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  • 1.
    Andersson, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Holmbom, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 7, p. 1223-1234Article in journal (Refereed)
    Abstract [en]

    Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.

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  • 2.
    Balkhed Östholm, Åse
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Duration of travel-associated faecal colonisation with ESBL-producing Enterobacteriaceae - A one year follow-up study2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 10Article in journal (Refereed)
    Abstract [en]

    In a previous study, we found that 30% of individuals travelling outside Scandinavia acquired extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in their faecal flora. The aim of this study was to determine the duration of travel-associated faecal colonisation with ESBL-PE, to assess risk factors for prolonged colonisation and to detect changes in antibiotic susceptibility during prolonged colonisation.

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  • 3.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam; TRAC Sweden Vietnam, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    TRAC Sweden Vietnam, Vietnam; Karolinska Inst, Sweden.
    Minh Dien, Tran
    Vietnam Natl Childrens Hosp, Vietnam.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam; TRAC Sweden Vietnam, Vietnam.
    Larsson, Mattias
    TRAC Sweden Vietnam, Vietnam; Karolinska Inst, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC Sweden Vietnam, Vietnam.
    Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital2019In: Antimicrobial Resistance and Infection Control, E-ISSN 2047-2994, Vol. 8, no 1, article id 156Article in journal (Refereed)
    Abstract [en]

    Background Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae. Methods In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015. Results Aside from the carbapenem resistance gene bla(KPC-2), which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone. Conclusions The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones.

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  • 4.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Olson, Linus
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Larsson, Mattias
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC, Sweden; TRAC, Vietnam.
    Insertion sequence transpositions and point mutations in mgrB causing colistin resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae from Vietnam2018In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 51, no 5, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem-and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 5.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Letter: High Prevalence of Heterogeneously Glycopeptide-Intermediate Coagulase-Negative Staphylococci in Sternal Wounds in ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol 60, issue 8, pp 5097-50982016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 8, p. 5097-5098Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 6.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoang, Ngoc Thi Bich
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Le, Ngai Kien
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Khu, Dung Thi Khanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    The Karolinska Institute, Stockholm, Sweden.
    Le, Hai Thanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Larsson, Mattias
    The Karolinska Institute, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and bla(OXA-48) isolated at a paediatric hospital in Vietnam2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 4, p. 1100-1102Article in journal (Other academic)
    Abstract [en]

    n/a

  • 7.
    Crisci, Elisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Rondahl, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergström, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Eriksson, Kristina
    University of Gothenburg, Gothenburg, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Complement opsonization promotes HSV-2 infection of human dendritic cells2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed)
    Abstract [en]

    Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

    IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

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  • 8.
    Cronhjort, Samuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Microbiology, Jönköping, Sweden.
    Karlsson, Linda
    Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
    Thelaus, Johanna
    Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
    Sjödin, Andreas
    Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Microbiology, Jönköping, Sweden.
    The Tick-Borne Diseases STING study: Real-time PCR analysis of three emerging tick-borne pathogens in ticks that have bitten humans in different regions of Sweden and the Aland islands, Finland2019In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 9, no 1, article id 1683935Article in journal (Refereed)
    Abstract [en]

    A milder climate has during the last decade contributed to an increased density and spreading of ixodid ticks, thus enhancing their role as emerging vectors for pathogenic microorganisms in northern Europe. It remains unclear if they contribute to the occurrence of infections caused by the bacteria Bartonella spp., Francisella tularensis subspecies holarctica and the parasite Toxoplasma gondii in Sweden and on the Åland islands, Finland. In this study, we want to improve understanding of the tick-borne transmission of these pathogens. Volunteers were recruited at primary healthcare centers. Ticks and blood samples were acquired from participants recruited in 2008 and 2009. Health questionnaires were completed, and medical records were acquired where applicable. Feeding time was estimated and screening of pathogens in the ticks was performed through real-time PCR. Ticks (n = 1849) were of mixed developmental stages: 76 larvae, 1295 nymphs, 426 adults and 52 undetermined. All analyzed ticks were considered negative for these pathogens since the CT-values were all below the detection limit for Bartonella spp. (1663 ticks), Francisella spp. (1849 ticks) and Toxoplasma gondii (1813 ticks). We assume that infections with these pathogens are caused by other transmission pathways within these regions of Sweden and the Åland islands, Finland.

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  • 9.
    Davies Forsman, Lina
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Niward, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hu, Yi
    Fudan Univ, Peoples R China; Fudan Univ, Peoples R China.
    Zheng, Rongrong
    Xiamen City Ctr Dis Control, Peoples R China.
    Zheng, Xubin
    Fudan Univ, Peoples R China.
    Ke, Ran
    Xiamen City Ctr Dis Control, Peoples R China.
    Cai, Weiping
    Xiamen City Ctr Dis Control, Peoples R China.
    Hong, Chao
    Xiamen City Ctr Dis Control, Peoples R China.
    Li, Yang
    Fudan Univ, Peoples R China.
    Gao, Yazhou
    Fudan Univ, Peoples R China.
    Werngren, Jim
    Publ Hlth Agcy Sweden, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Kuhlin, Johanna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Simonsson, Ulrika S. H.
    Uppsala Univ, Sweden.
    Eliasson, Erik
    Karolinska Univ Hosp, Sweden.
    Alffenaar, Jan-Willem
    Univ Groningen, Netherlands.
    Mansjo, Mikael
    Publ Hlth Agcy Sweden, Sweden.
    Hoffner, Sven
    Karolinska Inst, Sweden.
    Xu, Biao
    Fudan Univ, Peoples R China.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study2018In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 9, article id e023899Article in journal (Refereed)
    Abstract [en]

    Introduction Individualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB. Methods and analysis Adult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960. Ethics and dissemination This study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal. Trial registration number NCT02816931; Pre-results.

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  • 10.
    Dellgren, Linus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Högdahl, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Forsberg, Jon
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Phenotypic screening for quinolone resistance in Escherichia coli2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 9, p. 1765-1771Article in journal (Refereed)
    Abstract [en]

    Recent studies show that rectal colonization with low-level ciprofloxacin-resistant Escherichia coli (ciprofloxacin minimal inhibitory concentration (MIC) above the epidemiological cutoff point, but below the clinical breakpoint for resistance), i.e., in the range amp;gt; 0.06-0.5 mg/L is an independent risk factor for febrile urinary tract infection after transrectal ultrasound-guided biopsy (TRUS-B) of the prostate, adding to the other risk posed by established ciprofloxacin resistance in E. coli (MIC amp;gt; 0.5 mg/L) as currently defined. We aimed to identify the quinolone that by disk diffusion best discriminates phenotypic wild-type isolates (ciprofloxacin MIC amp;lt;= 0.06 mg/L) of E. coli from isolates with acquired resistance, and to determine the resistance genotype of each isolate. The susceptibility of 108 E. coli isolates was evaluated by ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, and pefloxacin disk diffusion and correlated to ciprofloxacin MIC (broth microdilution) using EUCAST methodology. Genotypic resistance was identified by PCR and DNA sequencing. The specificity was 100% for all quinolone disks. Sensitivity varied substantially, as follows: ciprofloxacin 59%, levofloxacin 46%, moxifloxacin 59%, nalidixic acid 97%, and pefloxacin 97%. We suggest that in situations where low-level quinolone resistance might be of importance, such as when screening for quinolone resistance in fecal samples pre-TRUS-B, a pefloxacin (S amp;gt;= 24 mm) or nalidixic acid (S amp;gt;= 19 mm) disk, or a combination of the two, should be used. In a setting where plasmid-mediated resistance is prevalent, pefloxacin might perform better than nalidixic acid.

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  • 11.
    Dettenkofer, Markus
    et al.
    University of Freiburg, Germany.
    Humphreys, Hilary
    Royal Coll Surg, Ireland; Beaumont Hospital, Ireland.
    Saenz, Henri
    European Soc Clin Microbiol and Infect Disease, Switzerland.
    Carlet, Jean
    Grp Hospital Paris St Joseph, France.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ruef, Christian
    Hirslanden Klin, Switzerland.
    Widmer, Andreas
    University of Basel Hospital, Switzerland.
    Wolkewitz, Martin
    University of Freiburg, Germany.
    Cookson, Barry
    UCL, England.
    Key priorities in the prevention and control of healthcare-associated infection: a survey of European and other international infection prevention experts2016In: Infection. Zeitschrift für Klinik und Therapie der Infektionen, ISSN 0300-8126, E-ISSN 1439-0973, Vol. 44, no 6, p. 719-724Article in journal (Refereed)
    Abstract [en]

    Purpose Prevention and control of healthcare-associated infection (HCAI) are important within and beyond Europe. However, it is unclear which areas are considered important by HCAI prevention and control professionals. This study assesses the priorities in the prevention and control of HCAI as judged by experts in the field. Methods A survey was conducted by the European Society of Clinical Microbiology and Infectious Diseases focussing on seven topics using SurveyMonkey (R). Through a newsletter distributed by email, about 5000 individuals were targeted throughout the world in February and March 2013. Participants were asked to rate the importance of particular topics from one (low importance) to ten (extraordinary importance), and there was no restriction on giving equal importance to more than one topic. Results A total of 589 experts from 86 countries participated including 462 from Europe (response rate: 11.8 %). Physicians accounted for 60 % of participants, and 57 % had ten or more years experience in this area. Microbial epidemiology/resistance achieved the highest priority scoring with 8.9, followed by surveillance 8.2, and decolonisation/disinfection/antiseptics with 7.9. Under epidemiology/resistance, highly resistant Gram-negative bacilli scored highest (9.0-9.2). The provision of computerised healthcare information systems for the early detection of outbreaks was accorded the top priority under surveillance. The prevention of surgical site and central line infections ranked highest under the category of specific HCAI and HCAI in certain settings. Differences between regions are described. Conclusion These findings reflect the concerns of experts in HCAI prevention and control. The results from this survey should inform national and international agencies on future action and research priorities.

  • 12.
    Edlund, Charlotta
    et al.
    Folkhälsomyndigheten, Sverige.
    Skoog, Gunilla
    Folkhälsomyndigheten, Sverige.
    Grape, Malin
    Folkhälsomyndigheten, Sverige.
    Hedin, Katarina
    FoU, Region Kronoberg, Sverige.
    Sundvall, Pär-Daniel
    FoU primärvård, Västra Götalandsregionen, Sverige.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Dags att fylla kunskapsluckor om antibiotikaanvändning i praxis2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 12Article in journal (Other academic)
  • 13.
    Flodin, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Communicable Disease and Infection Control.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 6Article in journal (Refereed)
  • 14.
    Fransen, Jian
    et al.
    Uppsala University, Sweden.
    Huss, Fredrik R. M.
    Uppsala University, Sweden; University of Uppsala Hospital, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Surveillance of antibiotic susceptibility in a Swedish Burn Center 1994-20122016In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, no 6, p. 1295-1303Article in journal (Refereed)
    Abstract [en]

    Patients with burn trauma are at risk for infections caused by antibiotic resistant bacteria (ABR) with subsequent increase in morbidity and mortality. As part of the Swedish strategic program against antibiotic resistance in intensive care (ICU-Strama), we have surveyed the distribution of species and ABR in isolates from patients admitted to a Swedish burn center at Linkoping University Hospital from 1994 through 2012. In an international comparison Strama has been successful in reducing the antibiotic consumption among animals and humans in primary care. The aim of this study was to investigate the antibiotic consumption pressure and resistance rates in a Swedish burn unit. Methods: Microbiology data, total body surface area (TBSA), patient days, and mortality were collected from a hospital database for all patients admitted to the Burn Center at the University Hospital of Linkoping from April 1994 through December 2012. Results: A total of 1570 patients were admitted with a mean annual admission rate of 83 patients (range: 57-152). 15,006 microbiology cultures (approximately 10 per patient) were collected during the study period and of these 4531 were positive (approximately 3 per patient). The annual mean total body surface area (TBSA) was 13.4% (range 9.5-18.5) with an annual mortality rate of 5.4% (range 1-8%). The MRSA incidence was 1.7% (15/866) which corresponds to an MRSA incidence of 0.34/1000 admission days (TAD). Corresponding figures were for Escherichia coli resistant to 3rd generation cephalosporins (ESBL phenotype) 8% (13/170) and 0.3/TAD, Klebsiella spp. ESBL phenotype 5% (6/134) and 0.14/TAD, carbapenem resistant Pseudomonas aeruginosa 26% (56/209) and 1.28/TAD, and carbapenem resistant Acinetobacter spp. 3% (2/64) and 0.04/TAD. Conclusions: Our results show a sustained low risk for MRSA and high, although not increasing, risk for carbapenem resistant P. aeruginosa. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.

  • 15.
    Grankvist, Anna
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Labbe Sandelin, Lisa
    Kalmar County Hospital, Sweden; Uppsala University, Sweden.
    Andersson, Jennie
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Wenneras, Christine
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden2015In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 21, no 8, p. 1462-1465Article in journal (Refereed)
    Abstract [en]

    The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.

  • 16.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hedman, Christina A
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Thyberg, Ingrid S M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life2019In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, no 6, p. 633-640Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls.

    METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples.

    RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments.

    CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

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  • 17.
    Gyllemark, Paula
    et al.
    Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Henningsson, Anna J.
    Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
    Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.2017In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.

    METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.

    RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.

    CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

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  • 18.
    Hamad, Tarza
    et al.
    University of Örebro, Sweden.
    Hellmark, Bengt
    University of Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Soderquist, Bo
    University of Örebro, Sweden.
    Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 12, p. 1055-1060Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S.epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S.epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.

  • 19.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Sepsis på akuten & IVA: Diagnostik och Antibiotikaterapi2017Collection (editor) (Other academic)
    Abstract [sv]

    Tredje upplagan av ”Sepsis på akuten och IVA” baseras delvis på SK-kursen med samma namn. Bokens innehall har dock utökats for att kunna ge praktiska anvisningar for diagnostik och terapi vid sepsis hos barn och vuxna med olika infektionsfokus. Sepsisboken ger också en inblick i vilka mekanismer som gör att sepsis snabbt kan bli ett livshotande tillstånd och vilka åtgärder som det ar mest bråttom med under de första timmarna av septisk chock. Kort tid mellan upptäckt av septisk chock och ratt insatt behandling sparar både organfunktion och liv. Modern intensivvård med monitorering av vätsketillförsel, vasokativa droger, respirator, dialys etc ar liksom ratt antibiotika i ratt dos en förutsättning for att kunna radda en patient med septisk chock. For att kunna ge ratt antibiotika kravs kunskap om vilka bakterier som ar vanligast vid olika typer av infektioner och deras antibiotikakänslighet. Ett kapitel i denna bok agnas därför at resistensläget i blododlingar från svenska patienter.

    Patienter som har nedsatt njurfunktion löper större risk for felaktig dosering av antimikrobiella läkemedel och behandlingsmisslyckande varför boken innehåller flera tabeller med doseringsanvisningar vid nedsatt njurfunktion och dialys. Ett kapitel agnas at handläggning av allvarliga bakteriella infektioner hos barn eftersom barn reagerar något annorlunda an vuxna vid sepsis, S. aureus ar vanligare och barn har en delvis annorlunda behandlingsalgoritm. Barn med immunsuppression berörs också och det ar ett kapitel om allvarliga infektioner hos vuxna patienter med neutropeni. Ett separat kapitel agnas at de relativt ovanliga men livshotande hud och mjukdelsinfektionerna som kräver snabb kirurgisk intervention och bra samarbete mellan kirurger, intensivvårdsläkare och infektionsläkare. Svampsepsis har okat på IVA pga alltmer avancerad intensivvård och agnas ett eget kapitel da svampsepsis ofta ar svårdiagnosticerat. Empirisk behandling med nya antimykotika har därför blivit allt vanligare och det ar viktigt att ha kännedom om vilka preparat som har bast effekt och ar kostnadseffektiva. Samhällsförvärvade och sjukhusförvärvade intensivvårdskrävande pneumonier har båda hög dödlighet och en sammanfattning av behandlingsalgoritmer ar inkluderade i boken. Intensivvård innebar risk for sjukhusförvärvade infektioner och riktlinjer for hur man skall undvika, diagnosticera och behandla blodkateterassocierade infektioner agnas ett kapitel. For en optimal handläggning av septiska infektioner ar det viktigt att ta reda på förekomst av immunsuppression och komorbiditet, göra en korrekt bedömning av svårighetsgrad, stalla ratt preliminär diagnos inklusive infektionsfokus, sannolik etiologi och risk for antibiotikaresistens. Boken innehåller flera sammanfattningar och checklistor for snabb korrekt empirisk antimikrobiell behandling av intensivvårdskrävande infektioner både på akuten och IVA.

    Vi hoppas att boken skall bidra till att förbättra varden av patienter med sepsis och andra svara infektioner. Stort tack till alla medförfattare som bidragit med sin expertis och till Region Östergötland som bidragit ekonomiskt och möjliggjort utgivning av denna bok.

    Linköping i Januari 2017

    Hakan Hanberger

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  • 20.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Sepsis på akuten & IVA: diagnostik och antibiotikaterapi2013Collection (editor) (Other academic)
    Abstract [sv]

    Sepsis på akuten och IVA baseras på SK-kursen med samma namn. Vi har i andra upplagan flera nya kapitel och hoppas att boken skall bidra till att förbättra vården av patienter med sepsis och andra svåra infektioner.

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  • 21.
    Hedenstierna, M
    et al.
    Karolinska Universitetssjukhuset Huddinge, Stockholm.
    Weiland, O
    Karolinska Universitetssjukhuset Huddinge, Stockholm.
    Brass, A
    Karolinska Institutet, Stockholm .
    Bankwitz, D
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Behrendt, P
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Uhnoo, I
    Akademiska Universitetssjukhuset, Uppsala .
    Aleman, S
    Karolinska Universitetssjukhuset Huddinge och Solna, Stockholm.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Norkrans, G
    Sahlgrenska Universitetssjukhuset, Göteborg .
    Eilard, A
    Sahlgrenska Universitetssjukhuset, Göteborg .
    Glaumann, H
    Karolinska Universitetssjukhuset Huddinge .
    Pietschmann, T
    Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    Sällberg, M
    Karolinska Institutet, Stockholm .
    Brenndörfer, E D
    Karolinska Institutet, Stockholm.
    Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.2015In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 41, no 6, p. 532-543Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.

    AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR.

    METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.

    RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.

    CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

  • 22.
    Henningsson, Anna
    et al.
    Regional Jonköping County, Sweden.
    Lindqvist, Richard
    Umeå University, Sweden.
    Norberg, Peter
    University of Gothenburg, Sweden.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Roth, Anette
    University of Gothenburg, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergstrom, Tomas
    University of Gothenburg, Sweden.
    Overby, Anna K.
    Umeå University, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Human Tick-Borne Encephalitis and Characterization of Virus from Biting Tick2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 8, p. 1485-1487Article in journal (Refereed)
    Abstract [en]

    We report a case of human tick-borne encephalitis (TBE) in which the TBE virus was isolated from the biting tick. Viral growth and sequence were characterized and compared with those of a reference strain. Virus isolation from ticks from patients with TBE may offer a new approach for studies of epidemiology and pathogenicity.

  • 23.
    Henningsson, Anna
    et al.
    Ryhov County Hospital, Jönköping.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gyllemark, Paula
    Ryhov County Hospital, Jönköping.
    Kozak Ljunggren, Monika
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Matussek, Andreas
    Ryhov County Hospital, Jönköping.
    Nyman, Dag
    Ryhov County Hospital, Jönköping.
    Ekerfelt, Christina
    Bimelix Biomedical Laboratory, Mariehamn, Åland, Finland .
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping.
    Forsberg, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Low risk of seroconversion or clinical disease in humans after a bite by an Anaplasma phagocytophilum-infected tick2015In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 6, no 6, p. 787-792Article in journal (Refereed)
    Abstract [en]

    The risk of contracting human granulocytic anaplasmosis (HGA) after a tick bite is mainly unknown. In this study we investigated the clinical and serological response in 30 humans bitten by ticks positive for Anaplasma phagocytophilum (Group A), 30 humans bitten by Borrelia burgdorferi sensu lato (s.l.)-positive ticks (Group B), and 30 humans bitten by ticks negative for both A. phagocytophilum and B. burgdorferi s.l. (Group C). Ticks, blood samples and questionnaires were collected from tick-bitten humans at 34 primary healthcare centres in Sweden and in the Åland Islands, Finland, at the time of the tick bite and after three months. A total of 2553 ticks detached from humans in 2007-2009 were analyzed by polymerase chain reaction, and 31 (1.2%) were positive for A. phagocytophilum, 556 (21.8%) were positive for B. burgdorferi s.l., and eight (0.3%) were co-infected by A. phagocytophilum and B. burgdorferi s.l. The overall prevalence of Anaplasma IgG antibodies in the included participants (n=90) was 17%, and there was no significant difference between the groups A-C. Only one of the participants (in Group C) showed a four-fold increase of IgG antibodies against A. phagocytophilum at the three-month follow-up, but reported no symptoms. The frequency of reported symptoms did not differ between groups A-C, and was unrelated to the findings of A. phagocytophilum and B. burgdorferi s.l. in the detached ticks. We conclude that the risk for HGA or asymptomatic seroconversion after a tick bite in Sweden or in the Åland Islands is low, even if the tick is infected by A. phagocytophilum.

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  • 24.
    Holmbom, Martin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Giske, Christian G.
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden..
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoffmann, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    14-Year Survey in a Swedish County Reveals a Pronounced Increase in Bloodstream Infections (BSI). Comorbidity: An Independent Risk Factor for Both BSI and Mortality2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 11Article in journal (Refereed)
    Abstract [en]

    Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county.

    Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI).

    Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04).

    Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics.

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  • 25.
    Hällgren, Anita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Borgström, S.
    Department of Anaesthesia and Intensive Care, Kalmar County Hospital, Kalmar, Sweden.
    Kullberg, F.
    Department of Anaesthesia and Intensive Care , Central Hospital , Växjö Sweden.
    Wimmerstedt, A.
    Department of Infectious Diseases, Central Hospital, Växjö, Sweden.
    Oscarsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Nordlund, P.
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jönköping Sweden.
    Lindholm, M-L.
    Department of Anaesthesia and Intensive Care, Kalmar County Hospital, Kalmar, Sweden.
    Bonnedahl, J.
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Brudin, L.
    Department of Clinical Physiology, Kalmar County Hospital, Kalmar Sweden.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    High target attainment for β-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 3, p. 11p. 553-563Article in journal (Refereed)
    Abstract [en]

    Patients in the intensive care unit (ICU) are at risk for suboptimal levels of β-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum β-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT). MIC was used as the target and, when available, the actual MIC (MIC) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m. The rate of patients reaching 100% fT greater than MIC was higher (89%, 31/35) compared to the same patients using MIC (60%, p = 0.002). In total, 55% (61/111) reached 100% fT greater than MIC. Increased renal clearance was independently associated to not reaching 100% fT greater than MIC. On repeated sampling, greater than77% of patients had stable serum drug levels around the MIC. Serum concentrations of β-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies. [ABSTRACT FROM AUTHOR]

  • 26.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Sahin, Christofer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Pestoff, Rebecka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Edsjö, Anders
    Sahlgrenska University Hospital Göteborg .
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-5, article id 140616Article in journal (Refereed)
    Abstract [en]

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

  • 27.
    Johansson, Marcus
    et al.
    Kalmar County Hospital, Sweden.
    Manfredsson, Lena
    Kalmar County Hospital, Sweden.
    Wistedt, Annika
    Kalmar County Hospital, Sweden.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Tjernberg, Ivar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Council, Sweden.
    Significant variations in the seroprevalence of C6 ELISA antibodies in a highly endemic area for Lyme borreliosis: evaluation of age, sex and seasonal differences2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 5, p. 476-481Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to assess the seroprevalence of C6 ELISA antibodies in healthy blood donors in Kalmar County, Sweden, in relation to age, sex and time of year (peak season vs off season). In addition, we wanted to assess serological status over time in a group of C6 ELISA seropositive blood donors. Sera were collected from 273 (131 women, 142 men) blood donors in autumn 2011 and 300 (144 women, 156 men) in winter 2014. All sera were analysed in the C6 ELISA and the results were interpreted according to the manufacturers instructions. The seroprevalence was 22% (females 16%, males 28%) in 2011 and 24% (females 15%, males 33%) in 2014. The seroprevalence was significantly higher in males and increased with age. The highest seroprevalence was observed among elderly men, 60-70 years old (46% in 2011 and 52% in 2014). No significant difference was detected in seropositivity between the samples collected in winter and autumn. All (34/34) seropositive blood donors followed over time remained seropositive at follow-up after 22-29 months. C6 ELISA seroprevalence in healthy blood donors is high in Kalmar County, thereby reducing the specificity of a positive test result regarding the clinical diagnosis of Lyme borreliosis (LB). Although C6 seroprevalence appears not to be affected by seasonal sample time, it varies greatly with age and sex. A careful evaluation of pre-test probability is therefore of the utmost importance in the clinical diagnosis of LB, especially in elderly men. We suggest that colleagues in other endemic regions also consider initiating similar evaluations to optimize the laboratory and clinical diagnosis of LB in relation to age and sex.

  • 28.
    Le, Ngai Kien
    et al.
    Natl Hosp Pediat, Hanoi, Vietnam.
    Wertheim, HF
    Univ Oxford, Clin Res Unit, Hanoi, Vietnam; Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford, England; Radboudumc, RCI, Dept Med Microbiol, Nijmegen, Netherlands.
    Vu, Phu Dinh
    Natl Hosp Trop Dis, Hanoi, Vietnam.
    Khu, Dung Thi Khanh
    Natl Hosp Pediat, Hanoi, Vietnam.
    Le, Hai Tanh
    Natl Hosp Pediat, Hanoi, Vietnam.
    Hoang, Bich Thi Ngoc
    Natl Hosp Pediat, Hanoi, Vietnam.
    Vo, Vu Thanh
    HCMC, Childrens Hosp 1, Hanoi, Vietnam.
    Lam, YM
    HCMC, Hosp Trop Dis, Hanoi, Vietnam.
    Vu, DTV
    Univ Oxford, Clin Res Unit, Hanoi, Vietnam; Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford OX1 2JD, England.
    Nguyen, TH
    Natl Hosp Pediat, Hanoi, Vietnam.
    Thai, TQ
    HCMC, Childrens Hosp 1, Hanoi, Vietnam.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Van Nguyen, K
    HCMC, Hosp Trop Dis, Hanoi, Vietnam.
    Nadjm, Behzad
    Univ Oxford, Clin Res Unit, Hanoi, Vietnam; Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford OX1 2JD, England.
    Clarkson, Louise
    Karolinska Inst, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Larsson, Mattias
    University of Oxford, Vietnam; University of Oxford, England; Karolinska Institute, Sweden.
    High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs A multi-centre point prevalence survey2016In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 95, no 27, article id e4099Article in journal (Refereed)
    Abstract [en]

    There is scarce information regarding hospital-acquired infections (HAIs) among children in resource-constrained settings. This study aims to measure prevalence of HAIs in Vietnamese pediatric hospitals. Monthly point prevalence surveys (PPSs) in 6 pediatric intensive care units (ICUs) in 3 referral hospitals during 1 year. A total of 1363 cases (1143 children) were surveyed, 59.9% male, average age 11 months. Admission sources were: other hospital 49.3%, current hospital 36.5%, and community 15.3%. Reasons for admission were: infectious disease (66%), noninfectious (20.8%), and surgery/trauma (11.3%). Intubation rate was 47.8%, central venous catheter 29.4%, peripheral venous catheter 86.2%, urinary catheter 14.6%, and hemodialysis/filtration 1.7%. HAI was diagnosed in 33.1% of the cases: pneumonia (52.2%), septicemia (26.4%), surgical site infection (2%), and necrotizing enterocolitis (2%). Significant risk factors for HAI included age under 7 months, intubation and infection at admission. Microbiological findings were reported in 212 cases (43%) with 276 isolates: 50 Klebsiella pneumoniae, 46 Pseudomonas aeruginosa, and 39 Acinetobacter baumannii, with carbapenem resistance detected in 55%, 71%, and 65%, respectively. Staphylococcus aureus was cultured in 18 cases, with 81% methicillin-resistant Staphylococcus aureus. Most children (87.6%) received antibiotics, with an average of 1.6 antibiotics per case. Colistin was administered to 96 patients, 93% with HAI and 49% with culture confirmed carbapenem resistance. The high prevalence of HAI with carbapenem resistant gram-negative strains and common treatment with broad-spectrum antibiotics and colistin suggests that interventions are needed to prevent HAI and to optimize antibiotic use.

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  • 29.
    Liew-Littorin, C.
    et al.
    Orebro Univ Hosp, Sweden.
    Bruggemann, H.
    Aarhus Univ, Denmark.
    Davidsson, S.
    Orebro Univ, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Hellmark, B.
    Orebro Univ Hosp, Sweden.
    Soderquist, B.
    Orebro Univ Hosp, Sweden; Orebro Univ, Sweden.
    Clonal diversity of Cutibacterium acnes (formerly Propionibacterium acnes) in prosthetic joint infections2019In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 59, p. 54-60Article in journal (Refereed)
    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. (C) 2019 The Authors. Published by Elsevier Ltd.

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  • 30.
    Lindblom, Anders
    et al.
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Wallmenius, Katarina
    Uppsala University, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Nilsson, Kenneth
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Aland Island2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166653Article in journal (Refereed)
    Abstract [en]

    Tick-transmitted diseases are an emerging health problem, and the hard tick Ixodes ricinus is the main vector for Borrelia spp., tick-borne encephalitis virus and most of the spotted fever Rickettsiae in Europe. The aim of the present study was to examine the incidence of rickettsial infection in the southernmost and south central parts of Sweden and the Aland Islands in Finland the risk of infection in humans and its correlation with a bite of a Rickettsia-infected tick, the self-reported symptoms of rickettsial disease, and the prevalence of co-infection between Rickettsia spp. and Borrelia spp. Persons with a recent tick bite were enrolled through public media and asked to answer a questionnaire, provide a blood sample and bring detached ticks at enlistment and at follow-up three months later. Blood samples were previously analysed for Borrelia spp. antibodies and, for this report, analysed for antibodies to Rickettsia spp. by immunofluorescence and in 16 cases also using Western Blot. Ninety-six (44.0%) of the 218 participants were seropositive for IgG antibodies to Rickettsia spp. Forty (18.3%) of the seropositive participants had increased titres at the follow-up, indicating recent/current infection, while four (1.8%) had titres indicating probable recent/current infection (amp;gt;= 1: 256). Of 472 ticks, 39 (8.3%) were Rickettsia sp. positive. Five (31.3%) of 16 participants bitten by a Rickettsia-infected tick seroconverted. Experience of the selfreported symptoms nausea (p = 0.006) and radiating pain (p = 0.041) was more common among those with recent, current or probable infection compared to those who did not seroconvert. Participants who showed seroreactivity or seroconversion to Rickettsia spp. had more symptoms than those who were seronegative. Seven (3.2%) participants showed seroconversion to Borrelia spp., and three (1.4%) of these showed seroconversion to both Rickettsia spp. and Borrelia spp., in accordance with previous studies in Sweden. Symptoms of rickettsial disease were in most of the cases vague and general that were difficult to differentiate from other tick-borne diseases.

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  • 31.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Health and Developmental Care, Department of Infection Control.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Health and Developmental Care, Department of Infection Control.
    Swanberg, J.
    Ryhov Hospital, Sweden.
    Skov, R.
    Statens Serum Institute, Denmark.
    Larsen, A. R.
    Statens Serum Institute, Denmark.
    Larsen, J.
    Statens Serum Institute, Denmark.
    Petersen, A.
    Statens Serum Institute, Denmark.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region2015In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, no 7, p. 1415-1422Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergotland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergotland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clones persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83 % (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68 % (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergotland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.

  • 32.
    Littorin, C
    et al.
    Örebro University, Örebro, Sweden.
    Hellmark, B
    Örebro University Hospital, Örebro, Sweden; Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Söderquist, Bo
    Örebro University Hospital, Örebro, Sweden.
    In vitro activity of tedizolid and linezolid against Staphylococcus epidermidis isolated from prosthetic joint infections.2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 9, p. 1549-1552Article in journal (Refereed)
    Abstract [en]

    Prosthetic joint infections (PJIs) are rare but long-lasting and are serious complications without any spontaneous resolution, requiring additional surgery and long-term treatment with antibiotics. Staphylococci are the most important aetiological agents of PJIs, and among the coagulase-negative staphylococci Staphylococcus epidermidis is the most common. However, S. epidermidis often displays multidrug resistance (MDR), demanding additional treatment options. The objective was to examine the effectiveness of tedizolid and linezolid against S. epidermidis isolated from PJIs. The standard antibiotic susceptibility pattern of S. epidermidis (n = 183) obtained from PJIs was determined by disc diffusion test, and MIC was determined by Etest for tedizolid, linezolid, and vancomycin. Tedizolid displayed MIC values ranging from 0.094 to 0.5 mg/L (MIC50: 0.19 mg/L, MIC90: 0.38 mg/L), linezolid MIC values ranging from 0.25 to 2 mg/L (MIC50: 0.75 mg/L, MIC90: 1 mg/L), and vancomycin MIC values ranging from 0.5 to 3 mg/L (MIC50 and MIC90 both 2 mg/L). According to the disc diffusion test, 153/183 (84%) isolates were resistant to ≥3 antibiotic groups, indicating MDR. In conclusion, S. epidermidis isolates from PJIs were fully susceptible, and the MIC50 and MIC90 values for tedizolid were two- to four-fold dilution steps lower compared with linezolid. Tedizolid is not approved, and there are no reports of long-term treatment, but it may display better tolerability and fewer adverse effects than linezolid; it thus could be a possible treatment option for PJIs, alone or in combination with rifampicin.

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  • 33.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Linköping.
    Palm, Eleonor
    Orebro Univ, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Davies, Julia
    Malmo Univ, Sweden.
    Svensater, Gunnel
    Malmo Univ, Sweden.
    Lönn, Johanna
    Orebro Univ, Sweden; Malmo Univ, Sweden; PEAS Research Institute, Sweden.
    Modified lipoproteins in periodontitis: a link to cardiovascular disease?2019In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 39, no 3, article id BSR20181665Article in journal (Refereed)
    Abstract [en]

    There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

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  • 34.
    Mansson, Emeli
    et al.
    Orebro Univ, Sweden; Univ Orebro, Sweden; Region Vastmanland Uppsala Univ, Sweden.
    Soederquist, Bo
    Orebro Univ, Sweden; Univ Orebro, Sweden; Orebro Univ, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Saerndahl, Eva
    Orebro Univ, Sweden; Univ Orebro, Sweden.
    Demirel, Isak
    Orebro Univ, Sweden; Univ Orebro, Sweden.
    Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1 release from human neutrophils than isolates from normal flora2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 678-684Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to test the hypothesis that Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) differs from S.epidermidis isolated from normal flora in terms of its capacity to induce activation of caspase-1 and release of IL-1 in human neutrophils. The amount of active caspase-1 was determined over 6h by detecting Ac-YVAD-AMC fluorescence in human neutrophils incubated with S.epidermidis isolates from PJIs (ST2) or normal flora. The amount of IL-1 was detected by ELISA in neutrophil supernatants after 6h of incubation. Mean IL-1 release was lower after incubation with S.epidermidis from PJIs compared to isolates from normal flora, but no statistically significant difference was found in active caspase-1. Substantial inter-individual differences in both active caspase-1 and IL-1 were noted. These results suggest that evasion of innate immune response, measured as reduced capacity to induce release of IL-1 from human neutrophils, might be involved in the predominance of ST2 in S.epidermidis PJIs, but that other microbe-related factors are probably also important.

  • 35.
    Molstad, Sigvard
    et al.
    Lund University, Sweden.
    Lofmark, Sonja
    Public Health Agency Sweden, Sweden.
    Carlin, Karin
    Public Health Agency Sweden, Sweden.
    Erntell, Mats
    County Halland, Sweden.
    Aspevall, Olov
    Public Health Agency Sweden, Sweden.
    Blad, Lars
    County Varmland, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hedin, Katarina
    Lund University, Sweden.
    Hellman, Jenny
    Public Health Agency Sweden, Sweden.
    Norman, Christer
    Public Health Agency Sweden, Sweden.
    Skoog, Gunilla
    Public Health Agency Sweden, Sweden.
    Stalsby-Lundborg, Cecilia
    Department Public Heatlh, Sweden.
    Tegmark Wisell, Karin
    Public Health Agency Sweden, Sweden.
    Ahren, Christina
    Sahlgrens Acad, Sweden.
    Cars, Otto
    Public Health Agency Sweden, Sweden.
    Lessons learnt during 20 years of the Swedish strategic programme against antibiotic resistance2017In: Bulletin of the World Health Organization, ISSN 0042-9686, E-ISSN 1564-0604, Vol. 95, no 11, p. 764-773Article in journal (Refereed)
    Abstract [en]

    Increasing use of antibiotics and rising levels of bacterial resistance to antibiotics are a challenge to global health and development. Successful initiatives for containing the problem need to be communicated and disseminated. In Sweden, a rapid spread of resistant pneumococci in the southern part of the country triggered the formation of the Swedish strategic programme against antibiotic resistance, also known as Strama, in 1995. The creation of the programme was an important starting point for long-term coordinated efforts to tackle antibiotic resistance in the country. This paper describes the main strategies of the programme: committed work at the local and national levels; monitoring of antibiotic use for informed decision-making; a national target for antibiotic prescriptions; surveillance of antibiotic resistance for local, national and global action; tracking resistance trends; infection control to limit spread of resistance; and communication to raise awareness for action and behavioural change. A key element for achieving long-term changes has been the bottom-up approach, including working closely with prescribers at the local level. The work described here and the lessons learnt could inform countries implementing their own national action plans against antibiotic resistance.

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  • 36.
    Månsson, Emeli
    et al.
    School of Medical Science, Inflammatory Response and Infection Susceptibility Centre, Uppsala University, Hospital of Västmanland, Västerås, Sweden.
    Sahdo, Berolla
    Inflammatory Response and Infection Susceptibility Centre, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Särndahl, Eva
    School of Medical Sciences, iRiSC - Inflammatory Response and Infection Susceptibility Centre, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    School of Medical Sciences, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lower activation of caspase-1 by Staphylococcus epidermidis isolated from prosthetic joint infections compared to commensals.2018In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 10-14Article in journal (Refereed)
    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.

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  • 37.
    Nakka, Sravya Sowdamini
    et al.
    PEAS Institut AB, Linköping, Sweden, Örebro University, Örebro, Sweden.
    Lönn, Johanna
    PEAS Institut AB, Linköping, Sweden, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Region Östergötland, Public Dental Health Care. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Örebro University, Örebro, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Antibodies produced in vitro in the detection of periodontal bacteria by using surface plasmon resonance analysis2015In: Clinical and Experimental Dental Research, E-ISSN 2057-4347Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated withperiodontitis. This study aims to develop antibodies to P. gingivalis in vitro for real-time detection of bacteria in clinical samples. Lymphocytes were isolated from wholeblood of patient treated for periodontitis and were stimulated with P. gingivalis ATCC33277. B-cell maturation to long-living antibody secreting-plasma cells was studiedusing flow cytometry and immunofluorescence staining. The antibodies developedin vitro were immobilized onto a CM-5 sensor chip of a biosensor to detect the pres-ence of P. gingivalis in the gingival crevicular fluid of patients with periodontitis com-pared to periodontally healthy controls (n = 30). Surface plasmon resonance (SPR)analysis was performed to evaluate specific interactions of bacteria in samples withthe immobilized antibodies. The results of SPR analysis were compared to the detec-tion of P. gingivalis in the samples using DNA–DNA checkerboard hybridizationtechnique. A clear and distinct change in lymphocyte morphology upon stimulationwith P. gingivalis was observed. Anti-P. gingivalis antibodies secreted by CD38+plasma cells showed the presence of all the four IgG subclasses. The results ofDNA–DNA checkerboard analysis were in agreement with that of SPR analysis forthe detection of P. gingivalis in patient samples. Furthermore, incubation with anti-P. gingivalis attenuated the bacterial response in SPR. The in vitro method for antibodyproduction developed during this study could be used for an efficient real-time detec-tion of periodontitis, and the attenuating effects of in vitro antibodies suggest their rolein passive immunization to prevent periodontitis and their associated risk factors.

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  • 38.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Occlusive bandaging of wounds with decreased circulation promotes growth of anaerobic bacteria and necrosis: case report2016In: BMC Research Notes, E-ISSN 1756-0500, Vol. 9, no 394Article in journal (Refereed)
    Abstract [en]

    Background: Topical occlusive/semi-occlusive dressings that induce a damp and trapped environment are widely used in wound treatment. Subjecting the wound with impaired circulation to such trapped/air-free environment potentiates the growth of anaerobic bacteria and risk for serious infection. Case presentation: We present a case of previously healthy Swedish male that had a muscle contusion after heavy trauma that induced impaired circulation. The application of an occlusive bandage to the post-traumatic wound on the patient resulted in a poly-microbial anaerobic infection and necrosis. These complications were treated successfully with antibiotics and open dressing of the wound. Conclusion: The pathophysiology of difficult- to- treat ulcers should be reviewed by the physician and occlusive dressing should be avoided when treating wounds with impaired circulation.

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  • 39.
    Niward, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Towards individualised treatment of tuberculosis2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Each year, around 10 million of individuals develop active tuberculosis (TB). Worldwide, TB is the leading cause of death from an infectious agent surpassing both malaria and HIV. Current treatment regimens are long and therefore encompass a risk of nonadherence and development of acquired drug-resistance, reflected in the increase of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. Indeed, this calls for prudent use of existing TB drugs and improvement of TB treatment strategies. The aim of this thesis was to investigate the current drug susceptibility testing (DST) breakpoints for Mycobacterium tuberculosis (M. tuberculosis), the pharmacokinetics and pharmacodynamics (PK/PD) of TB treatment and to explore the role of therapeutic drug monitoring (TDM) for optimising TB treatment.

    Drug resistance in M. tuberculosis is expressed over a continuous scale and for some drugs it may be identified as low- and high-level resistance. This has been poorly reflected in currently used binary susceptibility breakpoints for TB drugs. Results from genome sequencing and phenotypic DST of ofloxacin and levofloxacin were compared in study I and current breakpoints were found to misclassify up to 25% of M. tuberculosis isolates with resistance mutations in gyrA as susceptible to fluoroquinolones. This finding may have implications for the classification of XDR-TB, treatment of MDR-TB and the evaluation of fluoroquinolones in clinical studies.

    Study II was a prospective cohort study of susceptible TB in Sweden, where drug concentrations of first-line TB drugs were measured along with the susceptibility level of the bacteria defined by the minimum inhibitory concentration (MIC) of M. tuberculosis. First-line drug concentrations below the reference range (16-42%) were common and most pronounced for rifampicin (13/31, 42%). An exploratory investigation of PK/PD parameters displayed a wide distribution of ratios between drug exposures and MICs. Rifampicin exhibited higher level of individual fluctuations over time during TB treatment compared with isoniazid. In study III the plasma drug concentrations of rifampicin were compared to the tuberculosis drug activity assay (TDA) and results showed that rifampicin drug levels, but not drug levels of the other first-line drugs, correlated with TDA. Patients with rifampicin drug levels below 8 mg/L had significantly lower median TDA. This finding supports the use of TDA as a potential indicator for low rifampicin exposure in resource-constrained settings without access to drug concentration analysis. The study design in study II has been further developed in study IV, which is a prospective cohort study of MDR-TB in China, where drug exposure will be explored in relation to individual bacterial MIC and measurements of treatment outcome.

    In summary, the work in this thesis emphasises the importance of reliable DST of M. tuberculosis and the need to re-evaluate the currently used breakpoints. Therapeutic drug monitoring (TDM) based on drug concentrations and MICs is a useful tool to avoid suboptimal drug exposure and to individualise TB treatments. Such strategies may improve treatment regimens and avoid further development of resistance.

    List of papers
    1. Susceptibility testing breakpoints for Mycobacterium tuberculosis categorize isolates with resistance mutations in gyrA as susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB.
    Open this publication in new window or tab >>Susceptibility testing breakpoints for Mycobacterium tuberculosis categorize isolates with resistance mutations in gyrA as susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB.
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    2016 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 2, p. 333-338Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: Fluoroquinolones (FQs) are important in the treatment of MDR-TB and in the definition of XDR-TB. Our objective was to investigate how discrepancies in the phenotypic and genotypic methods for antimicrobial susceptibility testing could affect the interpretation of antimicrobial susceptibility test results.

    METHODS: We analysed MICs of ofloxacin and levofloxacin in Middlebrook 7H10 broth (7H10) as well as sequencing of the quinolone resistance-determining region of the gyrA gene and the MTBDRsl assay in 75 resistant isolates, including MDR and XDR strains of Mycobacterium tuberculosis.

    RESULTS: Among 75 resistant isolates, 27 had mutations associated with FQ resistance. Among isolates with resistance mutations in gyrA, 26% (seven of 27) were susceptible to levofloxacin and ofloxacin by phenotypic testing at 1 mg/L and 2 mg/L. The most common mutation was in codon 94 and these isolates had significantly increased MICs of levofloxacin (2-8 mg/L) compared with isolates with mutations in codon 90 (0.25-2 mg/L, P < 0.05). The sensitivity and specificity for the MTBDRsl assay compared with gyrA sequencing were 96% and 98%, respectively.

    CONCLUSION: Current critical concentrations may classify up to 26% of isolates with gyrA mutations as susceptible to FQs due to a close relationship between susceptible and resistant populations. These results should be considered while improving clinical breakpoints for M. tuberculosis and may have an impact on the definition of XDR-TB.

    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-124557 (URN)10.1093/jac/dkv353 (DOI)000372427600008 ()26538509 (PubMedID)
    Note

    Funding agencies: Heart and Lung Foundation; Swedish Society of Antimicrobial Chemotherapy (SSAC); Swedish Medical Association; Marianne and Marcus Wallenberg Foundation

    Available from: 2016-02-03 Created: 2016-02-03 Last updated: 2019-04-24
    2. Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting
    Open this publication in new window or tab >>Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting
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    2018 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 10, p. 2838-2845Article in journal (Refereed) Published
    Abstract [en]

    Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline. The highest plasma concentrations at 2, 4 and 6 h post-dose (C-high) were determined, as well as estimates of C-high/MIC and area under the concentration-time curve (AUC(0-6))/MIC including the corresponding ratios based on calculated free-drug concentrations. This trial was registered at www.clinicaltrials.gov (NCT02042261). Results: After 2 weeks of treatment, the median C-high values for rifampicin, isoniazid, pyrazinamide and ethambutol were 10.0, 5.3, 41.1 and 3.3 mg/L respectively. Lower than recommended drug concentrations were detected in 42% of the patients for rifampicin (amp;lt;8 mg/L), 19% for isoniazid (amp;lt;3 mg/L), 27% for pyrazinamide (amp;lt;35 mg/L) and 16% for ethambutol (amp;lt;2 mg/L). The median Chigh/MIC values for rifampicin, isoniazid, pyrazinamide and ethambutol were 164, 128, 1.3 and 2.5, respectively, whereas the AUC(0-6)/MIC was 636 (range 156-2759) for rifampicin and 351 (range 72-895) for isoniazid. Conclusions: We report low levels of first-line TB drugs in 16%-42% of patients, in particular for rifampicin. There was a wide distribution of the ratios between drug exposures and MICs. The future use of MIC determinations in TDM is dependent on the development of a reference method and clinically validated pharmacokinetic/pharmacodynamic targets.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS, 2018
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-153707 (URN)10.1093/jac/dky268 (DOI)000452914200032 ()30124844 (PubMedID)
    Note

    Funding Agencies|Research Council of Southeast Sweden; Region of Ostergotland; Marianne and Marcus Wallenberg Foundation; Swedish Heart and Lung Foundation; Swedish Research Council; Stockholm County Council [ALF20160331]

    Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-05-02
    3. Plasma Levels of Rifampin Correlate with the Tuberculosis Drug Activity Assay
    Open this publication in new window or tab >>Plasma Levels of Rifampin Correlate with the Tuberculosis Drug Activity Assay
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    2018 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 5, article id e00218-18Article in journal (Refereed) Published
    Abstract [en]

    The plasma tuberculosis drug activity (TDA) assay may be an alternative tool for therapeutic drug monitoring in resource-limited settings. In tuberculosis (TB) patients (n = 30), TDA and plasma levels of first-line drugs were analyzed 2 h post-dose, 2 weeks after treatment initiation. Patients with plasma levels of rifampin lower than 8 mg/liter had a significantly lower median TDA (1.40 versus 1.68, P = 0.0013). TDA may be used to identify TB patients with suboptimal rifampin levels during TB treatment.

    Place, publisher, year, edition, pages
    AMER SOC MICROBIOLOGY, 2018
    Keywords
    pharmacokinetics; Mycobacterium tuberculosis; rifampin; isoniazid
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-147915 (URN)10.1128/AAC.00218-18 (DOI)000431341200022 ()29483112 (PubMedID)
    Note

    Funding Agencies|Research Council of Southeast Sweden (FORSS); Marianne and Marcus Wallenberg Foundation; Swedish Heart and Lung Foundation; Region of Ostergotland, Sweden; Swedish Research Council

    Available from: 2018-05-23 Created: 2018-05-23 Last updated: 2019-05-01
    4. Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study
    Open this publication in new window or tab >>Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study
    Show others...
    2018 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 9, article id e023899Article in journal (Refereed) Published
    Abstract [en]

    Introduction Individualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB. Methods and analysis Adult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960. Ethics and dissemination This study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal. Trial registration number NCT02816931; Pre-results.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2018
    Keywords
    tuberculosis; clinical pharmacology; public health; microbiology
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-153393 (URN)10.1136/bmjopen-2018-023899 (DOI)000450417800153 ()30287613 (PubMedID)2-s2.0-85054436449 (Scopus ID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation [20150508]; Swedish National Research Council [540-2013-8797]; National Research Foundation of China [81361138019]

    Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2023-08-28Bibliographically approved
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  • 40.
    Niward, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Davies Forsman, Lina
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Chryssanthou, Erja
    Karolinska Univ Hosp Solna, Sweden; Karolinska Inst, Sweden.
    Carlström, Oskar
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Alomari, Teba
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Pohanka, Anton
    Karolinska Univ Hosp Huddinge, Sweden.
    Mansjö, Mikael
    Publ Hlth Agcy Sweden, Sweden.
    Jonsson Nordvall, Michaela
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Johansson, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Eliasson, Erik
    Karolinska Univ Hosp Huddinge, Sweden.
    Werngren, Jim
    Publ Hlth Agcy Sweden, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Simonsson, Ulrika S. H.
    Uppsala Univ, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 10, p. 2838-2845Article in journal (Refereed)
    Abstract [en]

    Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline. The highest plasma concentrations at 2, 4 and 6 h post-dose (C-high) were determined, as well as estimates of C-high/MIC and area under the concentration-time curve (AUC(0-6))/MIC including the corresponding ratios based on calculated free-drug concentrations. This trial was registered at www.clinicaltrials.gov (NCT02042261). Results: After 2 weeks of treatment, the median C-high values for rifampicin, isoniazid, pyrazinamide and ethambutol were 10.0, 5.3, 41.1 and 3.3 mg/L respectively. Lower than recommended drug concentrations were detected in 42% of the patients for rifampicin (amp;lt;8 mg/L), 19% for isoniazid (amp;lt;3 mg/L), 27% for pyrazinamide (amp;lt;35 mg/L) and 16% for ethambutol (amp;lt;2 mg/L). The median Chigh/MIC values for rifampicin, isoniazid, pyrazinamide and ethambutol were 164, 128, 1.3 and 2.5, respectively, whereas the AUC(0-6)/MIC was 636 (range 156-2759) for rifampicin and 351 (range 72-895) for isoniazid. Conclusions: We report low levels of first-line TB drugs in 16%-42% of patients, in particular for rifampicin. There was a wide distribution of the ratios between drug exposures and MICs. The future use of MIC determinations in TDM is dependent on the development of a reference method and clinically validated pharmacokinetic/pharmacodynamic targets.

  • 41.
    Niward, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ek Blom, Linnea
    Karolinska Inst, Sweden.
    Davies Forsman, Lina
    Karolinska Inst, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Eliasson, Erik
    Karolinska Univ Hosp Huddinge, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chryssanthou, Erja
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Plasma Levels of Rifampin Correlate with the Tuberculosis Drug Activity Assay2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 5, article id e00218-18Article in journal (Refereed)
    Abstract [en]

    The plasma tuberculosis drug activity (TDA) assay may be an alternative tool for therapeutic drug monitoring in resource-limited settings. In tuberculosis (TB) patients (n = 30), TDA and plasma levels of first-line drugs were analyzed 2 h post-dose, 2 weeks after treatment initiation. Patients with plasma levels of rifampin lower than 8 mg/liter had a significantly lower median TDA (1.40 versus 1.68, P = 0.0013). TDA may be used to identify TB patients with suboptimal rifampin levels during TB treatment.

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  • 42.
    Niward, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ängeby, Kristian
    Karolinska University Hospital, Stockholm, Sweden. The University of the West Indies, Kingston, Jamaica.
    Chryssanthou, Erja
    Karolinska University Hospital, Stockholm, Karolinska Institute, Stockholm, Sweden..
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bruchfeld, Judith
    Karolinska University Hospital, Stockholm, Sweden Department of Medicine, Karolinska Institute, Solna, Sweden.
    Jureen, Pontus
    The Public Health Agency of Sweden, Stockholm, Sweden.
    Giske, Christian G
    Karolinska University Hospital, Stockholm, Karolinska Institute, Stockholm, Sweden.
    Kahlmeter, Gunnar
    Uppsala University, Uppsala, Sweden. Växjö Hospital, Växjö, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Kalmar.
    Susceptibility testing breakpoints for Mycobacterium tuberculosis categorize isolates with resistance mutations in gyrA as susceptible to fluoroquinolones: implications for MDR-TB treatment and the definition of XDR-TB.2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 2, p. 333-338Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Fluoroquinolones (FQs) are important in the treatment of MDR-TB and in the definition of XDR-TB. Our objective was to investigate how discrepancies in the phenotypic and genotypic methods for antimicrobial susceptibility testing could affect the interpretation of antimicrobial susceptibility test results.

    METHODS: We analysed MICs of ofloxacin and levofloxacin in Middlebrook 7H10 broth (7H10) as well as sequencing of the quinolone resistance-determining region of the gyrA gene and the MTBDRsl assay in 75 resistant isolates, including MDR and XDR strains of Mycobacterium tuberculosis.

    RESULTS: Among 75 resistant isolates, 27 had mutations associated with FQ resistance. Among isolates with resistance mutations in gyrA, 26% (seven of 27) were susceptible to levofloxacin and ofloxacin by phenotypic testing at 1 mg/L and 2 mg/L. The most common mutation was in codon 94 and these isolates had significantly increased MICs of levofloxacin (2-8 mg/L) compared with isolates with mutations in codon 90 (0.25-2 mg/L, P < 0.05). The sensitivity and specificity for the MTBDRsl assay compared with gyrA sequencing were 96% and 98%, respectively.

    CONCLUSION: Current critical concentrations may classify up to 26% of isolates with gyrA mutations as susceptible to FQs due to a close relationship between susceptible and resistant populations. These results should be considered while improving clinical breakpoints for M. tuberculosis and may have an impact on the definition of XDR-TB.

  • 43.
    Nordqvist, H.
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Stockholm South Hospital, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mutant prevention concentration of colistin alone and in combination with rifampicin for multidrug-resistant Acinetobacter baumannii2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 11, p. 1845-1850Article in journal (Refereed)
    Abstract [en]

    Colistin-susceptible isolates of Acinetobacter baumannii often contain subpopulations that are resistant to colistin. Monotherapy with colistin can lead to selective growth of these subpopulations and emergence of colistin-resistant strains. Our objectives were to explore the susceptibility pattern of colistin-resistant subpopulations and investigate if combining colistin with a second antibiotic could prevent their selective growth. Four colistin-susceptible clinical isolates of A. baumannii and one reference isolate were used. The mutant prevention concentration (MPC) of colistin, i.e. the concentration required to block growth of all single-step-mutant subpopulations, was determined by plating an inoculum of 10(9) CFU on Mueller Hinton agar (MHA)-plates containing 2-fold dilutions of colistin (0.125-128 mg/L). Susceptibility testing of colistin-resistant subpopulations, obtained in the MPC assay, was performed with Etest. The MPC of colistin, in combination with rifampicin, was determined by plating an inoculum of 10(9) CFU on MHA-plates containing colistin (0.125-128 mg/L) and fixed concentrations of rifampicin (1.1 mg/L or 4.4 mg/L). The colistin-resistant subpopulations demonstrated increased susceptibility to a number of agents compared to their main populations. These subpopulations were even susceptible to agents that normally are inactive against gram-negative bacteria and all had rifampicin MICs of amp;lt; 0.002 mg/L. The combination of colistin and rifampicin completely inhibited the growth of all colistin-resistant subpopulations and significantly lowered the MPC of colistin for A. baumannii. Combining colistin with rifampicin could be a way to prevent selective growth of colistin-resistant subpopulations of A. baumannii and possibly the emergence of colistin-resistant strains.

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  • 44.
    Peters, Lynn
    et al.
    Karolinska Inst, Sweden.
    Olson, Linus
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Khu, Dung T. K.
    Karolinska Inst, Sweden; Vietnam Natl Childrens Hosp, Vietnam.
    Linnros, Sofia
    Karolinska Inst, Sweden.
    Le, Ngai K.
    Karolinska Inst, Sweden; Vietnam Natl Childrens Hosp, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hoang, Ngoc T. B.
    Vietnam Natl Childrens Hosp, Vietnam.
    Tran, Dien M.
    Res Inst Child Hlth, Vietnam; Vietnam Natl Childrens Hosp, Vietnam.
    Larsson, Mattias
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Multiple antibiotic resistance as a risk factor for mortality and prolonged hospital stay: A cohort study among neonatal intensive care patients with hospital-acquired infections caused by gram-negative bacteria in Vietnam2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 5, article id e0215666Article in journal (Refereed)
    Abstract [en]

    Background Antibiotic resistance (ABR) is an increasing burden for global health. The prevalence of ABR in Southeast Asia is among the highest worldwide, especially in relation to hospital acquired infections (HAI) in intensive care units (ICU). However, little is known about morbidity and mortality attributable to ABR in neonates. Aim This study aimed to assess mortality and the length of hospitalization attributable to ABR in gram-negative bacteria (GNB) causing HAI in a Vietnamese neonatal ICU (NICU). Methods We conducted a prospective cohort study (n = 296) in a NICU in Hanoi, Vietnam, from March 2016 to October 2017. Patients isolated with HAI caused by GNB were included. The exposure was resistance to multiple antibiotic classes, the two outcomes were mortality and length of hospital stay (LOS). Data were analysed using two regression models, controlling for confounders and effect modifiers such as co-morbidities, time at risk, severity of illness, sex, age, and birthweight. Results The overall case fatality rate was 44.3% and the 30 days mortality rate after infection was 31.8%. For every additional resistance to an antibiotic class, the odds of a fatal outcome increased by 27% and LOS increased by 2.1 days. These results were statistically significant (p amp;lt; 0.05). Conclusion ABR was identified as a significant risk factor for adverse outcomes in neonates with HAI. These findings are generally in line with previous research in children and adults. However, heterogeneous study designs, the neglect of important confounders and varying definitions of ABR impair the validity, reliability, and comparability of results.

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  • 45.
    Petersson, Christina
    et al.
    Department of Nursing at School of Health and Welfare, Jönköping University and Member of IMPROVE Research Group at the Academy for Improvement of Health and Welfare Jönköping University Sweden.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Academy for Health and Care Futurum Jönköping Sweden.
    Fust, Ramona
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Discovering aspects of health-experiences of a web-based health diary among adults with primary immunodeficiency2018In: Nursing Open, E-ISSN 2054-1058, Vol. 5, no 4, p. 642-648Article in journal (Refereed)
    Abstract [en]

    Advances in technology generate new opportunities to develop e-health tools to help individuals in self-management by assessing symptoms of illness and its relation to treatments. Self-management is central when living with primary immunodeficiency diseases. The aim was to explore the experiences of people living with primary immunodeficiency, who used a pilot version of the web-based health diary.

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  • 46.
    Petersson, Christina
    et al.
    School of Health and Welfare at Jönköping University, Region Jönköping Council, Sweden.
    Fust, Ramona
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hagstedt, Carina
    Region Hospital of Ryhov, Jönköping, Sweden..
    Vågström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Hospital of Ryhov, Jönköping, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    "Experiences of the burden of treatment" - patient-reports of facilitated subcutaneous immunoglobulin treatment in adults with immunodeficiency.2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 23-24, p. 4270-4278Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: To evaluate patient-reported experiences of facilitated subcutaneous immunoglobulin treatment in adults with primary or secondary immunodeficiency.

    BACKGROUND: Decreased levels of circulating antibodies (humoral immunodeficiency) are often associated with higher infection rates which cause problems in daily living, for example symptoms of severe and recurrent bacterial infections that may cause chronic lung diseases. For some diagnoses, treatment with immunoglobulin becomes critical and life-long. The acceptability of administration forms is important to achieve adherence to treatment, and to increase quality of life for these patients.

    DESIGN: Convergent mixed method approach.

    METHODS: A structured telephone interview with nine questions evaluated on a score scale about treatment experience, satisfaction, and ancillary supplies was used, followed by open-ended questions for each item.

    RESULTS: Prohibiting factors were revealed, exemplified by problems due to technical issues and ancillary supply issues. Promoting factors was shown by high a satisfaction when combining treatment with daily life as well as increased wellbeing. Facilitated subcutaneous immunoglobulin treatment led to fewer treatment sessions, with a time-saving aspect also described by high scores in the item concerning longer treatment interval.

    CONCLUSIONS: The opportunity to be given the best possible treatment plan adjusted for each patients' situation is central. Healthcare professionals should discuss the different aspects that can promote and inhibit the outcomes of treatment.

    RELEVANCE TO CLINICAL PRACTICE: The results can help professionals to understand different factors that may impinge on the patients' everyday life when they are forced into a lifelong treatment regimen. This knowledge is also important for nurses who have a responsibility to promote health concerning patients with long-term conditions in general. This article is protected by copyright. All rights reserved.

  • 47.
    Phu, Vu Dinh
    et al.
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Nadjm, Behzad
    Oxford University Clinical Research Unit, Hanoi, Vietnam.
    Duy, Nguyen Hoang Anh
    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Co, Dao Xuan
    Bach Mai Hospital, Hanoi, Vietnam.
    Mai, Nguyen Thi Hoang
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Trinh, Dao Tuyet
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Campbell, James
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
    Khiem, Dong Phu
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Quang, Tran Ngoc
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Loan, Huynh Thi
    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Binh, Ha Son
    Bach Mai Hospital, Hanoi, Vietnam.
    Dinh, Quynh-Dao
    Oxford University Clinical Research Unit, Hanoi, Vietnam.
    Thuy, Duong Bich
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Lan, Huong Nguyen Phu
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Ha, Nguyen Hong
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Bonell, Ana
    Oxford University Clinical Research Unit, Hanoi, Vietnam.
    Larsson, Mattias
    Karolinska Institutet, Stockholm, Sweden.
    Hoan, Hoang Minh
    Bach Mai Hospital, Hanoi, Vietnam.
    Tuan, Ðang Quoc
    Bach Mai Hospital, Hanoi, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Minh, Hoang Nguyen Van
    Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
    Yen, Lam Minh
    Oxford University Clinical Research Unit, Hanoi, Vietnam.
    Van Hao, Nguyen
    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Binh, Nguyen Gia
    Bach Mai Hospital, Hanoi, Vietnam.
    Chau, Nguyen Van Vinh
    Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
    Van Kinh, Nguyen
    National Hospital for Tropical Diseases, Hanoi, Vietnam.
    Thwaites, Guy E
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
    Wertheim, Heiman F
    Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, Netherlands.
    van Doorn, H Rogier
    Oxford University Clinical Research Unit, Hanoi, Vietnam.
    Thwaites, C Louise
    Oxford University Clinical Research Unit, Hanoi, Vietnam; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
    Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology2017In: Journal of intensive care, ISSN 2052-0492, Vol. 5Article in journal (Refereed)
    Abstract [en]

    Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available.

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  • 48.
    Phu, Vu Dinh
    et al.
    Natl Hosp Trop Dis, Intens Care Unit, Hanoi, Vietnam.
    Wertheim, Heiman FL
    Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hanoi, Vietnam; Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England.
    Larsson, Mattias
    Karolinska Institute, Sweden.
    Nadjm, Behzad
    University of Oxford, England.
    Dinh, Quynh-Dao
    Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Le, Tuyet Thi Diem
    Bach Mai Hosp, Intens Care Unit, Hanoi, Vietnam.
    Trinh, Son Hong
    Viet Duc Hosp, Board Directors, Hanoi, Vietnam.
    Pham, Hung Minh
    St Paul Hosp, Pharm, Hanoi, Vietnam.
    Tran, Cang Thanh
    Viet Tiep Hosp, Intens Care, Hai Phong, Vietnam.
    Doan, Hanh Thi Hong
    Vietnam Sweden Uong Bi Hosp, Board Directors, Quang Ninh, Vietnam.
    Tran, Nguyen Thua
    Hue Cent Gen Hosp, Dept Gen Internal Med & Geriatr, Hue, Vietnam.
    Le, Nhan Duc
    Da Nang Hosp, Board Directors, Da Nang, Vietnam.
    Van Huynh, Nhuan
    Binh Dinh Hosp, Infect Dept, Binh Dinh, Vietnam.
    Tran, Thao Phuong
    Khanh Hoa Hosp, Intens Care Unit, Khanh Hoa, Vietnam.
    Tran, Bao Duc
    Dak Lak Hosp, Planning Dept, Dak Lak, Vietnam.
    Nguyen, Son Truong
    Cho Ray Hosp, Board Directors, Ho Chi Minh City, Vietnam.
    Pham, Thao Thi Ngoc
    Cho Ray Hosp, Board Directors, Ho Chi Minh City, Vietnam.
    Dang, Tam Quang
    Can Tho Cent Gen Hosptial, Board Directors, Can Tho, Vietnam.
    Nguyen, Chau Van Vinh
    Hosp Trop Dis, Board Directors, Ho Chi Minh City, Vietnam.
    Lam, Yen Minh
    Hosp Trop Dis, Board Directors, Ho Chi Minh City, Vietnam.
    Thwaites, Guy
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford OX1 2JD, England; Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
    Van Nguyen, Kinh
    Natl Hosp Trop Dis, Board Directors, Hanoi, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 1, article id e0147544Article in journal (Refereed)
    Abstract [en]

    Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08: 00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/ 3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.

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  • 49.
    Ramezani, Amir
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Nägga, Katarina
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Hansson, Oskar
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Lönn, Johanna
    School of Health and Medical Sciences, Örebro University.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Katoozian, Fateme
    PEAS Institut, Linköping .
    Mansouri, Sepahdar
    PEAS Institut, Linköping .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping .
    Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis2015In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 12, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF.

    METHODS: HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20).

    RESULTS: Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4 %, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7 %, respectively.

    DISCUSSION: In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.

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  • 50.
    Ridberg, Sara
    et al.
    Örebro University, Sweden.
    Hellmark, Bengt
    Örebro University, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Söderquist, Bo
    Örebro University, Sweden.
    Cutibacterium acnes (formerly Propionibacterium acnes) isolated from prosthetic joint infections is less susceptible to oxacillin than to benzylpenicillin2019In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 4, no 3, p. 106-110Article in journal (Refereed)
    Abstract [en]

    Introduction: The frequency of prosthetic joint infections (PJIs) due to Cutibacterium acnes (formerly Propionibacterium acnes) is increasing, especially shoulder PJIs. The recommended antibiotic prophylaxis for hip and knee arthroplasties is beta-lactam antibiotics, predominantly cephalosporins. However, for example in Sweden, isoxazolyl-penicillin cloxacillin is used. No specific recommendations for shoulder arthroplasties are available. The aim of the present study was to determine the minimum inhibitory concentration (MIC) values for different antibiotics for C. acnes; and, more specifically, to compare the MIC values for benzylpenicillin and oxacillin.

    Materials and methods: Minimum inhibitory concentration (MIC) values for nine different antibiotic agents were obtained by gradient test (Etest) using strains of C. acnes (n= 57) isolated from PJIs from shoulders (n=31), hips (n=21), and knees (n=5).

    Results: All isolates had low MIC values for most of the tested antibiotic agents, and showed a wild type MIC distribution. The exception was clindamycin with 9% of the isolates displaying decreased susceptibility. The MIC values obtained for benzylpenicillin were significantly lower than the MIC values for isoxazolyl-penicillin (oxacillin).

    Conclusion: These in vitro results indicate that benzylpenicillin might be a more effective prophylactic treatment to prevent shoulder PJIs caused by C. acnes. However, further studies on the subject are needed, and the effectiveness of the prophylactic treatment should be evaluated using randomized controlled studies and/or register-based studies.

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