JAC Advance Access originally published online on September 5, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):956-964; doi:10.1093/jac/dkm319
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Incidence of class A extended-spectrum ß-lactamases in Champagne-Ardenne (France): a 1 year prospective study
1 Laboratoire de Bactériologie-Virologie-Hygiène CHU de Reims, UFR Médecine Université Reims Champagne-Ardenne, 51092 Reims, France 2 Service de Bactériologie-Virologie, Hôpital de Bicêtre Faculté de Médecine Paris-Sud, Université Paris XI, 94275 K. Bicêtre, France 3 Centre Hospitalier de Manchester, Laboratoire, 41 avenue de Manchester, 08011 Charleville-Mézières, France 4 Centre Hospitalier de Chaumont, Laboratoire, 2 rue Jeanne d'Arc, 52000 Chaumont, France 5 Chalons en Champagne, Laboratoire, 51 rue du Commandant Derrien, 51000 Chalons en Champagne, France 6 Centre Hospitalier de Saint Dizier, Laboratoire, rue Godard Jeanson, 52100 Saint Dizier, France 7 Centre Hospitalier de Soissons, Laboratoire, 46 rue du Général de Gaulle, 02209 Soissons, France; 8 Centre Hospitalier de Troyes, Laboratoire de Microbiologie, 101 rue Anatole France, 10000 Troyes, France 9 Centre Hospitalier Auban Moët, Laboratoire, 137 rue de l'Hôpital, 51205 Epernay, France 10 Centre Hospitalier de Langres, Laboratoire, 52206 Langres, France 11 Laboratoire Gillard, 27 rue du Clou dans le fer, 51100 Reims, France 12 Laboratoire Leulier, 79 rue de Courlancy, 51100 Reims, France
* Corresponding author. Tel: +33-326-787-702; Fax: +33-326-784-134; E-mail: cdechamps{at}chu-reims.fr
Received 6 March 2007; returned 27 April 2007; revised 7 June 2007; accepted 27 July 2007
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Abstract |
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Objectives: To assess the frequency and diversity of extended spectrum ß-lactamases (ESBLs) in the Champagne-Ardenne region France, and to identify genetic elements associated with the blaCTX-M genes.
Methods: During 2004, all the non-duplicate isolates of Pseudomonas aeruginosa and Acinetobacter baumannii resistant to ceftazidime and of Enterobacteriaceae intermediate or resistant to ceftazidime and/or cefotaxime, screening samples excluded, were collected in 10 public hospitals and 3 private clinics. bla genes were sequenced and blaCTX-M environment characterized by PCR mapping.
Results: In Enterobacteriaceae (138/21 861; 0.6%), ESBLs were predominantly TEM-24 (n = 52; 37.7%) and CTX-M-15 (n = 37; 26.8%). Three new enzymes were identified, CTX-M-61 (CTX-M-1 group), TEM- and SHV-type. A. baumannii (n = 5) produced VEB-1 and P. aeruginosa (n = 2) SHV-2a. ISEcp1 was detected in 22/27 strains, disrupted in 7 of them. The IS903-like element was downstream of blaCTX-M-14 and blaCTX-M-16. ISCR1 was found upstream of blaCTX-M-2 and blaCTX-M-9, and ISCR1 and blaCTX-M-2 were located on a sul1-type class 1 integron. In comparison with 2001–02, ESBL distribution among Enterobacteriaceae showed an increase in CTX-M-type (44.9% vs 3.7% P < 10–7) due to Escherichia coli CTX-M-15 and to the almost total disappearance of TEM-3 (0.9% vs 51.2%). E. coli was the most frequent species (50.0% vs 5.1% in 1998) despite a similar prevalence to that in 1998 (0.5% vs 0.2%).
Conclusions: A careful detection of blaCTX-M-type spread to other species would help to anticipate clonal endemics such as those observed in Enterobacter aerogenes TEM-24.
Keywords: ESBLs , Enterobacteriaceae , Pseudomonas aeruginosa , Acinetobacter baumannii , insertion sequences
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Introduction |
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Since the 1980s extended-spectrum ß-lactamases (ESBLs) related to TEM- and SHV-type enzymes have been widely observed, mostly in Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae and more rarely in Escherichia coli.1,2
The numerous amino acid substitutions that occurred led to a great diversity of TEM-type (more than 150) and SHV-type (more than 85) enzymes. In the early 2000s, new non-TEM non-SHV ESBLs (CTX-M, PER-1 and VEB-1) were reported in epidemic clones of Enterobacteriaceae involved in hospital-acquired outbreaks in South America, Asia and particularly in Turkey and Eastern Europe.3–10
Before 2000, these new types had rarely been identified in France.7,11 Thereafter, whereas most of the TEM- or SHV-type-producing strains were hospital-acquired, the CTX-M types were chiefly community-acquired,12 thus making the spread of these ESBLs more difficult to control. The reservoir of most blaCTX-M was identified as Kluyvera spp.13 An ISEcp1-like insertion sequence was identified upstream of the blaCTX-M genes, associated with four out of the five blaCTX-M clusters (CTX-M-1, M-2, M-9 and M-25) with variations in the intergenic sequences upstream and downstream of the blaCTX-M genes.14,15 Among these genes, blaCTX-M-2, blaCTX-M-9 and blaCTX-M-20 were sometimes linked to ISCR1, a sequence-type termed ‘common region’ (CR) that is often found beyond but close to the 3' conserved sequences of class 1 integrons.16 These CRs resemble an atypical class of insertion sequences designated IS91-like.17 ISCR1 accommodates a transposase gene, Orf513.
The aim of this study was to assess the frequency and diversity of ESBLs produced by strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii in the Champagne-Ardenne region in eastern France, to detect epidemic clonal strains and to explore the insertion sequences associated with blaCTX-M.
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Materials and methods |
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Selection of clinical isolates
The Champagne-Ardenne region has a population of 1.34 million. The survey was conducted in the University hospital, the nine largest non-teaching public hospitals in the region and three private clinics from 1 January to 31 December 2004.
All the non-duplicate isolates of P. aeruginosa and A. baumannii resistant to ceftazidime (MIC > 32 mg/L) and of Enterobacteriaceae intermediate or resistant to ceftazidime and/or cefotaxime (MICs > 4 mg/L) and/or aminoglycosides with an AAC(6') I phenotype intermediate or resistant to amikacin (MIC > 8 mg/L), kanamycin (MIC > 8 mg/L) and tobramycin (MIC > 4 mg/L) were collected and sent every 3 months to the Reims hospital laboratory. All isolates from inpatients and outpatients were included, irrespective of where they were sampled or of their implication in infection. Screening samples, such as anal swabs, were excluded. For infections to be defined as hospital-acquired, they had to occur at least 48 h after admission during a stay within the survey period. Every 4 months, two strains, some of them producing an ESBL, were sent to each laboratory as quality controls.
Identification, susceptibility testing and confirmation of ESBL detection
Identification of the strains was verified by Rapid ID 32 E for Enterobacteriaceae and ID 32 GN for P. aeruginosa and A. baumannii (bioMérieux, Marcy l'Étoile, France) and antibiotic susceptibilities were determined by the disc diffusion method according to the recommendations of the Antibiogram Committee of the French Society for Microbiology (http://www.sfm.asso.fr/). Strains were screened for ESBL by the double-disc synergy test18 and with discs containing 30 µg of cefotaxime or ceftazidime alone and in combination with 10 µg of clavulanate (CDO2 and CDO3, Oxoid SA 69571 Dardilly France) onto Mueller–Hinton agar with and without 200 mg/L cloxacillin. Isoelectric focusing (IEF) was carried out for all the isolates ESBL-positive with these tests.
IEF assay and ESBL identification
ß-Lactamases were prepared by sonication from culture in Trypticase soy broth using a Vibra cell 72412 (Fisher Bioblock Scientific, BP 50111, 67403 Illkirch cedex, France). Analytical IEF was performed in 6% polyacrylamide gels containing ampholines with a pH range of 3.5–10. Proteins were focused at a constant temperature (6°C) for 1.5 h at 1 W of constant power per centimetre with a Multiphor II flatbed Electrophoresis Unit and EPS 3501 XL Power Supply (Amersham Biosciences, Saclay, 91898 Orsay Cedex, France). ß-Lactamase activity was revealed with iodine agar by overlaying the polyacrylamide gel with an agar gel containing 0.6% (w/v) penicillin G, 6% (w/v) potassium iodide and 0.6% (w/v) iodine. ß-Lactamases with known pIs were used as standards: TEM-1, pI 5.4; PSE-1 (CARB-2), pI 5.7; TEM-3, pI 6.3; TEM-24, pI 6.5; CTX-M-16, pI 8.2; and CTX-M-15, pI 8.6.6
Genes blaTEM, blaSHV, blaCTX-M and blaOXA were detected by PCR using specific primers as previously described for all the ESBL-producing strains (Table 1).3,4,6,10,19–22 The sequences were determined by direct sequencing of PCR products, performed by the dideoxy chain termination procedure of Sanger et al.23 on an Applied Biosystems 3730 XL DNA analyser using the BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems, Foster City, CA, USA). PCR and sequencing were performed for all ESBL-producing strains, but for Enterobacter aerogenes isolates producing an ESBL of pI 6.5 they were performed for one strain of each antibiotic-associated resistance phenotype. When sequencing was not performed enzymes were designated TEM-24-like.
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RAPD typing
The isolates were genotyped by RAPD to study their clonal diversity using RAPD analysis primer 2 [5'-d(GTTTCGCTCC)-3'], RAPD analysis primer 3 [5'-d(GTAGACCCGT)-3'], RAPD analysis primer 4 [5'-d(AAGAGCCCGT)-3'], RAPD analysis primer 5 [5'-d(AACGCGCAAC)-3'] and RAPD analysis primer 6 [5'-d(CCCGTCAGCA)-3'] from the Ready to Go RAPD analysis kit according to the manufacturer's instructions (Amersham Biosciences).
Genetic environment of blaCTX-M genes
To investigate the genetic structures at the origin of blaCTX-M gene acquisition, the genetic environment of blaCTX-M was characterized by PCR with the primers listed in Table 1. Whole-cell DNA of isolates was extracted as described previously.24 As blaCTX-M genes have often been reported in class 1 integrons downstream of a common region ISCR1 associated with Orf513 or downstream of an insertion sequence ISEcp1, the regions upstream of blaCTX-M genes were amplified with forward primers hybridizing to the insertion sequences ISEcp1, to the region Orf513 and the blaCTX-M reverse primer (CTX-MA2).13 The genetic sequences located downstream of different blaCTX-M genes were studied by PCR experiments with the forward primer CTX-MA1 and the reverse primer CTX-M-preB or IS903Bint (Table 1). When Orf513 was found upstream of blaCTX-M, a PCR experiment was performed with primer CTX-MA1 and reverse primer qacED1B to search for a sul1-type integron structure as previously described.13,25
The prevalence of ESBLs was calculated using the number of non-duplicate isolates in each species and each centre. The 
2 test was used to compare distributions with previous reports.7–11
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Results |
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Selection of clinical isolates
A total of 21 861 isolates of Enterobacteriaceae, 2345 P. aeruginosa and 186 A. baumannii were identified. Of the 504 resistant isolates included in the study, 138 Enterobacteriaceae (0.6% of the 21 861), 5 A. baumannii (2.7% of the 186) and 2 P. aeruginosa (0.08% of the 2345 isolates) produced an ESBL. They were isolated from urine (n = 115), respiratory tract samples (n = 13), blood cultures (n = 8), wounds (n = 7) and catheters (n = 2). Among Enterobacteriaceae, the most frequent species were E. coli (n = 69) and E. aerogenes (n = 50). The prevalence of ESBL production in each Enterobacteriaceae species taken separately was 14.7% for E. aerogenes, 1.0% for E. cloacae, 0.6% for K. pneumoniae, 0.5% for E. coli, 0.3% for Citrobacter koseri and 0.1% for Proteus mirabilis.
ESBL production and antimicrobial susceptibilities of the ESBL-producing strains
The ESBLs produced were TEM-type (n = 64), CTX-M-type (n = 62), SHV-type (n = 13) and VEB-1 (n = 6). The rates of ESBL-producing bacteria and enzyme-type distribution varied according to centres, mainly because of A. baumannii VEB-1, E. aerogenes TEM-24 and E. coli CTX-M-15 outbreaks (Table 2). Most ESBLs were CTX-M-type (16/23, 69.6%) in centre C and TEM-type (29/37, 78.4%) in centre B. Isolates acquired during a hospital stay (n = 72: 49.7%) were more often observed among TEM- (n = 44: 68.6%) and VEB-type (n = 5: 83.3%) than among CTX-M- (n = 19: 30.6%) and SHV-type (n = 4: 30.8%). In Enterobacteriaceae, they were more often resistant to ciprofloxacin (57/66, 86.4% versus 51/72, 70.8%; P = 0.02) and to amikacin (42/66, 63.6% versus 31/72, 43.1%; P = 0.02) than isolates present at admission or in outpatients. This was not the case for gentamicin (16/66, 22.2% versus 22/72, 30.6%), tobramycin (50/66, 75.8% versus 44/72, 61.1%) and co-trimoxazole (44/66, 66.7% versus 47/72, 65.3%) (Table 2). Resistances were less frequent in CTX-M-producing strains than in the other strains for tobramycin (26/62, 41.9% versus 68/76, 89.5%; P < 10–7), amikacin (17/62, 27.4% versus 56/76, 73.7%; P = 10–7) and co-trimoxazole (28/62, 45.2% versus 63/76, 82.9%; P = 3 x 10–6) (Table 3). But there was no significant difference regarding gentamicin (16/62, 25.8% versus 22/76, 28.9%) and quinolones (51/62, 82.3% versus 75/83, 90.4%). However, among the 37 CTX-M-15-producing isolates, all were resistant to ciprofloxacin, 14 (37.7%) to gentamicin, 16 (43.3%) to amikacin and 23 (62.2%) to tobramycin. In contrast, 6/37 (16.2%) of them were resistant to co-trimoxazole versus 22/25 (88.0%) of the other CTX-M-type-producing Enterobacteriaceae (P = 3 x 10–8).
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ESBL identification
Of the TEM-type ESBLs (n = 64), 52 were TEM-24-like enzymes, mostly from E. aerogenes (n = 50, 96.1%) and also from E. cloacae (n = 1) and E. coli (n = 1). No other ESBL was observed in E. aerogenes. The other TEM-type enzymes (n = 12) were TEM-52 (n = 5), TEM-22 (n = 2), TEM-21 (n = 1) and a new TEM (n = 1) from E. coli, TEM-21 (n = 2) from P. mirabilis and TEM-3 (n = 1) from C. koseri. The new TEM differed from TEM-133 by an F21L substitution.26 Genotype patterns of E. aerogenes TEM-24 (n = 50) were identical for all of the isolates. Among the CTX-M-type (n = 62), 91.9% were observed in E. coli (n = 57), which produced CTX-M-15 (n = 36), CTX-M-1 (n = 9), CTX-M-14 (n = 5), CTX-M-2 (n = 4), CTX-M-61 (n = 2) and CTX-M-16 (n = 1). There had been no previous report of CTX-M-61 belonging to the CTX-M-1 phylogenic group. CTX-M-61 was first observed in this study as a CTX-M-1-like enzyme, then extensively characterized in Salmonella Typhimurium isolated in Reims in 2005 (accession no. EF219142). The other CTX-M-producing isolates were K. pneumoniae that produced CTX-M-14 (n = 3) and CTX-M-15 (n = 1), and one E. cloacae CTX-M-9 (n = 1). CTX-M-15 E. coli isolates, identified in centres A, C, D, E, H, I and J, harboured 11 different genotypes (Table 2). Three of them were isolated in several centres; V in centres A, C, E and H, III in centres A and J of the same city and IV in centres A and D. In centre C, it was related to the admission of patients from the same long-stay care unit.
SHV-type enzymes (n = 13) were SHV-12 from E. cloacae (n = 4), E. coli (n = 2), K. pneumoniae (n = 1) and C. freundii (n = 1); SHV-2 (n = 1), SHV-5 (n = 1) and new SHV from K. pneumoniae (n = 1); and SHV2a from P. aeruginosa (n = 2). The new SHV differed from SHV-1 by a D214G substitution. One non-TEM-, non-SHV-type enzyme, VEB-1 (n = 6) was produced by A. baumannii (n = 5) and Enterobacter sakazakii (n = 1). VEB-1-producing A. baumannii isolates had the same genotype and were responsible for an outbreak in three hospitals.27
Genetic environment of blaCTX-M genes
The genetic environment of the blaCTX-M gene was studied for 27 strains producing CTX-M-1 (n = 7), CTX-M-2 (n = 4), CTX-M-9 (n = 1), CTX-M-14 (n = 3), CTX-M-15 (n = 11) and CTX-M-16 (n = 1) with different resistance phenotypes, and/or RAPD patterns. Insertion sequence ISEcp1 was identified upstream of blaCTX-M genes in 22 strains (Figure 1). In four strains (GI4014, EY4012, SD4014 and TR4095), PCR amplification was obtained with ISEcp1 prom+ primer but not with ISEcp1A primer, suggesting the presence of the disrupted IS element. These DNA sequences contained a putative promoter region probably involved in the transcription of downstream-located blaCTX-M genes.14 The right boundary of ISEcp1 was located between 43 and 80 bp upstream of the start codon of blaCTX-M genes. ISEcp1 was identified at 80 bp upstream of blaCTX-M-1 genes and at 48 bp (W sequence) upstream of blaCTX-M-15 genes (Figure 1). The 48 bp shared 100% nucleotide identity with the 48 bp upstream of blaCTX-M-1 genes. The distance between ISEcp1 and the start codon of blaCTX-M-9-like (blaCTX-M-14 and blaCTX-M-16) genes was identical at 43 bp (Figure 1). Downstream of blaCTX-M-9-like genes, an IS903-like element was found. ISEcp1 was not identified upstream of blaCTX-M-2 and blaCTX-M-9 genes. Consequently, the ISCR1 was sought and found in all the strains harbouring those genes. However, the collinearity between ISCR1 and blaCTX-M-2 was found only in one strain, RS4076. This blaCTX-M-2 gene was located in a sul1-type class 1 integron.
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Discussion |
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Before 2004, a progressive increase in the prevalence of CTX-M-type enzymes was observed in different areas in France,11,28,29 but in our region no information was available. To compare data between different surveys, the MIC and specimen criteria for isolate inclusion were the same as previously reported.7,11 Some ESBL-producing isolates with both cefotaxime and ceftazidime MICs
4 mg/L may have been missed. This has been reported for some TEM- or SHV-type-producing P. mirabilis and K. pneumoniae but not for CTX-M-type-producing strains.30,31 To avoid misdetection of ESBL masked by Ambler class C cephalosporinase, synergy tests were repeated on Mueller–Hinton agar containing 200 mg/L cloxacillin. The prevalence of ESBL production in Enterobacteriaceae isolated during our survey (0.6%) was lower than in the French data obtained in 1998 (3.2%; P < 10–7) but similar to those obtained in 2001–02 (0.8%).7,11,28 In comparison with the Auvergne 2001–02 and Nîmes distribution of the ESBLs among Enterobacteriaceae,11,29 our survey underlines the increase in CTX-M-type (44.9% versus 3.7% and 10.0%; P < 10–7), linked to E. coli expansion, as reported around the world.4,8,12,21,24,32,33 In this species, CTX-M types (82.8% ESBL), more frequent than in previous studies,29,32 were mainly CTX-M-15 (52.2% ESBL and 63% CTX-M-type) probably due to a plasmid and a clonal E. coli dissemination.33 A decrease in TEM-type (46.4% versus 95.0% and 90.0% in Auvergne and Nîmes; P < 10–7), with the disappearance of most TEM-3 (0.9% versus 51.2% and 42.5%) and an increase in SHV (8.0% versus 1.3% and 0.0%; P = 0.001) were observed (Table 4) as reported in Paris hospitals in 2002, earlier than in other French areas.11,28,29 SHV-type enzymes have rarely been reported in P. aeruginosa, but SHV-2a has been observed in France.34 Inter-hospital transmission of isolates has been previously reported for E. aerogenes TEM-24 and A. baumannii VEB-1. In our survey, these strains had the same genotype pattern as the clonal strains previously reported mainly in northern France in 2003–04.7,12,27 The index case of A. baumannii VEB-1 in centre A was one patient transferred from centre B in 2003. In our region, the epidemic was efficiently controlled by hygiene measures and no case was identified after 2004.
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Repeated admission of patients from geriatric centres, such as 15 isolates of E. coli CTX-M-15 in centre C, can be a source of nosocomial CTX-M-type E. coli.35 The presence of three epidemic genotypes (III, IV and V) in centre A can be explained by its role as a tertiary hospital admitting patients from the other centres.
In early reports, ESBLs were very often associated with aminoglycoside and quinolone resistances.2 Associated resistances have been less frequently reported among patients in the community,12 as observed in our study on ciprofloxacin and amikacin resistance. The high frequency of the combination of ciprofloxacin resistance32 with CTX-M-15 enzyme that was more frequent in nosocomial isolates, and conversely the high frequency of co-trimoxazole resistance in other CTX-M-type enzymes isolates from the community showed that associated resistance in ESBL producers may depend on the antibiotics used, respectively, in hospitals and in the community.
blaCTX-M genes have often been reported downstream of an insertion sequence ISEcp1 or in complex class 1 integrons downstream of a common region ISCR1 and associated with Orf513. ISCR1 is mainly associated with blaCTX-M-2, blaCTX-M-9 and blaCTX-M-20 genes.16,17 In three CTX-M-2 isolates and one CTX-M-9 isolate in our study, the association was suggested by PCR results, but collinearity was not found. This suggests that either ISCR1 was not linked to blaCTX-M or that the blaCTX-M gene was not in a class 1 integron. Several blaCTX-M have been reported, bracketed by an ISEcp1-like element upstream and an IS903-like element downstream such as blaCTX-M-14.25 The role of the IS903-like element is not fully understood.15 The present report is the first to identify the genetic environment of the blaCTX-M-16 gene, which combines a disrupted ISEcp1 upstream, as in some CTX-M-1- and CTX-M-15-producing strains, a Y sequence between ISEcp1 and blaCTX-M and IS903 downstream of blaCTX-M as blaCTX-M-14. These two enzymes belong to the same blaCTX-M-9 group, and our results are consistent with the hypothesis of the same progenitor.3,21 The variability in ISEcp1 size for the same CTX-M enzyme gene illustrates the circulation of sporadic strains among clonal strains. Taken together these results provide strong evidence that ISEcp1 plays a major role in the spread and expression of blaCTX-M genes in Enterobacteriaceae.
Previously ESBL-producing strains were mainly nosocomial.2,7,11 The emergence of ESBL isolates in the community, mainly due to CTX-M other than CTX-M-15, is an additional problem for the control of nosocomial ESBL-producing strains.
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This work was supported by grants from Centre Hospitalier Régional Universitaire de Reims, France, and Ministère de la Santé et des Solidarités France (Projet Hospitalier de Recherche Clinique).
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None to declare.
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Acknowledgements |
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We thank Jeffrey Watts for his revision of the manuscript.
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References |
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1 Sirot D, Sirot J, Labia R, et al. Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel ß-lactamase. J Antimicrob Chemother (1987) 20:323–34.
2
De Champs C, Sirot D, Chanal C, et al. Concomitant dissemination of three extended-spectrum ß-lactamases among different Enterobacteriaceae isolated in a French hospital. J Antimicrob Chemother (1991) 27:441–57.
3
Bonnet R, Dutour C, Sampaio JLM, et al. Novel cefotaximase (CTX-M-16) with increased catalytic efficiency due to substitution Asp-240 
Gly. Antimicrob Agents Chemother (2001) 45:2269–75.
4
Cao V, Lambert T, Nhu DQ, et al. Distribution of extended-spectrum ß-lactamases in clinical isolates of Enterobacteriaceae in Vietnam. Antimicrob Agents Chemother (2002) 46:3739–43.
5
Casin I, Hanau-Berçot I, Podglajen H, et al. Salmonella enterica serovar Typhimurium blaPER-1-carrying plasmid pSTI1 encodes an extended-spectrum aminoglycoside 6'-N-acetyltransferase of type Ib. Antimicrob Agents Chemother (2003) 47:697–703.
6
De Champs C, Poirel L, Bonnet R, et al. Prospective survey of ß-lactamases produced by ceftazidime-resistant Pseudomonas aeruginosa isolated in a French hospital in 2000. Antimicrob Agents Chemother (2002) 46:3031–4.
7
De Champs C, Sirot D, Chanal C, et al. A 1998 survey of extended-spectrum ß-lactamases in Enterobacteriaceae in France. Antimicrob Agents Chemother (2000) 44:3177–9.
8
Gniadkowski M, Schneider I, Palucha A, et al. Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw, Poland: identification of a new CTX-M-3 cefotaxime-hydrolyzing ß-lactamase that is closely related to the CTX-M-1/MEN-1 enzyme. Antimicrob Agents Chemother (1998) 42:827–32.
9 Vahaboglu H, Öztürk R, Aygün G, et al. Widespread detection of PER-1-type extended-spectrum ß-lactamases among nosocomial Acinetobacter and Pseudomonas aeruginosa isolates in Turkey: a nationwide multicentre study. Antimicrob Agents Chemother (1997) 41:2265–9.[Abstract]
10
Girlich D, Poirel L, Leelaporn A, et al. Molecular epidemiology of the integron-located VEB-1 extended-spectrum ß-lactamase in nosocomial enterobacterial isolates in Bangkok, Thailand. J Clin Microbiol (2001) 39:175–82.
11
De Champs C, Chanal C, Sirot D, et al. Frequency and diversity of class A extended-spectrum ß-lactamases in hospitals of the Auvergne, France: a 2 year prospective study. J Antimicrob Chemother (2004) 54:634–9.
12
Valverde A, Coque TM, Sanchez-Moreno MP, et al. Dramatic increase in prevalence of fecal carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae during nonoutbreak situations in Spain. J Clin Microbiol (2004) 42:4769–75.
13 Saladin M, Cao VT, Lambert T, et al. Diversity of CTX-M ß-lactamases and their promoter regions from Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol Lett (2002) 209:161–8.[Web of Science][Medline]
14
Poirel L, Decousser JW, Nordmann P. Insertion sequence ISEcp1B is involved in expression and mobilization of a blaCTX-M ß-lactamase gene. Antimicrob Agents Chemother (2003) 47:2938–45.
15
Poirel L, Lartigue MF, Decousser JW, et al. ISEcp1B-mediated transposition of a blaCTX-M ß-lactamase gene. Antimicrob Agents Chemother (2005) 49:447–50.
16
Toleman MA, Bennett PM, Walsh TR. Common regions e.g. orf513 and antibiotic resistance: IS91-like elements evolving complex class 1 integrons. J Antimicrob Chemother (2006) 58:1–6.
17
Toleman MA, Bennett PM, Walsh TR. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev (2006) 70:296–316.
18 Sirot J. Detection of extended-spectrum plasmid-mediated ß-lactamases by disc diffusion. Clin Microbiol Infect (1996) 2(Suppl 1):35–9.
19 Mabilat C, Goussard S, Sougakoff W, et al. Direct sequencing of the amplified structural gene and promoter for the extended-broad-spectrum ß-lactamase TEM-9 (RHH-1) of Klebsiella pneumoniae. Plasmid (1990) 23:27–34.[CrossRef][Web of Science][Medline]
20
Dutour C, Bonnet R, Marchandin H, et al. CTX-M-1, CTX-M-3, and CTX-M-14- ß-lactamases from Enterobacteriaceae isolated in France. Antimicrob Agents Chemother (2002) 46:534–7.
21
Chanawong A, M'Zali FH, Heritage J, et al. Three cefotaximases, CTX-M-9, CTX-M-13, and CTX-M-14, among Enterobacteriaceae in the People's Republic of China. Antimicrob Agents Chemother (2002) 46:630–7.
22 Naas T, Poirel L, Karim A, et al. Molecular characterization of In50, a class 1 integron encoding the gene for the extended-spectrum ß-lactamase VEB-1 in Pseudomonas aeruginosa. FEMS Microbiol Lett (1999) 176:411–9.[Web of Science][Medline]
23
Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA (1977) 74:5463–7.
24 Karim A, Poirel L, Nagarajan S, et al. Plasmid-mediated extended-spectrum ß-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett (2001) 201:237–41.[Web of Science][Medline]
25 Lartigue MF, Poirel L, Nordmann P. Diversity of genetic environment of blaCTX-M genes. FEMS Microbiol Lett (2004) 234:201–7.[CrossRef][Web of Science][Medline]
26
Hernández JR, Martínez-Martínez L, Cantón R, et al. Nationwide study of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum ß-lactamases in Spain. Antimicrob Agents Chemother (2005) 49:2122–5.
27 Naas T, Coignard B, Carbonne A, et al. VEB-1 extended-spectrum ß-lactamase-producing Acinetobacter baumannii, France. Emerg Infect Dis (2006) 12:1214–22.[Web of Science][Medline]
28 Lartigue MF, Fortineau N, Nordmann P. Spread of novel expanded-spectrum ß-lactamases in Enterobacteriaceae in a university hospital in the Paris area, France. Clin Microbiol Infect (2005) 11:588–91.[CrossRef][Web of Science][Medline]
29
Lavigne JP, Bouziges N, Chanal C, et al. Molecular epidemiology of Enterobacteriaceae isolates producing extended-spectrum ß-lactamases in a French hospital. J Clin Microbiol (2004) 42:3805–8.
30
Bonnet R, De Champs C, Sirot D, et al. Diversity of TEM mutants in Proteus mirabilis. Antimicrob Agents Chemother (1999) 43:2671–7.
31
Tofteland S, Haldorsen B, Dahl KH, et al. Effects of phenotype and genotype on methods for detection of extended-spectrum-ß-lactamase-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in Norway. J Clin Microbiol (2007) 45:199–205.
32
Lavigne JP, Marchandin H, Delmas J, et al. qnrA in CTX-M-producing Escherichia coli isolates from France. Antimicrob Agents Chemother (2006) 50:4224–8.
33
Lavollay M, Mamlouk K, Frank T, et al. Clonal dissemination of a CTX-M-15 ß-lactamase-producing Escherichia coli strain in the Paris area, Tunis, and Bangui. Antimicrob Agents Chemother (2006) 50:2433–8.
34
Naas T, Philippon L, Poirel L, et al. An SHV-derived extended-spectrum-ß-lactamase in Pseudomonas aeruginosa. Antimicrob Agents Chemother (1999) 43:1281–4.
35
Leflon-Guibout V, Jurand C, Bonacorsi S, et al. Emergence and spread of three clonally related virulent isolates of CTX-M-15-producing Escherichia coli with variable resistance to aminoglycosides and tetracycline in a French geriatric hospital. Antimicrob Agents Chemother (2004) 48:3736–42.
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