Outbreak of vancomycin‐resistant <i>Enterococcus faecium</i> in a haematology unit: risk factor assessment and successful control of the epidemic

Timmers, G.J.; Zwet, W.C. van der; Simoons-Smit, Ina M.; Meester, H. H. M.; Vandenbroucke-Grauls, Christina M. J. E.; Huijgens, Peter C.

doi:10.1046/j.0007-1048.2002.03339.x

Cited by 60 publications

(45 citation statements)

References 31 publications

(47 reference statements)

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“…Sixty-three isolates of E. faecium (32 ciprofloxacin resistant and 31 ciprofloxacin susceptible) were collected from 10 different countries from nosocomial epidemics (n ϭ 13; United Kingdom, n ϭ 1; The Netherlands, n ϭ 5; United States, n ϭ 7), clinical infections (n ϭ 27; Austria, n ϭ 2; Germany, n ϭ 4; Spain, n ϭ 3; France, n ϭ 2; United Kingdom, n ϭ 2; Israel, n ϭ 1; Italy, n ϭ 3; The Netherlands, n ϭ 6; Portugal, n ϭ 3; United States, n ϭ 7) (e.g., from blood, urine, or wounds), surveillance for colonization among hospitalized patients and in the community (France, n ϭ 3; The Netherlands, n ϭ 8) (all fecal samples), and animals (The Netherlands, n ϭ 12) (2,4,10,24,32,54,65). Strains were considered epidemic as defined before (65).…”

Section: Methodsmentioning

confidence: 99%

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

et al. 2006

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To substantiate a common genetic background of ciprofloxacin-resistant Enterococcus faecium, 32 ciprofloxacin-resistant (Cip r ) and 31 ciprofloxacin-susceptible (Cip s ) isolates from outbreaks, clinical infections, surveillances, and animals from 10 different countries were genotyped by multilocus sequence typing. Additionally, susceptibilities to ampicillin and vancomycin and the presence of esp were determined and the quinolone resistance-determining regions of parC, gyrA, parB, and gyrE were sequenced. High-level Cip r (MIC > 64 g/ml) due to point mutations in the quinolone resistance-determining region was unique to a distinct hospital-adapted genetic complex in E. faecium, previously designated CC17. Low-level Cip r (MIC ‫؍‬ 4 g/ml) in non-CC17 strains is not attributable to point mutations in any subunit of the topoisomerase genes, and the mechanism of resistance remains unclear. Acquisition of mutations in parC and gyrA, leading to high-level Cip r , is, in addition to ampicillin resistance and the presence of a putative pathogenicity island, another cumulative step in hospital adaptation of CC17.Over the last two decades, enterococci have become increasingly important as nosocomial pathogens (3). These organisms are intrinsically resistant to a large number of antimicrobials and have the ability to easily acquire new resistance traits (40, 50). The emergence of nosocomial infections caused by ampicillin-, high-level aminoglycoside-, and glycopeptide-resistant Enterococcus faecium has caused clinical concern due to intraand interhospital spread and limited therapeutic options (40, 50). Glycopeptide-resistant enterococci (vancomycin-resistant enterococci [VRE]) are nowadays endemic to the United States, with ϳ30% of enterococcal infections caused by VRE (38, 43); in Europe, the epidemiology of VRE is now changing from a near absence of VRE in hospital-acquired infections at the turn of the century to a situation in which nosocomial epidemics and infections are increasingly reported (3, 13, 17). We recently described a hospital-adapted genetic subtype of E. faecium associated with epidemics and clinical infections, which has spread globally (20,32,62,65). This subpopulation belongs to a distinct genetic lineage labeled clonal complex 17 (CC17) (62) and is associated with the presence of the variant esp gene as part of a pathogenicity island (31) and resistance to ampicillin. Recently, resistance to ciprofloxacin appeared to be associated with ampicillin resistance in genotypically related E. faecium isolates from Norway (25,55,56) and Spain (7).To substantiate a common genetic background of quinoloneresistant E. faecium and association with the hospital-adapted CC17, we studied the genetic relatedness of 32 ciprofloxacinresistant and 31 ciprofloxacin-susceptible E. faecium isolates from various human and animal origins by multilocus sequence typing (MLST) and determined susceptibility to vancomycin and ampicillin and the presence of esp. Finally, we sequenced the quinolone resistance-determining regions (...

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Section: Methodsmentioning

confidence: 99%

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

et al. 2006

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“…E. faecium isolate E300 from hospital outbreak US-1 (11,65) was used to clone and sequence the esp gene and the DNA region encompassing the putative PAI. E. faecium isolate E734 from hospital outbreak NL-1-1 (64,65) and strain E470 from hospital outbreak NL-3-1 (58,65) were used to determine sequence heterogeneity in the N-and C-terminal domains of the esp gene. Sequencing of the frameshift mutation at positions 12830 to 12832 and the stop codon at position 13719, originally found in strain E300, was performed for isolates E155 from outbreak US-2-6 (5, 65) and E734 from outbreak NL-1-1 (64,65).…”

Section: Methodsmentioning

confidence: 99%

A Novel Putative Enterococcal Pathogenicity Island Linked to theespVirulence Gene ofEnterococcus faeciumand Associated with Epidemicity

Leavis¹,

Top²,

et al. 2004

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Enterococcus faecalis harbors a virulence-associated surface protein encoded by the esp gene. This gene has been shown to be part of a 150-kb putative pathogenicity island. A gene similar to esp has recently been found in Enterococcus faecium isolates recovered from hospitalized patients. In the present study we analyzed the polymorphism in the esp gene of E. faecium, and we investigated the association of esp with neighboring chromosomal genes. The esp gene showed considerable sequence heterogeneity in the regions encoding the nonrepeat N-and C-terminal domains of the Esp protein as well as differences in the number of repeats. DNA sequencing of chromosomal regions flanking the esp gene of E. faecium revealed seven open reading frames, representing putative genes implicated in virulence, regulation of transcription, and antibiotic resistance. These flanking regions were invariably associated with the presence or absence of the esp gene in E. faecium, indicating that esp in E. faecium is part of a distinct genetic element. Because of the presence of virulence genes in this gene cluster, the lower G؉C content relative to that of the genome, and the presence of esp in E. faecium isolates associated with nosocomial outbreaks and clinically documented infections, we conclude that this genetic element constitutes a putative pathogenicity island, the first one described in E. faecium. Except for the presence of esp and araC, this pathogenicity island is completely different from the esp-containing pathogenicity island previously disclosed in E. faecalis.Enterococci are common inhabitants of the gastrointestinal tracts of humans and animals, and although they have been recognized as pathogens able to cause endocarditis, they were generally considered second-rate pathogens. Recent estimates, however, indicate that enterococci are now among the leading causes of nosocomial infections (57). Of all enterococcal species, Enterococcus faecalis accounted for the most infections in humans (26). However, during the past decade, the incidence of bloodstream infections caused by Enterococcus faecium increased, an increase which has been linked to the emergence of antibiotic resistance in this species (26,40).Little is known about virulence determinants in E. faecium (20). Recently, however, three potential virulence genes, esp, hyl, and acm, have been described for E. faecium. They were all found more frequently in clinical isolates than in fecal isolates or nonhuman isolates (13,41,44,65).Of these three putative virulence genes, only the esp gene is also found in E. faecalis (51). The Esp protein in E. faecalis is expressed as a large surface-exposed protein with a molecular mass of approximately 202 kDa. In E. faecalis, Esp is thought to be an adhesin contributing to colonization of urinary tract epithelial cells and biofilm formation (50, 59). Although detailed experimental evidence is not yet available, the higher prevalence of the E. faecium esp gene in clinical isolates suggests a role of Esp in the pathogenesis of E. faeci...

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“…10,11 Maintenance of lowlevel endemicity after a large outbreak has been achieved 12,13 as has eradication following a small outbreak 14 and in specific units. [15][16][17] Successful control has also been reported in a healthcare region that included long-term-care facilities. 18 In that report, however, only 38 patients were found to be colonized during a 2-year period.…”

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confidence: 99%

Eradication of a Large Outbreak of a Single Strain of vanB Vancomycin-Resistant Enterococcus faecium at a Major Australian Teaching Hospital

Christiansen

Tibbett

Beresford

et al. 2004

Infect. Control Hosp. Epidemiol.

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Objective:To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital.Interventions:Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistantEnterococcus faeciumdespite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection ofvanA andvanBresistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin).Results:A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistantE. faecium.Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars).Conclusion:Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.

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Outbreak of vancomycin‐resistant Enterococcus faecium in a haematology unit: risk factor assessment and successful control of the epidemic

Cited by 60 publications

References 31 publications

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium

A Novel Putative Enterococcal Pathogenicity Island Linked to theespVirulence Gene ofEnterococcus faeciumand Associated with Epidemicity

Eradication of a Large Outbreak of a Single Strain of vanB Vancomycin-Resistant Enterococcus faecium at a Major Australian Teaching Hospital

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