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Clonality among ampicillin-resistant Enterococcus faecium in Sweden and relation to ciprofloxacin resistance
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2003 (English)In: Clinical Microbiology and Infection, ISSN 1198-743X, Vol. 9, no 10, 1011-1019 p.Article in journal (Refereed) Published
Abstract [en]

Objective To investigate clonal relationships in a nationwide sample of human Enterococcus faecium isolates. Methods Biochemical fingerprinting (PhP (PhenePlate) typing) was used to compare 180 fecal ampicillin-resistant E. faecium (ARE) isolates with 169 matched fecal ampicillin-susceptible E. faecium (ASE) isolates from patients in 23 hospitals, collected in 1998, and to study 39 fecal ARE isolates from non-hospitalized individuals collected in 1998, and five ARE and 29 ASE isolates from the early 1990s. Representative ARE and ASE isolates were subjected to pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA and sequencing of the regions encoding the fluoroquinolone targets of the enzymes GyrA and ParC. Results Both PhP and PFGE results showed a higher homogeneity among ARE than among ASE isolates (P < 0.001). One PhP type (FMSE1) comprised 73% of the hospital ARE isolates (53% of ARE isolates from non-hospitalized individuals, and four of five ARE isolates from the early 1990s), but only 1% of the ASE isolates. PFGE of the hospital E. faecium isolates revealed that 23 of the 25 ARE isolates and one of the 22 ASE isolates were of one dominating type. High-level resistance to ciprofloxacin (MIC > 16 mg/L) was present in 91% of ARE isolates, whereas only low-level resistance (MIC 4–16 mg/L; 35% of isolates) was found among ASE isolates. One mutation in parC (codon 80) and one of two mutations in gyrA (codons 83 or 87) were detected in all ARE isolates tested with high-level ciprofloxacin resistance, but were lacking in ARE and ASE isolates with low-level ciprofloxacin resistance. Conclusion Most ARE isolates in Sweden were clonally related. High-level ciprofloxacin resistance was found in ARE isolates of PhP type FMSE1 as well as in other PhP types, but never in ASE isolates.

Place, publisher, year, edition, pages
2003. Vol. 9, no 10, 1011-1019 p.
Keyword [en]
ARE clonality, ciprofloxacin resistance, PhP, gyrA, parC, PFGE
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-90182DOI: 10.1046/j.1469-0691.2003.00701.xOAI: oai:DiVA.org:uu-90182DiVA: diva2:162446
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2009-09-25Bibliographically approved
In thesis
1. Epidemiology of Enterococci with Acquired Resistance to Antibiotics in Sweden: Special emphasis on Ampicillin and Vancomycin
Open this publication in new window or tab >>Epidemiology of Enterococci with Acquired Resistance to Antibiotics in Sweden: Special emphasis on Ampicillin and Vancomycin
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Enterokocker med förvärvad resistens mot ampicillin och vancomycin i Sverige
Abstract [en]

The first hospital outbreak of vancomycin-resistant enterococci (VRE) and carriage rates of VRE and ampicillin-resistant enterococci (ARE) in Sweden were investigated. Clonal relationships and mutations in fluoroquinolone resistance determining regions among ARE collected nation-wide were studied. Risk factors for ARE infection, shedding of ARE and the presence of the virulence gene esp in ARE isolates and patients on a hematology unit and other units at Uppsala University Hospital were further investigated.

The first Swedish hospital VRE outbreak was due to clonal spread of E. faecium, vanA. The nation wide carriage rates of ARE and VRE were 21.5% / 1% and 6% / 0%, among hospitalized patients and non-hospitalized individuals respectively. All ARE and VRE were E. faecium and >90% resistant to ciprofloxacin. All VRE carried vanB. Carriage of ARE was independently associated with >5 days of antibiotic treatment. Phenotypic and genetic typing showed a significantly higher homogeneity among ARE compared to matched ASE E. faecium isolates. Mutations conferring high-level ciprofloxacin resistance were found only in ARE. Risk factors for ARE infection included long duration of hospital stay and exposure to antibiotics. Skin carriage was associated with ARE shedding. ARE bacteremia was independently associated with prior ARE colonization and hematopoietic stem cell transplantation. Death was more common in ARE septicemia cases compared to controls. Esp was significantly more common in ARE surveillance compared to ARE blood isolates from patients on the hematology ward.

In conclusion, VRE were rare but clonally related multi-resistant ARE E. faecium were highly prevalent in Swedish hospitals. Spread of ARE in hospitals during the 1990s is suggested to be the main explanation for the emergence of ARE in Sweden. Spread was facilitated by use of antibiotics and probably by the presence of virulence genes in E. faecium isolates.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 80 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1237
Communicable diseases, Antimicrobial resistance, enterococci, epidemiology in Sweden, intra-hospital spread, shedding, risk-factors, infection, colonization, virulence factors, ARE, VRE, Php, PFGE, esp, gyrA, parC, Infektionssjukdomar
National Category
Infectious Medicine
Research subject
Infectious Diseases
urn:nbn:se:uu:diva-3344 (URN)91-554-5574-3 (ISBN)
Public defence
2003-04-24, Avdelningen för Klinisk Mikrobiologi, Hörsalen, Dag hammarskölds väg 17, Uppsala, 09:15
Available from: 2003-03-28 Created: 2003-03-28Bibliographically approved

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