to CA-SFM, resistance according to CLSI); ETP, ertapenem; MEM, meropenem; S, streptomycin; Sp, spectinomycin; K, kanamycin; T, tobramycin; N, netilmicin; G, gentamicin; Ak, amikacin; Is, isepamicin; Chl, chloramphenicol; Sul, sulfamethoxazole; Tmp, trimethoprim; NaI, nalidixic acid; Cip, ciprofloxacin; Azi, azithromycin; CST, colistin; TGC, tigecycline

<sup>c</sup>CA-SFM and CLSI (M100 S22) breakpoints for carbapenems: IMP and MEM (CA-SFM, S ≤ 2 mg/L, R > 8 mg/L; CLSI, S ≤ 1 mg/L, R ≥ 4 mg/L); ETP (CA-SFM, S ≤ 0.5 mg/L, R > 1 mg/L; CLSI, S ≤ 0.5 mg/L, R ≥ 2 mg/L). For categorisation, Etest MICs between standard dilutions were rounded up to the next two-fold dilution

<sup>d</sup>Isolate 09-9322 recovered by the French national surveillance system was also isolated from this single patient who had travelled to Egypt
<table><caption>**Table 3:** Mechanisms of resistance to antimicrobial drugs in the antimicrobial drug-resistant *Salmonella* isolates included in this study</caption><thead><tr><th rowspan="3">Isolate</th><th rowspan="3">Serotype</th><th colspan="6">Main determinants of resistance to:<br>(incompatibility group, plasmid size)</th><th rowspan="3">Class 1 integrons</th></tr><tr><th colspan="3">ESC</th><th colspan="3">Ciprofloxacin</th></tr><tr><th>Carbapenems</th><th>GyrA</th><th>ParC</th><th>PMQR</th><th>Azi</th><th>Aminoglycosides</th></tr></thead><tbody><tr><td colspan="9">Isolates recovered through the French national <i>Salmonella</i> surveillance system</td></tr><tr><td>09-8391</td><td>Kentucky</td><td>bla<sub>CMY-2</sub> (IncII, 90 kb)</td><td>-</td><td>Ser83Phe, Asp87Asn</td><td>Ser80Ile</td><td>-</td><td>-</td><td>-</td></tr><tr><td>09-9322</td><td>Kentucky</td><td>bla<sub>CMY-2</sub> (IncII, 90 kb; IncA/C, 200 kb)</td><td>-</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>mph(A) (NT)</td><td>-</td><td>1.8 kb (dfrA12, aadA2)</td></tr><tr><td>10-0720</td><td>Kentucky</td><td>bla<sub>CTX-M-1</sub> (IncII, 90 kb)</td><td>-</td><td>Ser83Phe, Asp87Asn</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7)</td></tr><tr><td>10-5456</td><td>Kentucky</td><td>bla<sub>CTX-M-15</sub> (IncL/M, 90 kb)</td><td>-</td><td>Ser83Phe, Asp87Asn</td><td>Ser80Ile</td><td>mph(A) (NT)</td><td>armA (IncL/M, 90 kb)</td><td>1.8 kb (dfrA12, aadA2)</td></tr><tr><td colspan="9">Isolates recovered through the survey in Casablanca, Morocco</td></tr><tr><td>10-1923</td><td>Kentucky</td><td>-</td><td>bla<sub>VIM-2</sub> (UT, 30 kb)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7), 3 kb (aacA7, bla<sub>VIM-2</sub>, aacC1, aacA4)</td></tr><tr><td>10-1922</td><td>Kentucky</td><td>-</td><td>bla<sub>VIM-2</sub> (IncW, 30 kb)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7), 3 kb (aacA7, bla<sub>VIM-2</sub>, aacC1, aacA4)</td></tr><tr><td>10-1924</td><td>Kentucky</td><td>-</td><td>bla<sub>VIM-2</sub> (IncW)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7), 3 kb (aacA7, bla<sub>VIM-2</sub>, aacC1, aacA4)</td></tr><tr><td>10-1925</td><td>Kentucky</td><td>-</td><td>bla<sub>VIM-2</sub> (IncW)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7), 3 kb (aacA7, bla<sub>VIM-2</sub>, aacC1, aacA4)</td></tr><tr><td>10-1926</td><td>Kentucky</td><td>-</td><td>bla<sub>VIM-2</sub> (IncW)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>-</td><td>-</td><td>1.5 kb (aacA5, aadA7), 3 kb (aacA7, bla<sub>VIM-2</sub>, aacC1, aacA4)</td></tr><tr><td colspan="9">Isolates recovered from a single patient<sup>‡</sup></td></tr><tr><td>09-7981</td><td>Saintpaul</td><td>-</td><td>bla<sub>OXA-48</sub> (IncL/M, 70 kb)</td><td>WT</td><td>WT</td><td>-</td><td>-</td><td>-</td></tr><tr><td>10-0305</td><td>Kentucky</td><td>-</td><td>-</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>mph(A) (NT)</td><td>-</td><td>1.8 kb (dfrA12, aadA2)</td></tr><tr><td>11-0664</td><td>Kentucky</td><td>-</td><td>bla<sub>OXA-48</sub> (NT)</td><td>Ser83Phe, Asp87Gly</td><td>Ser80Ile</td><td>mph(A) (NT)</td><td>-</td><td>-</td></tr></tbody></table>

NT, not transferable; UT, untypeable

‡Isolate 09-9322 recovered by the French national surveillance system was also isolated from this single patient who had travelled to Egypt.
521
522
523
524
525
526
527
528
529
530

<figure><img src="image_2.png" /><figcaption>Figure 1. Human *S. enterica* serotype Kentucky isolates identified at the French National Reference Centre for *Salmonella* between 2000 and 2011</figcaption></figure>

The total annual number of *S. enterica* serotype Kentucky isolates is indicated by a black
triangle. The annual number of these isolates resistant to ciprofloxacin (CIP-R) is indicated
in red, and that of isolates resistant to extended-spectrum cephalosporins (ESC-R) is shown
in green. During this period, the total number of *Salmonella* spp. registered at the French
National Reference Centre was 128,836 (2000, *n*=12,883; 2001, *n*=12,601; 2002, *n*=11,775;
2003, *n*=10,472; 2004, *n*=10,589; 2005, *n*=11,439; 2006, *n*=10,154; 2007, *n*=8,124; 2008,
*n*=10,378; 2009, *n*=9,947; 2010, *n*=9,405; 2011, *n*=11,069).