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Epidemiological and molecular biological studies of multi-resistant methicillin-susceptible Staphylococcus aureus
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotic resistance is increasingly recognised as a major problem and threat. During the last decades Gram-positive bacteria in general, and methicillin-resistant Staphylococcus aureus (MRSA) in particular, have been in focus both concerning matters of antibiotic resistance and as pathogens causing health care-associated (nosocomial) infections. In contrast to MRSA, studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. However, interest in MSSA has increased since it was shown that MRSA emerges from susceptible backgrounds by acquisition of a staphylococcal cassette chromosome element, carrying the mecA gene encoding methicillin-resistance (SCCmec).

In an outbreak investigation of MRSA in Östergötland County, Sweden, in 2005, a high incidence of MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin (ECT-R) was detected. Analysis showed that 91 % of the investigated isolates were genetically related (clonal). The ECT-R clone was divided into four different but closely related patterns with pulsed-field gel electrophoresis (PFGE), and was designated spa type t002. Whole genome sequencing revealed that the ECT-R clone carried a pseudo-SCC element estimated to be 12 kb in size, showing a resemblance of more than 99 % with the SCCmec type II element of MRSA strain N315 (New York/Japan clone). This suggested a probable derivation from a highly successful MRSA strain, which had partially excised its SCCmec. The clonal outbreak was concentrated in eight hospital departments and two primary care centres, all located in the city of Linköping. Despite a high exchange of patients with the hospitals in the neighbouring counties in southeast Sweden (Jönköping- and Kalmar County), the ECT-R clone seemed to be limited to Östergötland County. However, a tobramycin-resistant clone predominated by isolates of spa type t084 was found in all three counties in southeast Sweden, and in particular among newborns, suggesting inter-hospital transmission.

The ECT-R clone has survived as an abundant MSSA clone for a decade in Östergötland County, which indicates an insufficiency in the maintenance of basic hygiene guidelines, and that the clone probably possesses mechanisms of virulence and transmission that are yet to be discovered.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. , 63 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1386
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-103679DOI: 10.3384/diss.diva-103679ISBN: 978-91-7519-444-8 (print)OAI: oai:DiVA.org:liu-103679DiVA: diva2:690110
Public defence
2014-02-28, Eken, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2014-01-22 Created: 2014-01-22 Last updated: 2014-01-27Bibliographically approved
List of papers
1. A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county
Open this publication in new window or tab >>A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county
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2009 (English)In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 41, no 5, 324-333 p.Article in journal (Refereed) Published
Abstract [en]

In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18138 (URN)10.1080/00365540902801202 (DOI)
Available from: 2009-05-09 Created: 2009-05-08 Last updated: 2014-01-22
2. Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county
Open this publication in new window or tab >>Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county
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2012 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 2, 141-147 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in A-stergotland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type I (TM) I (TM) element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74635 (URN)10.1007/s10096-011-1286-y (DOI)000298855900006 ()
Note

Funding Agencies|Ostergotland County Council||Scandinavian Society for Antimicrobial Chemotherapy (SSAC)|2009-22495|

Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08
3. Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
Open this publication in new window or tab >>Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.

Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.

Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.

Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.

Keyword
MSSA, multi-resistance, genetic relatedness, t002, t084
National Category
Clinical Medicine Medical Genetics
Identifiers
urn:nbn:se:liu:diva-103678 (URN)
Available from: 2014-01-22 Created: 2014-01-22 Last updated: 2015-04-01Bibliographically approved

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