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Cajander, S., Rasmussen, G., Tina, E., Magnuson, A., Söderquist, B., Källman, J. & Strålin, K. (2018). Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection. PLoS ONE, 13(2), Article ID e0192883.
Open this publication in new window or tab >>Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192883Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-65287 (URN)10.1371/journal.pone.0192883 (DOI)000425604300071 ()29466395 (PubMedID)2-s2.0-85042254936 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council  

ALF research funding (Örebro University)  

Nyckelfonden (Örebro University Hospital)  

ALF research funding (Örebro) 

Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-21Bibliographically approved
Stenmark, B., Hellmark, B. & Söderquist, B. (2018). Increase of S. capitis in neonates with bacteremia in Sweden due to the emergence of a multidrug-resistant clone. In: : . Paper presented at 28th European Congress of Clinical Microbiology and Infectious Diseases, Madrid, Spain, 21-24 April, 2018.
Open this publication in new window or tab >>Increase of S. capitis in neonates with bacteremia in Sweden due to the emergence of a multidrug-resistant clone
2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Background: Staphylococcus capitis has traditionally been considered a commensal due to its low pathogenicity in healthy adults; however, it has been shown to cause 20% of all cases of neonatal sepsis in neonatal intensive care units (NICUs). In addition, S. capitis strains with reduced susceptibility to last line anti-staphylococcal agents such as vancomycin and linezolid are emerging in NICUs. The aim of this study was to characterize S. capitis isolated from blood in a Swedish NICU and to investigate if the multidrug-resistant clone NRCS-A has disseminated in Sweden.

Materials/methods: All S. capitis isolates from neonatal blood cultures collected at Örebro University Hospital during 1987 to the 1st of March 2017 (n=42), were included. Several more episodes of neonatal sepsis with growth of coagulase-negative staphylococci were registered during this time period but probably considered as contaminants and therefore not preserved. Antibiotic susceptibility testing was performed using standardized disc diffusion method on cefoxitin, fusidic acid, clindamycin, erythromycin, gentamicin, rifampicin, trimethroprim/sulfamethoxazole and norfloxacin. Isolates resistant to ≥3 antibiotics were defined as multidrug-resistant. The isolates were whole genome sequenced using the Nextera XT kit (Illumina) on a MiSeq (Illumina). Single nucleotide polymorphisms found with the online tool REALPHY 1.12 in the alignments of shared homologous sites with the reference (the S. capitis NRCS-A strain CR01) were used to create phylogenetic trees.

Results: Seventeen isolates out of the 42 isolates (40%) were multidrug-resistant (resistant to fusidic acid, cefoxitin and gentamicin) and 33 out of the 42 isolates (79%) clustered with the multi-resistant NRCS-A clone (Figure 1). The earliest isolate within the NRCS-A cluster was from 2001.

Conclusions: Although prevalent since 2001, the increase of S. capitis in neonates with bacteremia since 2010 in Örebro county is mainly due to the dissemination of the multidrug-resistant NRCS-A clone and therefore warrants increased surveillance of the epidemiology and etiology of neonatal sepsis to prevent the spread of this clone.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-67258 (URN)
Conference
28th European Congress of Clinical Microbiology and Infectious Diseases, Madrid, Spain, 21-24 April, 2018
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-06-14Bibliographically approved
Sagerfors, S., Lindblad, B. E. & Söderquist, B. (2018). Infectious keratitis: Isolated microbes and their antibiotic susceptibility pattern during 11 years in Region Örebro County, Sweden. In: : . Paper presented at ARVO 2018(The Association for Research in Vision and Ophthalmology), Honolulu, Hawaii, USA, April 28-3 May, 2010.
Open this publication in new window or tab >>Infectious keratitis: Isolated microbes and their antibiotic susceptibility pattern during 11 years in Region Örebro County, Sweden
2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-67267 (URN)
Conference
ARVO 2018(The Association for Research in Vision and Ophthalmology), Honolulu, Hawaii, USA, April 28-3 May, 2010
Available from: 2018-06-15 Created: 2018-06-15 Last updated: 2018-06-15Bibliographically approved
Månsson, E., Sahdo, B., Nilsdotter-Augustinsson, Å., Särndahl, E. & Söderquist, B. (2018). Lower activation of caspase-1 by Staphylococcus epidermidis isolated from prosthetic joint infections compared to commensals. Journal of bone and joint infection, 3(1), 10-14
Open this publication in new window or tab >>Lower activation of caspase-1 by Staphylococcus epidermidis isolated from prosthetic joint infections compared to commensals
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2018 (English)In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 10-14Article in journal (Refereed) Published
Abstract [en]

Nosocomial sequence types of Staphylococcus epidermidis dominate in prosthetic joint infections. We examined caspase-1 activation in human neutrophils after incubation with Staphylococcus epidermidis isolated from prosthetic joint infections and normal skin flora. Active caspase-1 was lower after incubation with isolates from prosthetic joint infections than after incubation with commensal isolates. Both host and isolate dependent differences in active caspase-1 were noted. Our results indicate that there might be a host-dependent incapacity to elicit a strong caspase-1 response towards certain strains of S. epidermidis. Further experiments with a larger number of individuals are warranted.

Place, publisher, year, edition, pages
IVYSPRING, 2018
Keyword
Staphylococcus epidermidis, caspase-1, neutrophils, prosthetic joint infections, host-pathogen interaction
National Category
Medical and Health Sciences Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-65927 (URN)10.7150/jbji.21567 (DOI)29545990 (PubMedID)
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-22Bibliographically approved
Brüggemann, H., Jensen, A., Nazipi, S., Aslan, H., Meyer, R. L., Poehlein, A., . . . Söderquist, B. (2018). Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors. Scientific Reports, 8, Article ID 266.
Open this publication in new window or tab >>Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 266Article in journal (Refereed) Published
Abstract [en]

Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-64519 (URN)10.1038/s41598-017-18661-8 (DOI)000419668400040 ()29321635 (PubMedID)2-s2.0-85040467514 (Scopus ID)
Note

Funding Agency:

Nyckelfonden at Örebro University Hospital, Sweden 

Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2018-01-25Bibliographically approved
Lindell, F., Söderquist, B., Sundman, K., Olaison, L. & Källman, J. (2018). Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases. European Journal of Clinical Microbiology and Infectious Diseases, 37(4), 765-771
Open this publication in new window or tab >>Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases
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2018 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 4, p. 765-771Article in journal (Refereed) Published
Abstract [en]

Propionibacterium spp. are a rare cause of infective endocarditis (IE). The diagnosis is difficult because the bacteria are slow-growing and growth in blood cultures is often misinterpreted as contamination from the skin flora. The aim of this study was to describe all cases of Propionibacterium spp. endocarditis in the Swedish national registry of IE. The registry was searched for all cases of IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical characteristics, treatment, and outcome were registered. A total of 51 episodes of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium spp. were identified, comprising 8% of cases of PVE during the study period. Almost all cases (n = 50) were male. The median time from surgery to diagnosis of IE was 3 years. Most patients were treated mainly with beta-lactams, partly in combination with aminoglycosides. Benzyl-penicillin was the most frequently used beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during treatment. IE caused by Propionibacterium spp. almost exclusively affects men with a prosthetic valve and findings of Propionibacterium spp. in blood cultures in such patients favors suspicion of a possible diagnosis of IE. In patients with prosthetic valves, prolonged incubation of blood cultures up to 14 days is recommended. The prognosis was favorable, although a majority of patients required cardiac surgery during treatment. Benzyl-penicillin should be the first-line antibiotic treatment option for IE caused by Propionibacterium spp.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-64849 (URN)10.1007/s10096-017-3172-8 (DOI)000428247300021 ()29380224 (PubMedID)2-s2.0-85041116111 (Scopus ID)
Available from: 2018-02-07 Created: 2018-02-07 Last updated: 2018-04-13Bibliographically approved
Salih, L., Tevell, S., Månsson, E., Nilsdotter-Augustinsson, Å., Hellmark, B. & Söderquist, B. (2018). Staphylococcus epidermidis isolates from nares and prosthetic joint infections are mupirocin susceptible. Journal of bone and joint infection, 3(1), 1-4
Open this publication in new window or tab >>Staphylococcus epidermidis isolates from nares and prosthetic joint infections are mupirocin susceptible
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2018 (English)In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 1-4Article in journal (Refereed) Published
Abstract [en]

The objective of the present study was to investigate the antibiotic susceptibility including mupirocin among Staphylococcus. epidermidis isolated from prosthetic joint infections (PJIs) (n=183) and nasal isolates (n=75) from patients intended to undergo prosthetic joint replacements. Susceptibility to mupirocin (used for eradication of nasal carriership of Staphylococcus aureus) was investigated by gradient test, and susceptibility to various other antimicrobial agents was investigated by disc diffusion test. All isolates, except three from PJIs and one from the nares, were fully susceptible to mupirocin. Multi-drug resistance (≥3 antibiotic classes) was found in 154/183 (84.2%) of the PJI isolates but only in 2/75 (2.7%) of the nares isolates, indicating that S. epidermidis causing PJIs do not originate from the nares.

Place, publisher, year, edition, pages
Ivyspring International Publisher, 2018
Keyword
Antibiotic susceptibility testing, Mupirocin, Prosthetic joint infections, Staphylococcus epidermidis
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-64047 (URN)10.7150/jbji.22459 (DOI)29291157 (PubMedID)
Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-01-12Bibliographically approved
Thunberg, U., Söderquist, B. & Hugosson, S. (2017). Bacterial findings in optimised sampling and characterisation of S. aureus in chronic rhinosinusitis. European Archives of Oto-Rhino-Laryngology, 274(1), 311-319
Open this publication in new window or tab >>Bacterial findings in optimised sampling and characterisation of S. aureus in chronic rhinosinusitis
2017 (English)In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 274, no 1, p. 311-319Article in journal (Refereed) Published
Abstract [en]

The bacterial spectrum in chronic rhinosinusitis (CRS) is clinically relevant. This study aimed to compare two sampling techniques and to characterise Staphylococcus aureus isolated from CRS patients. Bacterial specimens were collected from the nares and maxillary sinus in 42 CRS patients and from the nares in 57 healthy controls. Maxillary sinus sampling was performed in two ways in each patient: with a cotton-tipped aluminium swab through the enlarged sinus ostium, and with a protected brush. S. aureus was characterised by DNA-sequencing of the repeat region of the S. aureus protein A gene, spa typing. The protected brush technique was superior to the cotton-tipped aluminium swab in reducing contamination rate. However, the two sampling methods were consistent in terms of clinically relevant bacterial findings, and the easy-to-handle cotton-tipped swab can still be recommended when culturing the maxillary sinus. Patients showed a significantly higher presence of S. aureus in the nares compared with healthy controls, and healthy controls showed a significantly higher presence of coagulase-negative staphylococci in the nares compared with patients. The spa types were identical for the nares and maxillary sinus in all patients except one. The sampling techniques showed equivalent results, indicating a low risk of unnecessary antibiotic treatment when using the easy-to-handle cotton-tipped aluminium swab. The high rate of identical spa types of S. aureus isolated from the nares and maxillary sinus of CRS patients might indicate colonisation of the maxillary sinus from the nares.

Place, publisher, year, edition, pages
Heidelberg, Germany: Springer, 2017
Keyword
Staphylococcus aureus, sinusitis, nasal polyps, sampling studies, bacterial typing
National Category
Clinical Laboratory Medicine Otorhinolaryngology
Identifiers
urn:nbn:se:oru:diva-51748 (URN)10.1007/s00405-016-4239-3 (DOI)000393599900039 ()27538736 (PubMedID)2-s2.0-84982255261 (Scopus ID)
Note

Funding Agency:

Research Committee of Orebro County Council

Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2017-10-18Bibliographically approved
Rasmussen, G., Cajander, S., Bäckman, A., Källman, J., Söderquist, B. & Strålin, K. (2017). Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia. Microbiology and immunology, 61(10), 442-451
Open this publication in new window or tab >>Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia
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2017 (English)In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 61, no 10, p. 442-451Article in journal (Refereed) Published
Abstract [en]

To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n=13) and those without sepsis (n=7) on any assessment day. However, patients with complicated SAB (n=14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n=6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Asia, 2017
Keyword
CD74, HLA-DRA, sepsis, Staphylococcus aureus
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-62068 (URN)10.1111/1348-0421.12533 (DOI)000412860400005 ()28862321 (PubMedID)2-s2.0-85032877412 (Scopus ID)
Note

Funding Agency:

Research Committee of Örebro County Council

Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2018-02-23Bibliographically approved
Söderquist, B., Björklund, S., Hellmark, B., Jensen, A. & Brüggemann, H. (2017). Finegoldia magna Isolated from Orthopedic Joint Implant-Associated Infections. Journal of Clinical Microbiology, 55(11), 3283-3291
Open this publication in new window or tab >>Finegoldia magna Isolated from Orthopedic Joint Implant-Associated Infections
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2017 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 55, no 11, p. 3283-3291Article in journal (Refereed) Published
Abstract [en]

The anaerobic Gram-positive coccus Finegoldia magna is a rare cause of infections of bone and joints. The aim of this study was to describe the microbiological and clinical characteristics of orthopedic implant-associated infections caused by F. magna We retrospectively analyzed samples consisting of anaerobic Gram-positive cocci and samples already identified as F. magna from patients with orthopedic infections. The isolates found were determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern was determined by Etest. Whole-genome sequencing (WGS) was performed. Clinical data were extracted from each patient's journal. In nine patients, orthopedic joint implant-associated infections were identified as being caused by F. magna The isolates were susceptible to most of the antibiotics tested, with the exception of rifampin and moxifloxacin in a few cases. Five of the nine infections were monomicrobial. The most common antibiotic used to treat the infection was penicillin V, but five of the nine patients received a combination of antibiotics. Eight patients underwent surgical treatment, with extraction of the implant performed in seven cases and reimplantation in only two cases. The WGS showed a relatively small core genome, with 126,647 single nucleotide polymorphisms identified within the core genome. A phylogenomic analysis revealed that the isolates clustered into two distinct clades. Orthopedic implant-associated infections caused by F. magna are rare, but the bacteria are generally susceptible to antibiotics. Despite this, surgical treatment combined with long-term antibiotics is often necessary. The WGS analysis revealed a high heterogeneity and suggested the existence of at least two different Finegoldia species.

Place, publisher, year, edition, pages
American Society for Microbiology, 2017
Keyword
Finegoldia magna, antibiotic susceptibility test, orthopedic implant-associated infections, prosthetic joint infections, whole-genome sequencing
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-62478 (URN)10.1128/JCM.00866-17 (DOI)000414356400019 ()28904182 (PubMedID)2-s2.0-85032443997 (Scopus ID)
Note

Funding agencies:

Nyckelfonden at Orebro University Hospital OLL-595951 

Danish Medical Research council DFF-1331-00241 

Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-01-03Bibliographically approved
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