Abstract
Our goal was to determine the characteristics and the mode of acquisition of healthcare-associated bacteraemia due to CTX-M-producing Escherichia coli in a 1,800-bed hospital. Sixteen extended-spectrum β-lactamase (ESBL)-producing E. coli strains were collected between 2001 and 2006 from patients with bloodstream infections. The incidence density of these infections increased from 0.002 to 0.02 per 1,000 days of hospitalisation during the study period. Most of the strains (87%) produced a CTX-M-type enzyme associated with TEM-1 (86%), OXA-30 (50%), AAC(3)-II (57%), AAC(6′) (50%) and QnrS1 (7%). When present (n = 8), the bla CTX-M-15 gene was always located downstream of the insertion sequence ISEcp1. Co-resistance was generally observed: fluoroquinolones (81%), trimethoprim-sulfamethoxazole (62%) and/or aminoglycosides (69%). Although the strains were found to be genetically unrelated, most of the cases were hospital-acquired (69%) or healthcare-associated (25%), underlining the need for infection control measures to limit the spread of ESBL-producing E. coli in hospital settings.
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Introduction
The first two CTX-M-type extended-spectrum β-lactamases (ESBLs) were isolated in 1989 in Europe and in Argentina respectively [1, 2]. The number of CTX-M-type variants described has increased steadily since 1995 [3]. Since the early 2000s, CTX-M-type enzymes have spread worldwide among Escherichia coli strains [4, 5] and the threat of severe infections such as bloodstream infections caused by ESBL-producing E. coli have become a reality [6]. When bacteraemia is caused by ESBL producers, there is a delay in initiating an appropriate antibiotic treatment and high mortality rates are reported [6, 7]. Indeed, CTX-M production is frequently associated with resistance to fluoroquinolones [6–10], and empirical treatment by third-generation cephalosporins or fluoroquinolones, two groups of antibiotics often used for bloodstream infections suspected of being caused by E. coli, is inadequate in this context. Studies have shown that CTX-M-producing E. coli have spread in the community [11, 12], constituting a wide reservoir for these organisms. Since the circumstances and the consequences of the emergence of ESBL E. coli in severe infections are still not well understood, despite several studies [6, 7, 13, 14], this work was performed with the objective of analysing the clinical and epidemiological features of these infections over a period of 66 months, as well as the phenotypic, molecular and virulence aspects.
Materials and methods
Study design and patients
The study was conducted at Pitié-Salpêtrière (PS) hospital, Paris, France, a 1,800-bed teaching hospital that began to survey ESBL Enterobacteriaceae in the mid 1980s [15]. The LIS database of the Clinical Microbiology Laboratory was retrospectively analysed for the period January 2001 to June 2006 to identify patients who had had an episode of bacteraemia caused by a strain of E. coli with an ESBL-compatible pattern during their stay in PS hospital, i.e. with a positive double disk synergy test, a test that has been systematically applied since 1985 to each strain of enterobacteria in this laboratory [15, 16]. If several blood cultures from the same patient were positive for an E. coli strain with an ESBL-compatible pattern, the first isolate was selected for further study. Upon review of the patients’ records, the following data were collected: age, sex, hospital location, date of admission and length of stay in hospital, date of collection of positive specimen(s), primary site of infection, admission to any hospital during the previous year, use of an intravascular device, urinary catheter or mechanical ventilation before bacteraemia, previous antibiotherapy during the hospital stay, antibiotic treatment received for ESBL E. coli bacteraemia and outcome.
Nosocomial infection was defined as an infection that occurred >48 h after admission to the hospital in a patient with no sign of infection at admission. Bacteraemia that occurred within the first 48 h after admission was further classified as healthcare-associated if any of the following criteria were present: >48-h hospital admission during the previous 90 days, chronic haemodialysis, chronic treatment by intravenous medication or home wound care in the previous 30 days, or residence in a nursing home or long-term care facility. Otherwise, the cases were considered to be community-acquired [17].
Bacterial strains and susceptibility assays
The strains included were re-identified by the API 20E system (bioMérieux, Marcy l’Etoile, France) and susceptibility to antimicrobial agents was checked using the disk diffusion method and interpreted according to the guidelines of the Antibiogram Committee of the French Society for Microbiology (CA-SFM) (www.sfm.asso.fr). The double disk synergy test was performed on MH agar plates with disks of cefotaxime, ceftazidime, cefepime, aztreonam on one side and amoxicillin-clavulanic acid-containing disks on the other [16]. The synergy between cephalosporin and clavulanic acid was quantified using Etests CT/CTL and TZ/TZL (AB Biodisk, Solna, Sweden), combining cefotaxime or ceftazidime with clavulanate, performed on MH agar plates. The ESBL Etest was considered positive according to the manufacturer’s protocol.
Beta-lactamase characterisation and screening of resistance genes
The strains included were screened using the PCR primers given in Table 1 for the presence of the following β-lactamase genes: bla TEM, bla SHV, bla CTX-M, bla OXA-30, as well as other genes of resistance to fluoroquinolones, qnrA, qnrB and qnrS, and to aminoglycosides aac(3)II and aac(6′)-Ib. Amplicons were then sequenced using the Big Dye Terminator cycle sequencing ready reaction kit (Applied Biosystems, Foster City, CA, USA) in an ABI Prism 310 DNA sequencer (Applied Biosystems). The sequences obtained were compared with the sequences available (GeneBank).
Genetic environment of bla CTX-M-15
The genetic environment of bla CTX-M-15 was characterised by PCR with the primers listed in Table 1. The region located upstream of the bla CTX-M-15 gene was amplified with forward primers hybridising to the insertion sequence ISEcp1 and with the bla CTX-M reverse primer; amplicons were sequenced on both strands.
Molecular typing
The strains included were also evaluated for genetic relatedness using Pulsed-Field Gel Electrophoresis (PFGE) with Xba I (New England Biolabs, Ipswich, MA, USA) digestion of genomic DNA. DNA fragments were separated with a CHEF-DRII system (Biorad) through a 1% agarose gel in 0.5X Tris-borate-EDTA buffer. Conditions for migration were as follows: temperature, 14°C; voltage, 5V/cm; pulses, 5–40 s for 21 h. Gels were stained using ethidium bromide and photographed under UV illumination. Fingerprints were first interpreted visually, then with the Gelcompar software (Applied Maths, Sint-Martens-Latem, Belgium) according to the criteria suggested by Tenover et al. [18].
Phylogenetic grouping
The phylogenetic group was determined for each of the strains included with markers yjaA and chuA, and the DNA fragment TSPE4.C2 [19]. Those markers were screened by PCR as described above, with the primers listed in Table 1. The results were interpreted according to Clermont et al. [19].
Results
During the period January 2001 to June 2006, 18 episodes of bacteraemia caused by a strain of E. coli with an ESBL-compatible pattern were identified. ESBL production was confirmed by the double disk synergy test and by ESBL Etests for 16 of the 18 strains. For the 2 remaining strains, the result of the synergy test between β-lactam and clavulanate was not compatible with ESBL production when quantified using ESBL Etests. In these 2 strains, bla OXA-30, but no ESBL, was detected and the two corresponding episodes were subsequently excluded.
Overall, the 16 included cases represented 1.5% of E. coli bacteraemia episodes for the study period. However, this proportion increased from 0.4 to 4.3% between 2001 and the first semester of 2006, as shown in Fig. 1 (Chi-squared test for trend: 7.28, p=0.007). The incidence density of bacteraemia caused by ESBL-producing E. coli increased from 0.002 to 0.02 per 1,000 days of hospitalisation.
As shown in Table 2, the median age was 52 (range 26–69, mean 51.5 ± 11.1 years). Seven patients had been hospitalised at least once during the year before their stay in PS Hospital. The mean and the median of the duration of stay in PS hospital before the sampling of positive blood culture were 23 ± 30 and 10 days respectively. Before this sampling, the majority of the patients had stayed in the intensive care unit for at least 5 days (9 out of 16, 56%), had had at least one invasive procedure (13 out of 16, 81%), mainly a urinary catheter (n = 11), an intravascular device (n = 12) or mechanical ventilation (n = 6), or had received previous antibiotic therapy (11 out of 16, 69%), mainly third generation cephalosporin (n = 6) or fluoroquinolone (n = 8). The primary source of ESBL E. coli infection was established in 13 patients: urinary tract (n = 8), respiratory tract (n = 3), catheter-associated infection (n = 1), mediastinitis (n = 1) and infection of the ascitic fluid (n = 1). On the basis of the data collected, 11 out of the 16 cases were considered to be hospital-acquired, 4 as healthcare-associated and only 1 as community-acquired.
Five (31%) patients were empirically treated with imipenem shortly after sampling, but before the results of susceptibility tests. All but one patients were treated with imipenem after the diagnosis (the latter patient died before the results were available), in association with aminoglycosides in 13 cases. Three of the 16 patients (19%) died within 30 days of the diagnosis: 2 from septic shock and 1 from post-sternotomy mediastinitis. Death was directly attributed to ESBL E. coli bacteraemia in these three cases.
The results of susceptibility tests and content in ESBL-encoding genes for the 16 strains are shown in Table 3. A bla CTX-M gene was detected in 14 (87%) strains: either bla CTX-M-15 (n = 8), bla CTX-M-1 (n = 3), bla CTX-M-9 (n = 2) or bla CTX-M-14 (n = 1). The two remaining strains produced TEM-52. CTX-M-15 was always associated with another β-lactamase: OXA-30 and TEM-1 (n = 4), OXA-30 alone (n = 1), or TEM-1 alone (n = 3). Five of the six strains producing CTX-M-1, CTX-M-9 or CTX-M-14 also produced TEM-1 and OXA-30 (n = 2) or TEM-1 alone (n = 3). The two strains producing TEM-52 did not carry any other bla genes. The majority of the strains (13 out of 16) were resistant to fluoroquinolones, but only one carried a qnr gene, qnrS1 in a CTX-M-15-producing isolate. Almost all (11 out of 13) CTX-M-producing strains carried either both aac(3)-II and aac(6′)-Ib genes (4 CTX-M-15-, 1 CTX-M-1- and 1 CTX-M-9-producing strains) or aac(3)-II alone (1 CTX-M-9- and 1 CTX-M-14-producing strain). CTX-M-1, -9 and -14 were always associated with resistance to tetracycline and sulfonamides, whereas CTX-M-15 strains were mainly susceptible to both drugs or resistant to tetracycline alone.
The insertion sequence ISEcp1 was identified at 48 bp upstream of the bla CTX-M gene in all CTX-M-15-producing strains. In three strains (03-1, 06-4 and 06-5), PCR amplification was obtained with ISEcp1 PROM+ primer, but not with ISEcp1A primer, suggesting the presence of a disrupted IS element.
According to the criteria commonly used [18], the PFGE patterns obtained with the Xba I-restricted DNA were unrelated, even for the CTX-M-15-producing isolates (data not shown). Distribution into phylogenetic groups was as follows: 5 isolates belonged to each of the B23, D2 and A1 groups, whereas the last isolate belonged to the B1 group (Table 3). Concerning specifically the 8 CTX-M-15-producing strains, 4 belonged to group B23, 3 to group A1 and 1 to group D2. In contrast, only 1 of the 6 other CTX-M-producing strains belonged to the B23 group.
Discussion
Several recent studies have investigated ESBL E. coli bacteraemia, but this is the first study to focus on the emergence of ESBL-producing E. coli bloodstream infections in France, where they were virtually absent before 2000, as shown by national surveillance (www.onerba.org). At PS hospital, the largest teaching hospital in France, the yearly number of such infections increased from 1 case in 2001 to 5 cases in 2005, and 5 cases for the first semester of 2006, leading to a 10-fold increase in the proportion of ESBL strains among E. coli bacteraemia cases (from 0.4 to 4.3%), and in the incidence rate of ESBL E. coli bacteraemia cases (from 0.002 to 0.02 per 1,000 days of hospitalisation). This phenomenon has also been observed in southern Spain by Rodríguez-Baño et al., who reported an increase from 6 cases in 2001 to 16 cases in 2004 in a 950-bed teaching hospital [6]. The increase in infections due to ESBL E. coli in our hospital is consistent with the increasing proportion of strains resistant to third generation cephalosporins in E. coli bacteraemia cases assessed in France during the same period through the European Antibiotic Resistance Surveillance System (EARSS, www.rivm.nl/earss ), from <1 to 2% between 2002 and 2006. Despite a clear increase, the proportion of strains resistant to third generation cephalosporins among E. coli isolated from blood culture remained in 2006 markedly lower in our study than in other European countries, e.g. 8.8% in Spain in 2001–2005 and 13% in the UK in 2003–2005 [6, 7].
In our study, most of the strains (14 out of 16, 87%) produced a CTX-M-type ESBL, a rate somewhat higher than in other studies on ESBL E. coli bacteraemia during the same period: 70% in southern Spain and 37% in Italy [6, 9]. Moreover, the results of the two latter studies contrast with ours due to the fact that CTX-M-15 was absent in southern Spain or weakly represented in Rome (3%) among CTX-M-type ESBLs [6, 9]. The high proportion of CTX-M as a whole, and more precisely of CTX-M-15, we report here is consistent with the place of these emerging β-lactamases among ESBL E. coli isolated from clinical samples in France during the first half of 2000s, ranging between 40 and 76% [10, 20, 21]. CTX-M-15 differs from CTX-M-3 due to an Asp-240-Gly substitution that increases its catalytic efficiency against ceftazidime [22]. This feature likely confers an epidemiological advantage to CTX-M-15 in a hospital setting, where ceftazidime is largely used (www.esac.ua.ac.be).
Not surprisingly, almost all (13 out of 14) the CTX-M-producing E. coli carried at least one other β-lactamase-encoding gene, mainly TEM-1, OXA-30 or both. Half of the CTX-M-15-producing strains carried both genes, a combination already encountered in a single plasmid [23–25]. Our results also show high rates of co-resistance to potentially active drugs, e.g., fluoroquinolones (81%), trimethoprim-sulfamethoxazole (62%) and aminoglycosides (69%), as already found in other studies on ESBL E. coli bacteraemia [6–9, 20, 21]. In this study, the AAC(3)-II and AAC(6′) determinants were identified in half of the CTX-M-producing strains. However, only 3 of the 8 CTX-M-15-producing strains carried the combination of the four determinants OXA-30, TEM-1, AAC(3)-II and AAC(6′) that has been described in the 92-kb plasmid pC15-1a in association with the tetracycline resistance gene tetA [23], whereas the other strains exhibited three distinct combinations of these four genes, suggesting high genomic variability. As described in several studies, the bla CTX-M-15 gene was always located 48 bp downstream of the insertion sequence ISEcp1, which was disrupted in several strains [20, 23, 26–28].
Plasmid-mediated resistance to quinolones (qnrS1) was detected in only one CTX-M-15-producing strain (12%). The proportion of qnr-carrying strains in France was 8% of CTX-M E. coli in 2004, and 3.3% of ESBL-producing Enterobacteriaceae in 2004 [29, 30]. The qnr genes found in these two studies were all qnrA. The gene qnrS1 was found in some ESBL-producing Enterobacteriaceae in 2002–2005 in Paris, but always associated with CTX-M-1 [31]. The same gene has also been found in association with CTX-M-14, CTX-M-24 [32], CTX-M-9 and recently with CTX-M-15 in an Enterobacter cloacae isolate [33].
The primary sites of E. coli bacteraemia were mainly urinary tract infections (50%) in our study, as in a few others [6, 7], contrasting with other studies that reported lower proportions of this type of infection. These differences could be due to the different frequency of a urinary catheter in the study population, a major risk factor for UTI and bacteraemia [8, 9, 13, 14]. Pulmonary infections (19%) were the second most common primary sites of infections, similar to rates previously reported [8, 13], but higher than those in other studies reporting proportions of only 0–5% [6, 7, 9]. The high frequency of pulmonary infections in our study can be explained by the high frequency of mechanical ventilation (37%).
In our study, the median duration of stay in hospital before blood culture positive for ESBL E. coli was 10 days. Rodríguez-Baño et al. reported a median duration of stay of 26 days and found that a previous long hospital stay was a risk factor for ESBL-producing isolates in patients with nosocomial bacteraemia [34]. In our study, most patients (81%) had at least one invasive procedure, mainly insertion of urinary (69%) and intravascular catheters (56%), reported to be risk factors for ESBL-producing isolates in patients with bacteraemia [34, 35]. The majority of the patients included in our study (68%) had received previous antibiotic therapy before bacteraemia, mainly third generation cephalosporins (37%) or fluoroquinolones (50%), molecules found in other studies to be associated with ESBL-producing isolates in patients with bloodstream infections [13, 34–36]. ESBL-producing E. coli, more precisely CTX-M-producing strains, have often been described as community-acquired [11, 12]. In this study, we found that cases of bacteraemia with these organisms were rarely strictly community-acquired, and only 1 patient (6%) had neither a known previous stay in hospital nor any invasive procedures. This proportion of community-acquired bacteraemia cases among bacteraemia episodes due to ESBL-producing strains in our study is lower than those reported by Rodríguez-Baño et al. and Kang et al. (19% and 37% respectively) [6, 9, 14]. The other cases were either hospital-acquired (69%) or healthcare-associated (25%), showing the importance of hospital acquisition and invasive procedures in the occurrence of ESBL E. coli bacteraemia. Moreover, more than half of the patients were hospitalised in the ICU at the time of the positive blood culture, a rate higher than those reported in other studies [7, 8]. The mortality rate (19%) was similar to those reported elsewhere [6, 13, 14], but lower than that (61%) reported by Melzer et al. [7], who found a delay of at least 1 day before the appropriate antibiotic treatment was begun.
E. coli is divided into four main phylogenetic groups: A, B1, B2 and D [19, 37]. Virulent extra-intestinal strains mainly belong to the phylogenetic group B2, and, to a lesser extent, to group D [38], whereas commensal strains mainly belong to groups A or B1. In our study, only a third of the strains belonged to group B2, whereas another third belonged to group A. These results contrast with those reported in Tunisia, where 83% of ESBL E. coli isolated from blood culture belonged to the group B2 [39]. The discordance between the severity of the illness and the low-virulence groups can be explained by the iatrogenic origin of those bacteraemia episodes, since among the 6 cases that occurred due to a A or B1 strain, 2 had ventilator-associated pneumonia, 2 an iatrogenic urinary tract infection, 1 a catheter-associated infection, and the last one several invasive procedures.
Although mainly hospital-acquired, the 16 strains studied were unrelated on the basis of resistance patterns, phylogenetic groups and PFGE patterns, indicating a wide diversity. Therefore, clonal diffusion of one or few strains was not the cause of the nosocomial acquisition in our study, whereas outbreaks of clonally-related ESBL E. coli were reported in other healthcare facilities [23, 40].
In conclusion, ESBL-producing E. coli is an emerging cause of bloodstream infections in France, and involves mainly CTX-M-15. This emergence corresponds to a rapid change in the epidemiology of those infections. CTX-M-type enzymes have spread within the communities, favouring admission to hospitals of patients with severe community-acquired infections due to CTX-M-15-producing E. coli. However, our report demonstrates that these organisms are also causing severe hospital-acquired infections, and that infection control measures commonly applied to other multiple resistant organisms could contribute to limiting their spread into hospital settings.
References
Bernard H, Tancrede C, Livrelli V, Morand A, Barthelemy M, Labia R (1992) A novel plasmid-mediated extended-spectrum beta-lactamase not derived from TEM-or SHV-type enzymes. J Antimicrob Chemother 29(5):590–592
Bauernfeind A, Grimm H, Schweighart S (1990) A new plasmidic cefotaximase in a clinical isolate of Escherichia coli. Infection 18(5):294–298
Bonnet R (2004) Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48(1):1–14
Livermore DM, Canton R, Gniadkowski M et al (2007) CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother 59(2):165–174
Rossolini GM, D'Andrea MM, Mugnaioli C (2008) The spread of CTX-M-type extended-spectrum beta-lactamases. Clin Microbiol Infect 14 [Suppl 1]:33–41
Rodríguez-Baño J, Navarro MD, Romero L, Muniain MA, de Cueto M, Rios MJ, Hernandez JR, Pascual A (2006) Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis 43(11):1407–1414
Melzer M, Petersen I (2007) Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli. J Infect 55(3):254–259
Metan G, Zarakolu P, Cakir B, Hascelik G, Uzun O (2005) Clinical outcomes and therapeutic options of bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Int J Antimicrob Agents 26(3):254–257
Tumbarello M, Sanguinetti M, Montuori E et al (2007) Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother 51(6):1987–1994
Galas M, Decousser JW, Breton N, Godard T, Allouch PY, Pina P (2008) Nationwide study of the prevalence, characteristics, and molecular epidemiology of extended-spectrum-beta-lactamase-producing Enterobacteriaceae in France. Antimicrob Agents Chemother 52(2):786–789
Pallecchi L, Bartoloni A, Fiorelli C et al (2007) Rapid dissemination and diversity of CTX-M extended-spectrum beta-lactamase genes in commensal Escherichia coli isolates from healthy children from low-resource settings in Latin America. Antimicrob Agents Chemother 51(8):2720–2725
Ho PL, Poon WW, Loke SL et al (2007) Community emergence of CTX-M type extended-spectrum beta-lactamases among urinary Escherichia coli from women. J Antimicrob Chemother 60(1):140–144
Du B, Long Y, Liu H et al (2002) Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome. Intensive Care Med 28(12):1718–1723
Kang CI, Cheong HS, Chung DR et al (2008) Clinical features and outcome of community-onset bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Eur J Clin Microbiol Infect Dis 27(1):85–88
Jarlier V, Nicolas MH, Fournier G, Philippon A (1988) Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis 10(4):867–878
Drieux L, Brossier F, Sougakoff W, Jarlier V (2008) Phenotypic detection of extended-spectrum beta-lactamase production in Enterobacteriaceae: review and bench guide. Clin Microbiol Infect 14 [Suppl 1]:90–103
Friedman ND, Kaye KS, Stout JE et al (2002) Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137(10):791–797
Tenover FC, Arbeit RD, Goering RV et al (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33(9):2233–2239
Clermont O, Bonacorsi S, Bingen E (2000) Rapid and simple determination of the Escherichia coli phylogenetic group. Appl Environ Microbiol 66(10):4555–4558
Brasme L, Nordmann P, Fidel F et al (2007) Incidence of class A extended-spectrum beta-lactamases in Champagne-Ardenne (France): a 1 year prospective study. J Antimicrob Chemother 60(5):956–964
Lavigne JP, Marchandin H, Delmas J et al (2007) CTX-M beta-lactamase-producing Escherichia coli in French hospitals: prevalence, molecular epidemiology, and risk factors. J Clin Microbiol 45(2):620–626
Poirel L, Gniadkowski M, Nordmann P (2002) Biochemical analysis of the ceftazidime-hydrolysing extended-spectrum beta-lactamase CTX-M-15 and of its structurally related beta-lactamase CTX-M-3. J Antimicrob Chemother 50(6):1031–1034
Boyd DA, Tyler S, Christianson S et al (2004) Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum beta-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrob Agents Chemother 48(10):3758–3764
Machado E, Coque TM, Canton R, Baquero F, Sousa JC, Peixe L (2006) Dissemination in Portugal of CTX-M-15-, OXA-1-, and TEM-1-producing Enterobacteriaceae strains containing the aac(6′)-Ib-cr gene, which encodes an aminoglycoside- and fluoroquinolone-modifying enzyme. Antimicrob Agents Chemother 50(9):3220–3221
Lavollay M, Mamlouk K, Frank T et al (2006) Clonal dissemination of a CTX-M-15 beta-lactamase-producing Escherichia coli strain in the Paris area, Tunis, and Bangui. Antimicrob Agents Chemother 50(7):2433–2438
Eckert C, Gautier V, Arlet G (2006) DNA sequence analysis of the genetic environment of various blaCTX-M genes. J Antimicrob Chemother 57(1):14–23
Leflon-Guibout V, Jurand C, Bonacorsi S et al (2004) 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 48(10):3736–3742
Karim A, Poirel L, Nagarajan S, Nordmann P (2001) Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett 201(2):237–241
Lavigne JP, Marchandin H, Delmas J et al (2006) qnrA in CTX-M-producing Escherichia coli isolates from France. Antimicrob Agents Chemother 50(12):4224–4228
Cambau E, Lascols C, Sougakoff W et al (2006) Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002–2005. Clin Microbiol Infect 12(10):1013–1020
Poirel L, Leviandier C, Nordmann P (2006) Prevalence and genetic analysis of plasmid-mediated quinolone resistance determinants QnrA and QnrS in Enterobacteriaceae isolates from a French university hospital. Antimicrob Agents Chemother 50(12):3992–3997
Jiang Y, Zhou Z, Qian Y et al (2008) Plasmid-mediated quinolone resistance determinants qnr and aac(6′)-ib-cr in extended-spectrum {beta}-lactamase-producing Escherichia coli and Klebsiella pneumoniae in China. J Antimicrob Chemother 61(5):1003–1006
Iabadene H, Messai Y, Ammari H et al (2008) Dissemination of ESBL and Qnr determinants in Enterobacter cloacae in Algeria. J Antimicrob Chemother 62(1):133–136
Rodríguez-Baño J, Navarro MD, Romero L et al (2008) Risk-factors for emerging bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Clin Microbiol Infect 14(2):180–183
Kang CI, Kim SH, Park WB et al (2004) Bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy. Antimicrob Agents Chemother 48(12):4574–4581
Kim YK, Pai H, Lee HJ et al (2002) Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother 46(5):1481–1491
Herzer PJ, Inouye S, Inouye M, Whittam TS (1990) Phylogenetic distribution of branched RNA-linked multicopy single-stranded DNA among natural isolates of Escherichia coli. J Bacteriol 172(11):6175–6181
Boyd EF, Hartl DL (1998) Chromosomal regions specific to pathogenic isolates of Escherichia coli have a phylogenetically clustered distribution. J Bacteriol 180(5):1159–1165
Mamlouk K, Boutiba-Ben Boubaker I, Gautier V et al (2006) Emergence and outbreaks of CTX-M beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae strains in a Tunisian hospital. J Clin Microbiol 44(11):4049–4056
Kassis-Chikhani N, Vimont S, Asselat K et al (2004) CTX-M beta-lactamase-producing Escherichia coli in long-term care facilities, France. Emerg Infect Dis 10(9):1697–1698
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Drieux, L., Brossier, F., Duquesnoy, O. et al. Increase in hospital-acquired bloodstream infections caused by extended spectrum β-lactamase-producing Escherichia coli in a large French teaching hospital. Eur J Clin Microbiol Infect Dis 28, 491–498 (2009). https://doi.org/10.1007/s10096-008-0656-6
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DOI: https://doi.org/10.1007/s10096-008-0656-6