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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)31403210 (PubMedID)
Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-08-23Bibliographically 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) Epub ahead of print
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: 2019-06-20Bibliographically 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
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 1435-4373Article in journal (Refereed) Epub ahead of print
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)31396832 (PubMedID)
Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-08-23Bibliographically 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
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: 2019-06-20Bibliographically 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
Brüggemann, H., Poehlein, A., Brzuszkiewicz, E., Scavenius, C., Enghild, J. J., Al-Zeer, M. A., . . . Söderquist, B. (2019). Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay. Frontiers in Microbiology, 10, Article ID 478.
Open this publication in new window or tab >>Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay
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2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 478Article in journal (Refereed) Published
Abstract [en]

The slow-growing, anaerobic, coagulase-negative species Staphylococcus saccharolyticus is found on human skin and in clinical specimens but its pathogenic potential is unclear. Here, we investigated clinical isolates and sequenced the genomes of seven strains of S. saccharolyticus. Phylogenomic analyses showed that the closest relative of S. saccharolyticus is Staphylococcus capitis with an average nucleotide identity of 80%. Previously sequenced strains assigned to S. saccharoiyticus are misclassified and belong to S. capitis. Based on single nucleotide polymorphisms of the core genome, the population of S. saccharolyticus can be divided into two clades that also differ in a few larger genomic islands as part of the flexible genome. An unexpected feature of S. saccharolyticus is extensive genome decay, with over 300 pseudogenes, indicating ongoing reductive evolution. Many genes of the core metabolism are not functional, rendering the species auxotrophic for several amino acids, which could explain its slow growth and need for fastidious growth conditions. Secreted proteins of S. saccharolyticus were determined; they include stress response proteins such as heat and oxidative stress-related factors, as well as immunodominant staphylococcal surface antigens and enzymes that can degrade host tissue components. The strains secrete lipases and a hyaluronic acid lyase. Hyaluronidase as well as urease activities were detected in biochemical assays, with Glade-specific differences. Our study revealed that S. saccharolyticus has adapted its genome, possibly due to a recent change of habitat; moreover, the data imply that the species has tissue-invasive potential and might cause prosthetic joint infections.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
Staphylococcus, Staphylococcus saccharolyticus, coegulase-negative staphylococci, prosthetic joint infection, slow-growing bacteria, genome, genome decay, hyaluronic acid lyase
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-73323 (URN)10.3389/fmicb.2019.00478 (DOI)000460970900001 ()
Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-03-26Bibliographically approved
Luhr, R., Cao, Y., Söderquist, B. & Cajander, S. (2019). 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. Critical Care, 23, Article ID 241.
Open this publication in new window or tab >>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 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 241Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Severe sepsis, Septic shock, Mortality, Randomised controlled trial, Meta-analysis
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-75206 (URN)10.1186/s13054-019-2528-0 (DOI)000473735400001 ()31269976 (PubMedID)2-s2.0-85068603092 (Scopus ID)
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
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: 2018-09-13Bibliographically approved
Wistrand, C., Söderquist, B., Falk-Brynhildsen, K. & Nilsson, U. (2018). Exploring bacterial growth and recolonization after preoperative hand disinfection and surgery between operating room nurses and non-health care workers: a pilot study. BMC Infectious Diseases, 18(1), Article ID 466.
Open this publication in new window or tab >>Exploring bacterial growth and recolonization after preoperative hand disinfection and surgery between operating room nurses and non-health care workers: a pilot study
2018 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, no 1, article id 466Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: To prevent cross infection the surgical team perform preoperative hand disinfection before dressed in surgical gowns and gloves. Preoperative hand disinfection does not make hands sterile and the surgical glove cuff end has been regarded as a weak link, since it is not a liquid-proof interface. The aims were to investigate if there were differences in bacterial growth and recolonization of hands between operating room nurses and non-health care workers as well as to investigate if bacterial growth existed at the surgical glove cuff end during surgery.

METHODS: This pilot project was conducted as an exploratory comparative clinical trial. Bacterial cultures were taken from the glove and gown interface and at three sites of the hands of 12 operating room nurses and 13 non-health care workers controls directly after preoperative hand disinfection and again after wearing surgical gloves and gowns. Colony forming units were analysed with Mann-Whitney U test and Wilcoxon Sign Ranks test comparing repeated measurements. Categorical variables were evaluated with chi-square test or Fisher's exact test.

RESULTS: Operating room nurses compared to non-health care workers had significant higher bacterial growth at two of three culture sites after surgical hand disinfection. Both groups had higher recolonization at one of the three culture sites after wearing surgical gloves. There were no differences between the groups in total colony forming units, that is, all sampling sites. Five out of 12 of the operating room nurses had bacterial growth at the glove cuff end and of those, four had the same bacteria at the glove cuff end as found in the cultures from the hands. Bacteria isolated from the glove cuff were P. acnes, S. warneri, S. epidermidis and Micrococcus species, the CFU/mL ranged from 10 to 40.

CONCLUSIONS: There were differences in bacterial growth and re-colonization between the groups but this was inconclusive. However, bacterial growth exists at the glove cuff and gown interface, further investigation in larger study is needed, to build on these promising, but preliminary, findings.

TRIAL REGISTRATION: Trial registration was performed prospectively at Research web (FOU in Sweden, 117,971) 14/01/2013, and retrospectively at ClinicalTrials.gov ( NCT02359708 ). 01/27/2015.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Bacterial growth, Bacterial re-colonization, Cross infection, Hand disinfection, Intraoperative, Preoperative, Surgery, Surgical gloves, Surgical site infections
National Category
Infectious Medicine Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:oru:diva-69132 (URN)10.1186/s12879-018-3375-3 (DOI)000444938900001 ()30223772 (PubMedID)2-s2.0-85053382679 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro County Council  

Örebro University, Sweden 

Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-10-04Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5939-2932

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