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Coagulase-negative staphylococci in hematological malignancy
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.

In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:

In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.

In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.

In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.

Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.

In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2013. , p. 56
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 95
Keyword [en]
coagulase-negative staphylococci, hematological malignancy, Staphylococcus epidermidis, healthcare-associated infection, antibiotic susceptibility, molecular epidemiology, bloddstream infection, bacteremia
National Category
Hematology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-30750ISBN: 978-91-7668-970-7 (print)OAI: oai:DiVA.org:oru-30750DiVA, id: diva2:646457
Public defence
2013-10-15, Wilandersalen, Universitetssjukhuset i Örebro, S. Grev Roseng. 18, 703 62 ÖREBRO, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-09-09 Created: 2013-09-09 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
Open this publication in new window or tab >>Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
Show others...
2011 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 11, p. 1349-1354Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to determine if there was a long-term increase in glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated from patients with hematological malignancies. We conducted a retrospective single-center study where all positive blood cultures of S. epidermidis (n = 387) and S. haemolyticus (n = 19) isolated from patients with hematological malignancies during three decades, 1980 to 2009, were re-evaluated for the presence of reduced susceptibility to vancomycin and teicoplanin. Three different methods for the detection of reduced susceptibility to glycopeptides were used; standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD) Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin and teicoplanin did not show any statistically significant increase during the study period. The presence of heterogeneously glycopeptide-intermediate staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci (CoNS) isolates. hGIS were found in 31-45% of the CoNS isolates by the macromethod Etest and in 53-67% by the GRD Etest during the three decades. In conclusion, we did not observe any long-term glycopeptide MIC creep determined by the standard Etest, although a high and increasing proportion of heterogeneous vancomycin resistance was observed.

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-20840 (URN)10.1007/s10096-011-1228-8 (DOI)000295864800006 ()
Available from: 2012-01-11 Created: 2012-01-11 Last updated: 2017-12-08Bibliographically approved
2. Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
Open this publication in new window or tab >>Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
2012 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, p. 1679-1687Article in journal (Refereed) Published
Abstract [en]

The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.

Place, publisher, year, edition, pages
New York, USA: Springer, 2012
National Category
Clinical Medicine Infectious Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22579 (URN)10.1007/s10096-011-1493-6 (DOI)000304652800051 ()22124538 (PubMedID)2-s2.0-84865591558 (Scopus ID)
Note

Funding Agency:

research committee of Örebro County Council, Sweden

Available from: 2012-04-18 Created: 2012-04-18 Last updated: 2018-04-16Bibliographically approved
3. Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
Open this publication in new window or tab >>Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
Show others...
2014 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed) Published
Abstract [en]

The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keyword
coagulase-negative staphylococci; Staphylococcus epidermidis; hematological malignancy; blood culture contamination
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-32422 (URN)10.1111/apm.12182 (DOI)000336447200011 ()24106819 (PubMedID)2-s2.0-84901231876 (Scopus ID)
Note

Funding Agency:

Örebro County Council Research committee 

Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2018-04-05Bibliographically approved
4. Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with haematological malignancies
Open this publication in new window or tab >>Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with haematological malignancies
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Staphylococcus epidermidis is an important cause of bloodstream infections in patients with haematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for haematological malignancies at the University Hospital of Örebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson’s Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). These two STs were isolated during the entire study period, and together caused temporal peaks in the incidence of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, the proportion of methicillin resistance was 257/271 (95%); 234/271 (86%) displayed a multidrug-resistant phenotype. In conclusion, in this long-term study of patients with haematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

Keyword
Staphylococcus epidermidis, Bloodstream infection, Haematological malignancy, Multilocus sequence typing, Coagulase-negative staphylococci, Molecular epidemiology, Healthcare-associated infection
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-32423 (URN)
Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2017-10-17Bibliographically approved

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