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Tilevik, Diana
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Publications (10 of 22) Show all publications
Enroth, H., Retz, K., Andersson, S., Andersson, C., Svensson, K., Ljungström, L., . . . Pernestig, A.-K. (2019). Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection. Infectious Diseases, 51(4), 249-258
Open this publication in new window or tab >>Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection
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2019 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 4, p. 249-258Article in journal (Refereed) Published
Abstract [en]

Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.

Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.

Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.

Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
MALDI-TOF MS analysis, QuickFISH®, sepsis diagnostics, blood culture, Maldi Sepsityper™
National Category
Other Medical Engineering Microbiology in the medical area Infectious Medicine Biomedical Laboratory Science/Technology
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-16603 (URN)10.1080/23744235.2018.1554258 (DOI)000465440800002 ()30729840 (PubMedID)2-s2.0-85061188564 (Scopus ID)
Funder
Knowledge Foundation
Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-09-03Bibliographically approved
Dave, V. P., Ngo, T. A., Pernestig, A.-K., Tilevik, D., Kanit, K., Nguyen, T., . . . Bang, D. D. (2018). MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics. Laboratory Investigation, 99(4), 452-469
Open this publication in new window or tab >>MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics
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2018 (English)In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 99, no 4, p. 452-469Article, review/survey (Refereed) Published
Abstract [en]

The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling-based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
Keywords
IN-SITU HYBRIDIZATION, ELECTROCHEMICAL BIOSENSORS, CIRCULATING MICRORNAS, MICROFLUIDIC PLATFORM, CANCER DIAGNOSTICS, EXPRESSION, BIOMARKERS, ACID, PROBES, RNA
National Category
Biochemistry and Molecular Biology Medical Biotechnology
Research subject
Infection Biology; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-16509 (URN)10.1038/s41374-018-0143-3 (DOI)000462161500002 ()30542067 (PubMedID)2-s2.0-85058447908 (Scopus ID)
Projects
SMARTDIAGNOS
Funder
EU, Horizon 2020, 68797
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2019-04-04Bibliographically approved
Ljungström, L., Pernestig, A.-K., Jacobsson, G., Andersson, R., Usener, B. & Tilevik, D. (2017). Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS ONE, 12(7), Article ID e018704.
Open this publication in new window or tab >>Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e018704Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.

METHODS:

Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).

RESULTS:

For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).

CONCLUSIONS:

Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

National Category
Clinical Medicine
Research subject
Infection Biology; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-14004 (URN)10.1371/journal.pone.0181704 (DOI)000406634500106 ()28727802 (PubMedID)2-s2.0-85024853446 (Scopus ID)
Available from: 2017-08-18 Created: 2017-08-18 Last updated: 2018-06-01Bibliographically approved
Retz, K., Andersson, S., Andersson, C., Svensson, K., Ljungström, L., Enroth, H., . . . Pernestig, A.-K. (2017). Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting. In: : . Paper presented at 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna, Austria, 22 – 25 April 2017.
Open this publication in new window or tab >>Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting
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2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Clinical Medicine Microbiology in the medical area
Research subject
Infection Biology; INF000
Identifiers
urn:nbn:se:his:diva-13599 (URN)
Conference
27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna, Austria, 22 – 25 April 2017
Projects
Future sepsis diagnostics
Funder
Knowledge Foundation
Available from: 2017-06-02 Created: 2017-06-02 Last updated: 2018-11-16Bibliographically approved
Wallenhammar, A.-C., Algerin, M. & Tilevik, D. (2017). Ny metod bedömer risk för bomullsmögel. Arvensis (3)
Open this publication in new window or tab >>Ny metod bedömer risk för bomullsmögel
2017 (Swedish)In: Arvensis, ISSN 2000-0871, no 3Article in journal (Other academic) Published
National Category
Agricultural Science Biochemistry and Molecular Biology
Research subject
Biotechnology; Infection Biology; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-14549 (URN)
Funder
Knowledge Foundation
Available from: 2017-12-05 Created: 2017-12-05 Last updated: 2018-12-27Bibliographically approved
Ljungström, L., Jacobsson, G., Pernestig, A.-K. & Tilevik, D. (2017). The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis. In: : . Paper presented at European Congress of Clinical Microbiology and Infectious Diseases. ECCMID
Open this publication in new window or tab >>The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis
2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
ECCMID, 2017
Keywords
severe sepsis, sepsis definition, biomarkers, bacteraemia
National Category
Medical Biotechnology Clinical Laboratory Medicine Infectious Medicine
Research subject
Infection Biology; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-13550 (URN)
Conference
European Congress of Clinical Microbiology and Infectious Diseases
Funder
Knowledge Foundation
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2018-11-16Bibliographically approved
Helldin, T., Pernestig, A.-K. & Tilevik, D. (2017). Towards a Clinical Support System for the Early Diagnosis of Sepsis. In: Vincent G. Duffy (Ed.), Digital Human Modeling - Applications in Health, Safety, Ergonomics, and Risk Management: Health and Safety: 8th International Conference, DHM 2017 Held as Part of HCI International 2017 Vancouver, BC, Canada, July 9–14, 2017, Proceedings, Part II. Paper presented at 8th International Conference on Digital Human Modeling and Applications in Health, Safety, Ergonomics, and Risk Management, DHM 2017, held as part of 19th International Conference on Human-Computer Interaction, HCI 2017, Vancouver, Canada, July 9–14, 2017 (pp. 23-35). Springer
Open this publication in new window or tab >>Towards a Clinical Support System for the Early Diagnosis of Sepsis
2017 (English)In: Digital Human Modeling - Applications in Health, Safety, Ergonomics, and Risk Management: Health and Safety: 8th International Conference, DHM 2017 Held as Part of HCI International 2017 Vancouver, BC, Canada, July 9–14, 2017, Proceedings, Part II / [ed] Vincent G. Duffy, Springer, 2017, p. 23-35Conference paper, Published paper (Refereed)
Abstract [en]

Early and accurate diagnosis of sepsis is critical for patientsafety. However, this is a challenging task due to the very general symptomsassociated with sepsis, the immaturity of the tools used by theclinicians as well as the time-delays associated with the diagnostic methodsused today. This paper explores current literature regarding guidelinesfor clinical decision support, and support for sepsis diagnosis inparticular, together with guidelines extracted from interviews with fourclinicians and one biomedical analyst working at a hospital and clinicallaboratory in Sweden. The results indicate the need for the developmentof visual and interactive aids for enabling early and accurate diagnosisof sepsis.

Place, publisher, year, edition, pages
Springer, 2017
Series
Lecture Notes in Computer Science, ISSN 0302-9743, E-ISSN 1611-3349 ; 10287
Keywords
Clinical decision support, sepsis, guidelines, system transparency, electronic health record
National Category
Computer Sciences
Research subject
Skövde Artificial Intelligence Lab (SAIL); Infection Biology; INF301 Data Science; INF502 Biomarkers
Identifiers
urn:nbn:se:his:diva-13975 (URN)10.1007/978-3-319-58466-9_3 (DOI)2-s2.0-85025140829 (Scopus ID)978-3-319-58466-9 (ISBN)978-3-319-58465-2 (ISBN)
Conference
8th International Conference on Digital Human Modeling and Applications in Health, Safety, Ergonomics, and Risk Management, DHM 2017, held as part of 19th International Conference on Human-Computer Interaction, HCI 2017, Vancouver, Canada, July 9–14, 2017
Projects
SepsIT
Available from: 2017-08-11 Created: 2017-08-11 Last updated: 2018-11-16Bibliographically approved
Tilevik, D. (2016). Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting. Infection Ecology & Epidemiology, 6, Article ID 31234.
Open this publication in new window or tab >>Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting
2016 (English)In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, article id 31234Article in journal (Refereed) Published
Abstract [en]

Background: The increasing prevalence of penicillin non-susceptible pneumococci (PNSP) throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting.

Methods: An individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden). A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed.

Results: Model simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year), the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community.

Conclusion: The frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

Place, publisher, year, edition, pages
CoAction Publishing, 2016
Keywords
pneumococci, network model, infectious disease epidemiology, penicillin non-susceptible pneumococci, individual-based, Streptococcus pneumoniae, antibiotic resistance
National Category
Infectious Medicine
Research subject
Natural sciences; Infection Biology
Identifiers
urn:nbn:se:his:diva-12299 (URN)10.3402/iee.v6.31234 (DOI)27206408 (PubMedID)
Available from: 2016-05-25 Created: 2016-05-25 Last updated: 2018-11-15Bibliographically approved
Ljungström, L., Enroth, H., Claesson, B. E. B., Ovemyr, I., Karlsson, J., Fröberg, B., . . . Karlsson, D. (2015). Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis. BMC Infectious Diseases, 15(1), Article ID 199.
Open this publication in new window or tab >>Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis
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2015 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, no 1, article id 199Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis.

METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity.

RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results.

CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keywords
Blood culture, Magicplex (TM), Prove-it (TM), sepsis diagnostic, multiplex PCR, microarray
National Category
Clinical Medicine
Research subject
Medical sciences; Infection Biology
Identifiers
urn:nbn:se:his:diva-10970 (URN)10.1186/s12879-015-0938-4 (DOI)000353758100001 ()25928122 (PubMedID)2-s2.0-84928688856 (Scopus ID)
Projects
The Skaraborg sepsis study, Skövde, Sweden
Funder
Knowledge Foundation
Available from: 2015-05-28 Created: 2015-05-28 Last updated: 2018-11-15Bibliographically approved
Karlsson, D., Pernestig, A.-K. & Ljungström, L. (2015). Multimarker approach for sepsis diagnostics. In: 25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015: . Paper presented at 25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015. European Society of ClinicalMicrobiology and Infectious Diseases (ESCMID)
Open this publication in new window or tab >>Multimarker approach for sepsis diagnostics
2015 (English)In: 25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015, European Society of ClinicalMicrobiology and Infectious Diseases (ESCMID) , 2015Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

OBJECTIVES

The aim of this study was to assess the performance of a multimarker model in distinguishing patients with sepsis from those with non-infective systemic inflammatory response.

METHODS

This study is part of a prospective study of community-onset severe sepsis and septic shock in adults conducted from September 2011 to June 2012 at Skaraborg Hospital, in the western region of Sweden. The levels of 92 inflammation-related human protein biomarkers were measured simultaneously using Proseek® Multiplex Inflammation I96x96 (Olink Bioscience, Sweden) in 122 plasma samples collected from patients suspected with sepsis. After pre-processing normalization procedure, measurements of the markers were obtained as Normalized Protein eXpression (NPX) units on a log2 scale (GenEx, MultiD Analyses AB, Sweden). The study was approved by the Regional Ethical Review Board of Gothenburg (376-11). All patients enrolled provided written informed consent.

To reduce the number of markers, factor analysis was performed. Thereafter, a multimarker model for classification was derived using discriminant analysis. The multimarker model consisted of a linear function of the selected markers. Cross-validation was performed by classifying each sample by the discriminant function derived from all samples other than that specific sample. The performance was assessed as area under receiving operating characteristic (ROC) curve. The cut-off for sensitivity and specificity was derived from the cut score of the discriminant function. Statistical analyses were performed in SPSS 22.0 (IBM Corporation Somers, NY USA).

RESULTS

Of the 122 samples, 80 (66%) were from patients diagnosed with sepsis and 42 from patients with non-infective systemic inflammatory response syndrome (SIRS). The five markers selected for the multimarker model were interleukin-6 (IL-6), cystatin D (CST5), delta and notch-like epidermal growth factor-related receptor (DNER), STAM-binding protein (STAMPB), macrophage colony-stimulating factor 1 (CSF 1). Every single marker was statistically different between the groups (p value < 0.001), except for DNER (p value 0.064) and STAMPB (p value 0.060). The area under ROC was higher for the multimarker model (81%) than for each biomarker separately (Figure 1). The accuracy for the multimarker model was 72% [64-80, 95% CI]; sensitivity 84% [77-91, 95% CI]; specificity 60% [51-69, 95% CI]; positive predictive value 79% [72-86, 95% CI]; and negative predictive value 66% [58-74, 95% CI].

CONCLUSION

A higher power of discrimination is obtained by combining more than one biomarker. However, the multimarker candidates identified in this study need further assessment.

Place, publisher, year, edition, pages
European Society of ClinicalMicrobiology and Infectious Diseases (ESCMID), 2015
National Category
Microbiology in the medical area
Research subject
Infection Biology
Identifiers
urn:nbn:se:his:diva-10873 (URN)
Conference
25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015
Funder
Knowledge Foundation
Available from: 2015-04-29 Created: 2015-04-29 Last updated: 2018-11-15Bibliographically approved
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