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Rasmussen, G., Asfaw Idosa, B., Monecke, S., Bäckman, A., Strålin, K., Särndahl, E. & Söderquist, B. (2019). Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteremia. Microbiology and immunology
Open this publication in new window or tab >>Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteremia
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2019 (English)In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421Article in journal (Refereed) Epub ahead of print
Abstract [en]

The inflammasome is a multiprotein complex that mediates caspase-1 activation with subsequent maturation of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. The present study therefore aimed to investigate NLRP3 inflammasome activity in 20 S. aureus bacteremia patients, by repeated measurement during the first week of bacteremia, compared with controls. Caspase-1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (Fluorescent Labelled Inhibitor of Caspase-1), while IL-1β and IL-18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, mRNA expression of NLRP3, CASP1 (pro-caspase-1) and IL1B (pro-IL-1β) was analyzed by qPCR. We found induced caspase-1 activity in innate immune cells with subsequent release of IL-18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial inter-individual variation in caspase-1 activity between S. aureus bacteremia patients. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in S. aureus bacteremia could provide support in the effort to optimize management and treatment of each individual patient.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2019
Keywords
Caspase-1, NLRP3, Staphylococcus aureus, sepsis
National Category
Immunology
Identifiers
urn:nbn:se:oru:diva-75829 (URN)10.1111/1348-0421.12738 (DOI)000490350100001 ()31403210 (PubMedID)
Note

Funding Agencies:

Nyckelfonden in Region Örebro County, Sweden  

Region Örebro County's Research Committee, Sweden  

ALF research funding in Region Örebro County, Sweden  

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-11-15Bibliographically approved
Liew-Littorin, C., Brüggemann, H., Davidsson, S., Nilsdotter-Augustinsson, Å., Hellmark, B. & Söderquist, B. (2019). Clonal diversity of Cutibacterium acnes (formerly Propionibacterium acnes) in prosthetic joint infections. Anaerobe, 59, 54-60
Open this publication in new window or tab >>Clonal diversity of Cutibacterium acnes (formerly Propionibacterium acnes) in prosthetic joint infections
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2019 (English)In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 59, p. 54-60Article in journal (Refereed) Published
Abstract [en]

Prosthetic joint infections (PJIs) are rare but feared complications following joint replacement surgery. Cutibacterium acnes is a skin commensal that is best known for its role in acne vulgaris but can also cause invasive infections such as PJIs. Some phylotypes might be associated with specific diseases, and recently, a plasmid was detected that might harbour important virulence genes. In this study, we characterized C. acnes isolates from 63 patients with PJIs (n=140 isolates) and from the skin of 56 healthy individuals (n=56 isolates), using molecular methods to determine the phylotype and investigate the presence of the plasmid. Single-locus sequence typing and a polymerase chain reaction designed to detect the plasmid were performed on all 196 isolates. No statistically significant differences in sequence types were seen between the two study groups indicating that the C. acnes that causes PJIs originates from the patients own normal skin microbiota. Of the 27 patients with multiple tissue samples, 19 displayed the same sequence types among all their samples. Single-locus sequence typing identified different genotypes among consecutive C. acnes isolates from four patients with recurrent infections. The plasmid was found among 17 isolates distributed in both groups, indicating that it might not be a marker for virulence regarding PJIs. Patients presenting multiple sequence types in tissue samples may represent contamination or a true polyclonal infection due to C. acnes.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Cutibacterium acnes, Propionibacterium acnes, plasmid, prosthetic joint infection, single-locus sequence typing (SLST)
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-74235 (URN)10.1016/j.anaerobe.2019.04.011 (DOI)31075312 (PubMedID)
Available from: 2019-05-14 Created: 2019-05-14 Last updated: 2019-11-13Bibliographically approved
Fagerström, A., Mölling, P., Khan, F. A., Sundqvist, M., Jass, J. & Söderquist, B. (2019). Comparative distribution of extended-spectrum beta-lactamase-producing Escherichia coli from urine infections and environmental waters. PLoS ONE, 14(11), Article ID e0224861.
Open this publication in new window or tab >>Comparative distribution of extended-spectrum beta-lactamase-producing Escherichia coli from urine infections and environmental waters
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 11, article id e0224861Article in journal (Refereed) Published
Abstract [en]

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have been reported in natural environments, and may be released through wastewater. In this study, the genetic relationship between ESBL-producing E. coli collected from patient urine samples (n = 45, both hospitalized patients and out-patients) and from environmental water (n = 82, from five locations), during the same time period, was investigated. Three independent water samples were collected from the municipal wastewater treatment plant, both incoming water and treated effluent water; the receiving river and lake; and a bird sanctuary near the lake, on two different occasions. The water was filtered and cultured on selective chromID ESBL agar plates in order to detect and isolate ESBL-producing E. coli. Illumina whole genome sequencing was performed on all bacterial isolates (n = 127). Phylogenetic group B2 was more common among the clinical isolates than the environmental isolates (44.4% vs. 17.1%, p < 0.01) due to a significantly higher prevalence of sequence type (ST) 131 (33.3% vs. 13.4%, p < 0.01). ST131 was, however, one of the most prevalent STs among the environmental isolates. There was no significant difference in diversity between the clinical isolates (DI 0.872 (0.790-0.953)) and the environmental isolates (DI 0.947 (0.920-0.969)). The distribution of ESBL genes was similar: blaCTX-M-15 dominated, followed by blaCTX-M-14 and blaCTX-M-27 in both the clinical (60.0%, 8.9%, and 6.7%) and the environmental isolates (62.2%, 12.2%, and 8.5%). Core genome multi-locus sequence typing showed that five environmental isolates, from incoming wastewater, treated wastewater, Svartån river and Hjälmaren lake, were indistinguishable or closely related (≤10 allele differences) to clinical isolates. Isolates of ST131, serotype O25:H4 and fimtype H30, from the environment were as closely related to the clinical isolates as the isolates from different patients were. This study confirms that ESBL-producing E. coli are common in the aquatic environment even in low-endemic regions and suggests that wastewater discharge is an important route for the release of ESBL-producing E. coli into the aquatic environment.

Place, publisher, year, edition, pages
PLOS, 2019
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-77879 (URN)10.1371/journal.pone.0224861 (DOI)31697734 (PubMedID)
Available from: 2019-11-14 Created: 2019-11-14 Last updated: 2019-11-14Bibliographically approved
Stenmark, B., Hellmark, B. & Söderquist, B. (2019). Genomic analysis of Staphylococcus capitis isolated from blood cultures in neonates at a neonatal intensive care unit in Sweden. European Journal of Clinical Microbiology and Infectious Diseases, 38(11), 2069-2075
Open this publication in new window or tab >>Genomic analysis of Staphylococcus capitis isolated from blood cultures in neonates at a neonatal intensive care unit in Sweden
2019 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 11, p. 2069-2075Article in journal (Refereed) Published
Abstract [en]

Emergence of a genetically distinct, multidrug-resistant Staphylococcus capitis clone (NRCS-A) present in neonatal intensive care units has recently been extensively reported. The aims of the present study were to investigate which clones of S. capitis isolated from blood in a Swedish neonatal intensive care unit (NICU) have been present since 1987 and to investigate whether the NRCS-A clone has disseminated in Sweden. All S. capitis isolates from blood cultures of neonates (≤ 28 days of age) between 1987 and 2017 (n = 46) were whole-genome sequenced, and core genome multilocus sequence typing (cgMLST) was performed. Single-nucleotide polymorphism (SNP)-based phylogenetic relationships between the S. capitis isolates and in silico predictions of presence of genetic traits specific to the NRCS-A clone were identified. Furthermore, antibiotic susceptibility testing, including screening for heterogeneous glycopeptide-intermediate resistance, was performed. Thirty-five isolates clustered closely to the isolates previously determined as belonging to the NRCS-A clone and had fewer than 81 core genome loci differences out of 1063. Twenty-one of these isolates were multidrug resistant. The NRCS-A clone was found in 2001. Six pairs of isolates had differences of fewer than two SNPs. Genetic traits associated with the NRCS-A clone such as nsr, ebh, tarJ, and CRISPR were found in all 35 isolates. The increasing incidence of S. capitis blood cultures of neonates is predominantly represented by the NRSC-A clone at our NICU in Sweden. Furthermore, there were indications of transmission between cases; adherence to basic hygiene procedures and surveillance measures are thus warranted.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Coagulase negative staphylococci, NRCS-A clone, Neonatal intensive care unit, S. capitis, Whole-genome sequencing
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-75811 (URN)10.1007/s10096-019-03647-3 (DOI)000491944700010 ()31396832 (PubMedID)2-s2.0-85070296964 (Scopus ID)
Note

Funding Agencies:

Örebro County Research Council 

Örebro University 

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-11-15Bibliographically approved
Tevell, S., Christensson, B., Nilsdotter-Augustinsson, Å., Rydén, C., Ryding, U., Söderquist, B. & Åkerlund, B. (2019). Handläggning av infektioner vid ortopediska implantat en utmaning för vården [Treatment of orthopedic implant-associated infections]. Läkartidningen, 116(43), Article ID FR6C.
Open this publication in new window or tab >>Handläggning av infektioner vid ortopediska implantat en utmaning för vården [Treatment of orthopedic implant-associated infections]
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2019 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, no 43, article id FR6CArticle, review/survey (Refereed) Published
Abstract [en]

The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed. The study group emphasizes that implant associated infections are challenging and requires multidisciplinary cooperation, including, but not limited to, specialists in orthopedic surgery, infectious diseases, clinical microbiology and radiology for optimal treatment results. All aspects of the clinical management are equally important; selecting the optimal antibiotic prophylaxis in arthroplasty as well as fracture surgery, early diagnosis of infection, adequate treatment, follow-up, and finally a structured evaluation of outcome. Profound and updated knowledge of treatment of biofilm related infection is necessary to achieve optimal results in patients with implant-associated infections. Future challenges include improved decision support for combining surgical treatment with selection of proper antibiotics, as well as management of antibiotic resistance, drug-drug interactions and adverse effects of antibiotic treatment.

Place, publisher, year, edition, pages
Läkartidningen Förlag AB, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77620 (URN)31638706 (PubMedID)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
Sagerfors, S., Lindblad, B. E. & Söderquist, B. (2019). Infectious keratitis: isolated microbes and their antibiotic susceptibility pattern during 2004-2014 in Region Örebro County, Sweden. Acta Ophthalmologica
Open this publication in new window or tab >>Infectious keratitis: isolated microbes and their antibiotic susceptibility pattern during 2004-2014 in Region Örebro County, Sweden
2019 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768Article in journal (Refereed) Epub ahead of print
Abstract [en]

PURPOSE: To describe predisposing risk factors, causative microorganisms and their antibiotic susceptibility patterns in infectious keratitis during an 11-year period in Region Örebro County, Sweden.

METHODS: This is a descriptive study conducted as a retrospective audit of clinical records. Patients who received treatment for infectious keratitis at any of the three ophthalmological departments within Region Örebro County, Sweden, between 2004 and 2014 were included if they fulfilled the predefined criteria for infectious keratitis. Data regarding culture results, antibiotic susceptibility pattern and risk factors for infectious keratitis were obtained from medical records and microbiological reports.

RESULTS: In total, 398 episodes of infectious keratitis in 392 patients were included, and 285 were culture positive. The most common predisposing risk factor was contact lens wear (45%). Coagulase-negative staphylococci (39.6%) was the most commonly isolated type of organism. Staphylococcus aureus (15.1%) followed by Moraxella spp. (7.4%) and Pseudomonas aeruginosa (6.7%) were among the most common isolated bacteria not considered to be commensal. Reduced susceptibility to fluoroquinolones was observed in five of 43 S. aureus isolates and in four of nine Streptococcus pneumoniae isolates.

CONCLUSION: The most common predisposing risk factor for keratitis was contact lens wear. Among the most common microbes, not considered to be exclusively commensals, isolated from the cornea in microbial keratitis were S. aureus, Moraxella spp. and P. aeruginosa. The antibiotic susceptibility patterns showed low proportion of resistance. Empiric treatment of suspected infectious keratitis with topical fluoroquinolones and chloramphenicol might be considered in a setting like ours pending culture results.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
Antibiotic susceptibility, keratitis, microbes
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77026 (URN)10.1111/aos.14256 (DOI)31580009 (PubMedID)
Available from: 2019-10-07 Created: 2019-10-07 Last updated: 2019-10-07Bibliographically approved
Khan, F. A., Söderquist, B. & Jass, J. (2019). Prevalence and Diversity of Antibiotic Resistance Genes in Swedish Aquatic Environments Impacted by Household and Hospital Wastewater. Frontiers in Microbiology, 10, Article ID 688.
Open this publication in new window or tab >>Prevalence and Diversity of Antibiotic Resistance Genes in Swedish Aquatic Environments Impacted by Household and Hospital Wastewater
2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 688Article in journal (Refereed) Published
Abstract [en]

Antibiotic-resistant Enterobacteriaceae and non-lactose fermenting Gram-negative bacteria are a major cause of nosocomial infections. Antibiotic misuse has fueled the worldwide spread of resistant bacteria and the genes responsible for antibiotic resistance (ARGs). There is evidence that ARGs are ubiquitous in non-clinical environments, especially those affected by anthropogenic activity. However, the emergence and primary sources of ARGs in the environment of countries with strict regulations for antibiotics usage are not fully explored. The aim of the present study was to evaluate the repertoire of ARGs of culturable Gram-negative bacteria from directionally connected sites from the hospital to the wastewater treatment plant (WWTP), and downstream aquatic environments in central Sweden. The ARGs were detected from genomic DNA isolated from a population of selectively cultured coliform and Gram-negative bacteria using qPCR. The results show that hospital wastewater was a reservoir of several class B beta-lactamase genes such as bla(IMP)(-1), bla(IMP)(-2), and bla(OXA-23), however, most of these genes were not observed in downstream locations. Moreover, beta-lactamase genes such as bla(OXA-48), bla(CDX-M-8), and bla(SFC-1), bla(VIM-1), and bla(VIM-13) were detected in downstream river water but not in the WWTP. The results indicate that the WWTP and hospital wastewaters were reservoirs of most ARGs and contribute to the diversity of ARGs in associated natural environments. However, this study suggests that other factors may also have minor contributions to the prevalence and diversity of ARGs in natural environments.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
carbapenemase, urban wastewater, surface water, enterobacteriaceae, VIM-1, extended-spectrum beta-lactamase, antimicrobial resistance gene co-occurrence
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-73758 (URN)10.3389/fmicb.2019.00688 (DOI)000463403600001 ()
Funder
Swedish Research Council Formas, 219-2014-837Knowledge Foundation, 20150084
Note

Funding Agencies:

Nyckelfonden at Örebro University Hospital  

Örebro University 

Available from: 2019-04-16 Created: 2019-04-16 Last updated: 2019-04-16Bibliographically approved
Tevell, S., Baig, S., Nilsdotter-Augustinsson, Å., Stegger, M. & Söderquist, B. (2019). Same Organism, Different Phenotype: Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?. Journal of bone and joint infection, 4(1), 16-19
Open this publication in new window or tab >>Same Organism, Different Phenotype: Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?
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2019 (English)In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 4, no 1, p. 16-19Article in journal (Refereed) Published
Abstract [en]

In current diagnostic criteria for implant-associated bone- and joint infections, phenotypically identical low-virulence bacteria in two intraoperative cultures are usually required. Using whole-genome sequencing, we have further characterized three phenotypically different Staphylococcus capitis isolated from one prosthetic joint infection, highlighting the challenges in defining microbiological criteria for low-virulence prosthetic joint infections.

Place, publisher, year, edition, pages
British Editorial Society of Bone and Joint Surger, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77484 (URN)10.7150/jbji.30256 (DOI)30755843 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved
Magnusson, C., Stegger, M., Hellmark, B., Stenmark, B. & Söderquist, B. (2019). Staphylococcus aureus isolates from nares of orthopaedic patients in Sweden are mupirocin susceptible [Letter to the editor]. Infectious Diseases, 51(6), 475-478
Open this publication in new window or tab >>Staphylococcus aureus isolates from nares of orthopaedic patients in Sweden are mupirocin susceptible
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2019 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 6, p. 475-478Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-73786 (URN)10.1080/23744235.2019.1593500 (DOI)000466685100001 ()30985251 (PubMedID)2-s2.0-85064501385 (Scopus ID)
Note

Funding Agency:

Nyckelfonden at Örebro University Hospital  OLL-248651

Available from: 2019-04-16 Created: 2019-04-16 Last updated: 2019-10-14Bibliographically approved
Taha, L., Stegger, M. & Söderquist, B. (2019). Staphylococcus lugdunensis: antimicrobial susceptibility and optimal treatment options. European Journal of Clinical Microbiology and Infectious Diseases, 38(8), 1449-1455
Open this publication in new window or tab >>Staphylococcus lugdunensis: antimicrobial susceptibility and optimal treatment options
2019 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 8, p. 1449-1455Article in journal (Refereed) Published
Abstract [en]

Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that of S. aureus. Unlike other CoNS, S. lugdunensis remains susceptible to most antibiotics. The resistance to penicillin varies widely (range, 15-87% worldwide), whereas methicillin resistance is still rare. We aimed to evaluate treatment options for infections caused by S. lugdunensis and more specifically to investigate whether penicillin G could be a better treatment choice than oxacillin. Susceptibility testing was performed using the disc diffusion method for penicillin G, cefoxitin, trimethoprim/sulfamethoxazole, erythromycin, clindamycin, gentamicin, norfloxacin, fusidic acid, rifampicin, and fosfomycin. Isolates susceptible to penicillin G were further tested with a gradient test for penicillin G and oxacillin. Of the 540 clinical isolates tested, 74.6% were susceptible to penicillin G. Among these penicillin-susceptible isolates, the MIC50 and MIC90 values for penicillin G were threefold lower than that for oxacillin. A majority of the isolates were susceptible to all other antibiotics tested. Breakpoints for fosfomycin have not yet been defined, and so no conclusions could be drawn. Two isolates were resistant to cefoxitin and carried the mecA gene; whole-genome sequencing revealed that both harbored the SCCmec element type IVa(2B). S. lugdunensis isolated in Sweden were susceptible to most tested antibiotics. Penicillin G may be a more optimal treatment choice than oxacillin. Although carriage of the mecA gene is rare among S. lugdunensis, it does occur.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Staphylococcus lugdunensis, Antibiotic susceptibility testing, Penicillin G, Oxacillin
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-75715 (URN)10.1007/s10096-019-03571-6 (DOI)000476492200008 ()31144243 (PubMedID)2-s2.0-85066805371 (Scopus ID)
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved
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