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- Månsson, Emeli, 1978-
(författare)
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Molecular epidemiology of Staphylococcus epidermidis in prosthetic joint infections
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus epidermidis is ubiquitous in the human microbiota, but also an important pathogen in healthcare-associated infections, such as prosthetic joint infections (PJIs). In this thesis, aspects of the molecular epidemiology of S. epidermidis in PJIs were investigated with the aim of improving our understanding of the pre- and perioperative measures required to reduce the incidence of S. epidermidis PJIs.In Paper I, S. epidermidis retrieved from air sampling in the operating field during arthroplasty was characterized by multilocus sequence typing and antibiotic susceptibility testing. No isolates belonging to sequence types (STs) 2 and 215, previously associated with PJIs, were found in the air of the operating field. During air sampling, several Staphylococcus pettenkoferi isolates were identified, and as a spin-off of Paper I, the genomic relatedness of these isolates to S. pettenkoferi isolates from blood cultures was described in Paper II.In Paper III, genetic traits distinguishing S. epidermidis isolated from PJIs were determined using genome-wide association study accounting for population effects after whole-genome sequencing (WGS) of a population- based 10-year collection of S. epidermidis isolates from PJIs and of nasal isolates retrieved from patients scheduled for arthroplasty. Genes associated with antimicrobial agents used for prophylaxis in arthroplasty, i.e., beta-lactam antibiotics, aminoglycosides, and chlorhexidine, were associated with PJI origin. S. epidermidis from PJIs were dominated by the ST2a, ST2b, ST5, and ST215 lineages.In Paper IV, selective agar plates were used to investigate colonization with methicillin resistant S. epidermidis (MRSE) in patients scheduled for arthroplasty. MRSE were further characterized by WGS. A subset of patients was found to harbour PJI-associated S. epidermidis lineages in their microbiota before hospitalization, but no isolates belonging to the ST2a lineage nor any rifampicin-resistant isolates were retrieved.
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| 2. |
- Tevell, Staffan, 1975-
(författare)
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Staphylococcal prosthetic joint infections : similar, but still different
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococci constitute a major part of our commensal flora but are also the most common bacteria causing prosthetic joint infections (PJIs), a dreaded complication of arthroplasty surgery. However, not all staphylococci are the same. The virulent Staphylococcus aureus has the ability to cause severe disease such as bacteremia and infective endocarditis in previously healthy people, while the coagulase-negative staphylococci Staphylococcus epidermidis and Staphylococcus capitis rarely act as pathogens unless the patient is immunocompromised or has an implanted medical device, such as a prosthetic joint. This thesis accordingly explores similarities and differences between these three staphylococci in PJIs.S. capitis can cause early postinterventional and chronic PJIs, a finding that has not previously been described. Furthermore, its nosocomial NRCS-A outbreak sublineage, recently observed in neonatal intensive care units, is also present in adult PJIs. When comparing nasal and PJI isolates, the patterns differed between staphylococcal species. In S. capitis, the commensal and infecting strains were separated phylogenetically, while they clustered together for S. aureus. This may indicate diverse reservoirs and acquisition routes in PJIs caused by different staphylococcal species.Outcomes in early postinterventional PJIs were similar in S. capitis and S. aureus infections, with 70–80% achieving clinical cure. In S. aureus infections, no virulence genes were significantly associated with outcome. Although multidrug resistance (MDR) was rare in S. aureus, inability to use biofilm-active antibiotics was a risk factor for failure. However, in S. epidermidis and in the NRCS-A sublineage of S. capitis, MDR and glycopeptide heteroresistance were widespread, highlighting the challenge of antibiotic resistance in the treatment of PJIs.
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| 3. |
- Wildeman, Peter, 1975-, et al.
(författare)
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Effect of a national infection control programme in Sweden on prosthetic joint infection incidence following primary total hip arthroplasty : a cohort study
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Prosthetic joint infection (PJI) is a serious complication following total hip arthroplasty (THA) entailing increased mortality, decreased quality of life and high healthcare costs.The primary aim was to investigate whether the national project: Prosthesis Related Infections Shall be Stopped (PRISS) reduced PJI incidence after primary THA; the secondary aim was to evaluate other possible benefits of PRISS, such as shorter time to diagnosis.DESIGN: Cohort study.SETTING: In 2009, a nationwide, multidisciplinary infection control programme was launched in Sweden, PRISS, which aimed to reduce the PJI burden by 50%.PARTICIPANTS: We obtained data on patients undergoing primary THA from the Swedish Arthroplasty Registry 2012-2014, (n=45 723 patients, 49 946 THAs). Using personal identity numbers, this cohort was matched with the Swedish Prescribed Drug Registry. Medical records of patients with ≥4 weeks' antibiotic consumption were reviewed to verify PJI diagnosis (n=2240, 2569 THAs).RESULTS: The cumulative incidence of PJI following the PRISS Project was 1.2% (95% CI 1.1% to 1.3%) as compared with 0.9% (95% CI 0.8% to 1.0%) before. Cox regression models for the PJI incidence post-PRISS indicates there was no statistical significance difference versus pre-PRISS (HR 1.1 (95% CI 0.9 to 1.3)). There was similar time to PJI diagnosis after the PRISS Project 24 vs 23 days (p=0.5).CONCLUSIONS: Despite the comprehensive nationwide PRISS Project, Swedish PJI incidence was higher after the project and time to diagnosis remained unchanged. Factors contributing to PJI, such as increasing obesity, higher American Society of Anesthesiology class and more fractures as indications, explain the PJI increase among primary THA patients.
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| 4. |
- Cajander, Sara, 1980-
(författare)
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Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression.In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control.In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.
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| 6. |
- Luhr, Robert, et al.
(författare)
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Trends in sepsis mortality over time in randomised sepsis trials : a systematic literature review and meta-analysis of mortality in the control arm, 2002-2016
- 2019
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 23
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Forskningsöversikt (refereegranskat)abstract
- Background: Epidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends.To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis. The primary aim was to assess whether the mortality in sepsis trials has changed over time. The secondary aim was to investigate how many of the included trials could show efficacy of the studied intervention regarding 28-day mortality.Methods: We searched PubMed for RCTs enrolling patients with severe sepsis and septic shock, published between 2002 and 2016. The included trials were assessed for quality and sorted by date of first inclusion. A meta-analysis was performed to synthesise data from the individual sepsis trials.Results: Of 418 eligible articles, 44 RCTs on sepsis were included in the analysis, enrolling 13,315 patients in the usual care arm between 1991 and 2013. In this time period, mortality decreased by 0.42% annually (p=0.04) to give a total decline of 9.24%. In subgroup analyses with adjustments for APACHE II, SAPS II and SOFA scores, the observed time trend was not significant (p=0.45, 0.23 and 0.98 respectively). Only four of the included trials showed any efficacy with regard to mortality.Conclusions: Data from RCTs show a declining trend in 28-day mortality in severe sepsis and septic shock patients during the years from 1991 to 2013. However, when controlling for severity at study inclusion, there was no significant change in mortality over time. The number of trials presenting new treatment options was low.Trial registration: PROSPERO CRD42018091100. Registered 27 August 2018.
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