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  • 1.
    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, ISSN 1932-6203, 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.

  • 2.
    Chabok, Abbas
    et al.
    Uppsala University.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Smedh, Kenneth
    Uppsala University.
    Påhlman, Lars
    Uppsala University.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Lindberg, Christian
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections2010In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    Objective. Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections. Materials and methods. Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)phenotype was confirmed by Etest. Results. Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes. Conclusions. This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

  • 3.
    Claesson, Carina
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Svensson, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Susceptibility of staphylococci and enterococci to antimicrobial agents at different ward levels in four north European countries2007In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 39, no 11-12, p. 1002-1012Article in journal (Refereed)
    Abstract [en]

    A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively.

  • 4.
    Claesson, Carina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Kronvall, Goeran
    Karolinska Institute.
    Walder, Mats
    Malmö University Hospital.
    Sorberg , Mikael
    Karolinska Institute.
    Antimicrobial activity of tigecycline and comparative agents against clinical isolates of staphylococci and enterococci from ICUs and general hospital wards at three Swedish university hospitals2009In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548 , Vol. 41, no 3, p. 171-181Article in journal (Refereed)
    Abstract [en]

    The activities of tigecycline and comparative agents on staphylococci and enterococci isolated from patients at general hospital wards (GHWs) and intensive care units (ICUs) at 3 university hospitals in Sweden were investigated. Oxacillin disc diffusion and minimal inhibitory concentration with E-test were used. The presence of mecA, vanA or vanB genes was determined with PCR. Statistically significant higher incidence of clindamycin, fusidic acid, rifampicin and multidrug-resistant CoNS was found at ICUs compared to GHWs. Resistance rates were low among S. aureus. Tigecycline, linezolid and vancomycin were the only agents with high activity against methicillin-resistant S. aureus and multidrug-resistant CoNS. Resistance rates were low among E. faecalis, except for high-level gentamicin-resistant (HLGR) E. faecalis. E. faecium showed high resistance rates to ampicillin, piperacillin/tazobactam and imipenem. The HLGR rates among E. faecium were lower than the rates for E. faecalis. Tigecycline and linezolid were the only drugs with high activity against all enterococci including vancomycin-resistant enterococci. No statistically significant differences in susceptibility rates were found between the ward levels for S. aureus and enterococcal isolates and no statistically significant differences were found between the hospitals.

  • 5.
    Ekdahl, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Nilsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Svensson, E.
    Division of Clinical Bacteriology, Department of Laboratory Medicine, Sahlgrenska University Hospital, Sweden.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Rapid decrease of free vancomycin in dense staphylococcal cultures2005In: European journal of clinical microbiology and infectious diseases, ISSN 0934-9723, Vol. 24, no 9, p. 596-602Article in journal (Refereed)
    Abstract [en]

    Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min. No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

  • 6.
    Erlandsson, Marcus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Walther, Sten
    Department of Anaesthesiology, Ullevål University Hospital, University of Oslo, Oslo, Norway.
    Giske, Christian G.
    Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    Jonas, Daniel
    Institute of Environmental Medicine and Hospital Epidemiology, University Medical Centre, Freiburg, Germany.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nordlinder, David
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs2008In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, p. 487-494Article in journal (Refereed)
    Abstract [en]

    Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.

  • 7.
    Gustavsson, O.
    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 Diagnostics, Department of Clinical Microbiology. Innlandet Hospital Trust, Norway.
    Johansson, A. V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Monstein, Hans-Jurg
    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, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bredberg, A.
    Innlandet Hospital Trust, Norway; Lund University, Sweden.
    A wide spectrum of fastidious and ampicillin-susceptible bacteria dominate in animal-caused wounds2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 8, p. 1315-1321Article in journal (Refereed)
    Abstract [en]

    The main purpose of this study was to assess the actual occurrence of Gram-negative oxidase-positive bacteria (GNOP) in human wounds caused by animals, mostly cat and dog bites and scratches, and with signs of infection. We report a prospective series of 92 wound samples. Routine culturing was combined with a procedure optimised for fastidious GNOP. All GNOP isolates were identified by 16S rDNA sequencing to the species level. We observed a more prominent role of GNOP, including at least 30 species mostly in the families Flavobacteriaceae, Neisseriaceae and Pasteurellaceae, and less of Staphylococcus aureus and streptococci. The antibiotic susceptibility pattern was investigated, as GNOP are associated with sudden onset of serious infections, making an early decision on antibiotic treatment vital. All GNOP isolates judged to be clinically relevant displayed susceptibility to ampicillin and meropenem, but resistance to oxacillin, clindamycin and gentamicin was frequent. Our findings emphasise the need to cover GNOP as recommended in guidelines, and not only common wound pathogens, when treating an animal-caused wound.

  • 8.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Burman, LG
    Cars, O
    Erlandsson, Marcus
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordlinder, D
    Walther, Sten
    Linköping University, Department of Medicine and Care, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Low antibiotic resistance rates in Staphylococcus aureus, Escherichia coli and Klebsiella spp but not in Enterobacter spp and Pseudomonas aeruginosa: A prospective observational study in 14 Swedish ICUs over a 5-year period2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 7, p. 937-941Article in journal (Refereed)
    Abstract [en]

    Background: Intensive care units (ICUs) are hot zones for emergence and spread of antibiotic resistance because of frequent invasive procedures, antibiotic usage and transmission of bacteria. We report prospective data on antibiotic use and bacterial resistance from 14 academic and non-academic ICUs, participating in the ICU-STRAMA programme 1999-2003. Methods: The quantity of antibiotics delivered to each ICU was calculated as defined daily doses per 1000 occupied bed days (DDD1000). Specimens for culture were taken on clinical indications and only initial isolates were considered. Species-related breakpoints according to the Swedish Reference Group for Antibiotics were used. Antibiotic resistance was defined as the sum of intermediate and resistant strains. Results: Mean antibiotic use increased from 1245 DDD1000 in 1999 to 1510 DDD1000 in 2003 (P = 0.11 for trend). Of Staphylococcus aureus, 0-1.8% were methicillin resistant (MRSA). A presumptive extended spectrum beta-lactamase (ESBL) phenotype was found in <2.4% of Escherichia coli, based on cefotaxime susceptibility, except a peak in 2002 (4.6%). Cefotaxime resistance was found in 2.6-4.9% of Klebsiella spp. Rates of resistance among Enterobacter spp. to cefotaxime (20-33%) and among Pseudomonas aeruginosa to imipenem (22-33%) and ciprofloxacin (5-21%) showed no time trend. Conclusion: MRSA and cefotaxime-resistant E. coli and Klebsiella spp strains were few despite high total antibiotic consumption. This may be the result of a slow introduction of resistant strains into the ICUs, and good infection control. The cause of imipenem and ciprofloxacin resistance in P. aeruginosa could reflect the increased consumption of these agents plus spread of resistant clones. © 2007 The Authors.

  • 9.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Edlund, Charlotta
    Medical Product Agency, Uppsala.
    Furebring, Mia
    Uppsala University.
    Giske, Christian G.
    MTC – Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Melhus, Åsa
    Uppsala University.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Petersson, Johan
    Karolinska Institutet, Stockholm.
    Sjölin, Jan
    Uppsala University.
    Ternhag, Anders
    Swedish Institute for Communicable Disease Control, Solna.
    Werner, Maria
    Södra Älvsborgs Sjukhus, Borås.
    Eliasson, Erik
    Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Rational use of aminoglycosides - Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 3, p. 161-175Article, review/survey (Refereed)
    Abstract [en]

    The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk–benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

  • 10.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Erlandsson, Marcus
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Burman, Lars G.
    Swedish Institute for Infectious Diseases Control, Solna, Sweden.
    Cars, Otto
    Swedish Institute for Infectious Diseases Control, Solna, Sweden.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Lindgren, Sune
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Olsson-Liljequist, Barbro
    Swedish Institute for Infectious Diseases Control, Solna, Sweden.
    Walther, Sten
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    High Antibiotic Susceptibility Among Bacterial Pathogens In Swedish ICUs2004In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 1, p. 24-30Article in journal (Refereed)
    Abstract [en]

    Local infection control measures, antibiotic consumption and patient demographics from 1999-2000 together with bacteriological analyses were investigated in 29 ICUs participating in the ICU-STRAMA programme. The median antibiotic consumption per ICU was 1147 (range 605-2143) daily doses per 1000 occupied bed d (DDD1000). Antibiotics to which >90% of isolates of an organism were susceptible were defined as treatment alternatives (TA90). The mean number of TA90 was low (1-2 per organism) for Enterococcus faecium (vancomycin:VAN), coagulase negative staphylococci (VAN), Pseudomonas aeruginosa (ceftazidime:CTZ, netilmicin: NET) and Stenotrophomonas maltophilia (CTZ, trimethoprim-sulfamethoxazole: TSU), but higher (3-7) for Acinetobacter spp. (imipenem:IMI, NET, TSU), Enterococcus faecalis (ampicillin:AMP, IMI, VAN), Serratia spp. (ciprofloxacin:CIP, IMI, NET), Enterobacter spp. (CIP, IMI, NET, TSU), E. coli (cefuroxime:CXM, cefotaxime/ceftazidime:CTX/CTZ, CIP, IMI, NET, piperacillin-tazobactam:PTZ, TSU), Klebsiella spp. (CTX/CTZ CIP, IMI, NET, PTZ, TSU) and Staphylococcus aureus (clindamycin, fusidic acid, NET, oxacillin, rifampicin, VAN). Of S. aureus isolates 2% were MRSA. Facilities for alcohol hand disinfection at each bed were available in 96% of the ICUs. The numbers of TA90 available were apparently higher than in ICUs in southern Europe and the US, despite a relatively high antibiotic consumption. This may be due to a moderate ecological impact of the used agents and the infection control routines in Swedish ICUs.

  • 11.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Garcia-Rodriguez, J-A
    Gobernado, M
    Goossens, H
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Struelens, MJ
    French and Portuguese ICU Stud,
    French and Portuguese ICU, Study Groups
    Antibiotic suseptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. 1999In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 281, p. 67-71Article in journal (Refereed)
  • 12.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Monnet, Dominique L
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Intensive care unit2005In: Antibiotic policies.: Theory and practice. / [ed] Ian M. Gould and Jos W.M. van der Meer, New York: Springer , 2005, p. 261-279Chapter in book (Other academic)
    Abstract [en]

    For 50 years, antibiotics have been dispensed like sweets. This must not be allowed to continue. This unique book assembles contributions from experts around the world concerned with responsible use of antibiotics and the consequences of overuse. For the first time, it provides up to the minute texts on both the theoretical aspects of antibiotic stewardship and the practical aspects of its implementation, with consideration of the key differences between developed and developing countries. All concerned with teaching, practice and administration of clinical medicine, surgery, pharmacy, public health, clinical pharmacology, microbiology, infectious diseases and clinical therapeutics will find Antibiotic Policies: Theory and Practice essential reading. Antibiotic use and resistance is not just the responsibility of specialists in the field but the responsibility of all doctors, pharmacists, nurses, healthcare administrators, patients and the general public.

  • 13.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Intensivvårdsavdelningen en het zon för antibiotikaresistens.1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, p. 1276-1277Article in journal (Other (popular science, discussion, etc.))
  • 14.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Claesson, B
    Kärnell, A
    Larsson, P
    Rylander, M
    Svensson, E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Sörberg, M
    Sörén, L
    New species-related MIC breakpoints for early detection of development of resistance among Gram-negative bacteria in Swedish intensive care units. 1999In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 44, p. 611-619Article in journal (Refereed)
  • 15.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maller, Rolf
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2+ and albumin on these drugs.1991In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 35, no 9, p. 1710-1716Article in journal (Refereed)
    Abstract [en]

    The pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 were investigated by studying the postantibiotic effect (PAE) and initial killing. The influence of Ca2+ and albumin on these drugs was also evaluated. The PAE was studied by use of bioluminescence assay of bacterial ATP. Daptomycin at clinically achievable concentrations produced a dose-dependent PAE on E. faecalis (0.6 to 6.7 h) and S. aureus (1.0 to 6.3 h). The long PAE of daptomycin was seen simultaneously with a potent dose-dependent initial killing assayed by viable count determination. The initial change in bacterial ATP was not as extensive as the decrease in viability. Vancomycin at corresponding concentrations produced shorter PAEs on E. faecalis (0.5 to 1.0 h) and S. aureus (1.3 to 1.8 h). This coincides with a weak non-dose-dependent initial change in viability and intracellular ATP. The MICs of vancomycin were not influenced by different Ca2+ concentrations or by the addition of albumin to the broth. The MICs of daptomycin for both strains were lowered, and the PAEs were prolonged with increasing concentrations of Ca2+ in the broth. The PAE of daptomycin was Ca2+ dependent to the same extent as the MIC was. In the presence of physiological concentrations of albumin and free Ca2+, the PAEs of daptomycin on both strains were reduced and the MICs were increased in comparison with the results obtained in pure Mueller-Hinton broth with approximately the same free Ca2+ concentration. This decrease in daptomycin activity was considered to be due to the albumin binding of daptomycin. Despite the albumin binding of daptomycin, the PAE produced on E. faecalis and S. aureus in the presence of a physiological free Ca2+ concentration was still over 6 h at clinically achievable concentrations.

  • 16.
    Holmberg, Martin
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Gustafsson, Fredrik
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Hörnsten, Gunnar
    SIK, The Swedish Institute for Food and Biotechnology, Ideon Lund.
    Winquist, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ljung, Lennart
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Bacteria classification based on feature extraction from sensor data1998In: Biotechnology techniques, ISSN 0951-208X, E-ISSN 1573-6784, Vol. 12, no 4, p. 319-324Article in journal (Refereed)
    Abstract [en]

    Data evaluation and classification have been made on measurements by an electronic nose on the headspace of samples of different types of bacteria growing on petri dishes. The chosen groups were: Escherichia coli, Enterococcus sp., Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus saprophytica. An approximation of the response curve by time was made and the parameters in the curve fit were taken as important features of the data set. A classification tree was used to extract the most important features. These features were then used in an artificial neural network for classification. Using the ‘leave-one-out’ method for validating the model, a classification rate of 76% was obtained

  • 17.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Abednazari, Hossein
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ekdahl, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Samuelsson, Annika
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems2001In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 48, no 1, p. 53-62Article in journal (Refereed)
    Abstract [en]

    Three hundred and twenty-two (322) clinical isolates were collected from patients admitted to intensive care units (ICUs) at eight Swedish hospitals between December 1996 and December 1998. Of the isolates, 244 (76%) were Enterococcus faecalis, 74 (23%) were Enterococcus faecium and four (1%) were other Enterococcus spp. MICs of ampicillin, imipenem, meropenem, piperacillin/tazobactam, ciprofloxacin, trovafloxacin, clinafloxacin, gentamicin, streptomycin, vancomycin, teicoplanin, quinupristin/dalfopristin, linezolid and evernimicin were determined by Etest. Susceptible and resistant isolates were defined according to the species-related MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the Swedish Reference Group for Antibiotics (SRGA). Tentative breakpoints were applied for new/experimental antibiotics. Multidrug resistance among enterococci in ICUs is not uncommon in Sweden, particularly among E. faecium, and includes ampicillin resistance and concomitant resistance to fluoroquinolones. Almost 20% of E. faecalis isolates showed high-level resistance to gentamicin and concomitant resistance to fluoroquinolones. Vancomycin-resistant enterococci were only found sporadically. Among the new antimicrobial agents, linezolid and evernimicin showed the best activity against all enterococcal isolates. There was good concordance between the BSAC, NCCLS and SRGA breakpoints in detecting resistance. When applying the SRGA breakpoints for susceptibility, isolates were more frequently interpreted as intermediate. This might indicate earlier detection of emerging resistance using the SRGA breakpoint when the native population is considered susceptible, but with the risk that isolates belonging to the native susceptible population will be incorrectly interpreted as intermediate.

  • 18.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Burman, Lars G
    Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Olsson-Liljeqvist, Barbro
    Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Walther, Sten
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Rectal colonization and frequency of enterococcal cross-transmission among prolonged-stay patients in two Swedish intensive care units2005In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 37, no 8, p. 561-571Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to gain insight into the dynamics of the rectal flora during prolonged ICU stay, with a particular focus on colonization and cross-transmission with resistant pathogens, and to evaluate methods for the rapid isolation of relevant bacteria from rectal swabs. Patients admitted to a general intensive care unit (GICU) or a cardiothoracic ICU (TICU) at the University Hospital of Linköping, Sweden, between 1 November 2001 and January 2002 with a length of stay > 5 d were included (n = 20). Chromogenic UTI agar medium was used for discrimination of different species, and appropriate antibiotics were added to detect resistance. Direct plating was compared to enrichment broth for a subset of specimens. The study showed an early alteration in rectal flora, with a dramatic decrease in Gram-negative rods in favour of Gram-positive bacteria. An ampicillin- and high-level gentamicin resistant clone of Enterococcus faecium was found in 6 of 10 patients in the GICU and 2 of 11 patients in the TICU. Enrichment broth did not enhance the detection of Gram-negative bacteria compared to direct plating on Chromogenic UTI medium, but enrichment broths were needed for optimal detection of resistant Gram-positive bacteria.

  • 19.
    Hällgren, Anita
    et al.
    Department ofMolecularandClinicalMedicine Linköping University.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Molecular detection of aggregation substance, enterococcal surface protein, and cytolysin genes and in vitro adhesion to urinary catheters of Enterococcus faecalis and E. faecium of clinical origin2009In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 299, no 5, p. 323-332Article in journal (Refereed)
    Abstract [en]

    It has been hypothesized that nosocomial enterococci might have virulence factors that enhance their ability to colonise hospitalised patients. The objectives of this study were to investigate the prevalence of genes encoding 3 virulence factors: aggregation substance (asa1), enterococcal surface protein (esp), and 5 genes within the cytolysin operon (cylA, cylB, cylM, cylL(L), cylL(S)) and cytolysin production in 115 enterococcal clinical isolates (21 Enterococcus faecium and 94 E. faecalis). Adhesion to siliconized latex urinary catheters in relation to presence of esp was analysed in a subset of isolates. The isolates were previously characterised by pulsed-field gel electrophoresis (PFGE). esp was the only virulence gene found in E. faecium. It was found in 71% of the 21 E. faecium isolates. asa1, esp, and the cyl operon were found in 79%, 73% and 13% respectively, of the 94 E. faecalis isolates. There was a complete agreement between presence of the cyl operon and phenotypic cytolysin production. Isolates belonging to a cluster of genetically related isolates carried esp and asa1 more often when compared to unique isolates. No difference was found with respect to cyl genes. E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared. In conclusion, E. faecalis isolates with high-level gentamicin resistance (HLGR) belonging to clusters of genetically related isolates widely distributed in Swedish hospitals, were likely to carry both esp and asa1. Adhesion was not affected by esp.   

  • 20.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Claesson, Carina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Frequency of aggregation substance, cytolysin and enterococcal surface protein in vitro adhesion to urinary catheters of E. faecalis and E. faecium of clinical originManuscript (preprint) (Other academic)
    Abstract [sv]

    Enterococcal isolates, 21 E. faecium and 94 E. faecalis, isolated from blood cultures, rectal specimens and various other clinical samples were examined for the presence of the virulence factors hemolysin/cytolysin, aggregation substance (asa1) and enterococcal surface protein (esp). The isolates were previously characterized by pulsed-field gel electrophoresis (PFGE). Adhesion to siliconized latex urinary catheters was analysed in 14 clinical isolates and 3 control strains. Densities of adhering bacteria were determined by a bioluminescence assay of bacterial ATP. The only virulence factor found in E. faecium, esp, was found in 71% of the 21 E. faceium isolates. Cytolysin production, asa1 and esp were found in 13%, 79% and 73%, respectively, of the 94 E. faecalis isolates. Isolates belonging to a cluster of genetically related isolates differed significantly with respect to carriage of esp and asa1 compared to unique isolates, with the virulence factors more commonly found among clustered isolates (p<0.01). No difference was found with respect to cytolysio production (p = 0.76). E. faecalis isolates adhered with higher bacterial densities than E. faecium. E. faecalis isolates within the same PFGE cluster adhered with similar bacterial densities, but there was no association between adhesion and the presence of esp when isolates within the same cluster were compared (p = 0.38 and 0.64).

  • 21.
    Hällgren, Anita
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Saeedi, Baharak
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Genetic relatedness among Enterococcus faecalis with transposon-mediated high-level gentamicin resistance in Swedish intensive care units2003In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 52, no 2, p. 162-167Article in journal (Refereed)
    Abstract [en]

    We studied 45 isolates of Enterococcus faecalis with high-level gentamicin resistance (HLGR), all but one concomitantly resistant to ciprofloxacin, and 25 ciprofloxacin-resistant isolates without HLGR for genetic relatedness using pulsed-field gel electrophoresis (PFGE). E. faecalis were isolated from patients admitted to intensive care units at eight hospitals in southern Sweden from December 1996 through December 1998. Genomic analysis by PFGE resulted in three clusters of genetically related isolates (designated clusters I, II and III) and 23 unique clones. Cluster I was found predominantly in the eastern and central parts of southern Sweden and clusters II and III in south-western Sweden. Among the 45 isolates with HLGR, 69% belonged to cluster I, 20% to cluster II, and 11% had unique PFGE patterns, which suggests that the majority of isolates with HLGR are closely related. Among the 25 ciprofloxacin-resistant isolates without HLGR, 68% had unique PFGE patterns, 12% belonged to cluster I and 20% to cluster III, which suggests the ciprofloxacin-resistant isolates are not related. All isolates with HLGR contained the aac(6)Ie-aph(2)Ia gene, which was carried on a Tn5281-like transposon in all isolates except one. We conclude that HLGR in E. faecalis was mainly due to dissemination of genetically related clones during the time studied, and that HLGR in these isolates was due to the presence of the aac(6)Ie-aph(2)Ia gene.

  • 22.
    Isaksson, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maller, Rolf
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Synergic post-antibiotic effect of amikacin in combination with beta-lactam antibiotics on gram-negative bacteria.1991In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 28, no 1, p. 25-34Article in journal (Refereed)
    Abstract [en]

    The post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains each of Pseudomonas aeruginosa and Serratia marcescens using a bioluminescent assay of bacterial ATP. Two models were used for combining beta-lactam antibiotics and amikacin: in one model the cultures were incubated with 32 mg/L of ceftazidime, 128 mg/L of ceftriaxone or 32 mg/L of piperacillin for 1 h. Different concentrations of amikacin (0.5-64 mg/L) were then added. Incubation of the combinations continued for one more hour. The antibiotics were eliminated by dilution. In the second model tested, one strain of S. marcescens was simultaneously exposed to amikacin and a beta-lactam antibiotic for 2 h. The PAEs produced by the drugs in combination were longer than the sum of the individual effects of the drugs when they were used alone. Results were equally good with both models. A synergic PAE was also found with amikacin concentrations close to the MIC in combination with low concentrations of ceftazidime, ceftriaxone and piperacillin.

  • 23.
    Isaksson, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maller, Rolf
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis.1991In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 27, p. 9-14Article in journal (Refereed)
    Abstract [en]

    The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics.

  • 24.
    Isaksson, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maller, Rolf
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Postantibiotic effect of aminoglycosides on staphylococci.1993In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 32, no 2, p. 215-222Article in journal (Refereed)
    Abstract [en]

    The postantibiotic effects (PAEs) of amikacin, gentamicin, netilmicin and tobramycin on Staphylococcus aureus and S. epidermidis were determined in vitro by a bioluminescence assay of bacterial ATP. Five strains of S. aureus and two strains of S. epidermidis were exposed for 1 h to varying concentrations of these aminoglycosides. Following removal of the antibiotics by dilution, bacterial regrowth was monitored at hourly intervals. The duration of the PAE increased with increasing aminoglycoside concentration. The mean PAEs for the five S. aureus strains ranged from 5-10 h at clinically achievable aminoglycoside concentrations (16-32 mg/L of amikacin and 4-8 mg/L of gentamicin, netilmicin and tobramycin). The results for one of the strains of S. epidermidis were similar to those observed for the S. aureus strains, while the PAEs on the other less susceptible S. epidermidis strain were shorter (0.5-2.5 h). For comparison, two of the S. aureus strains were exposed for 1 and 2 h to a range of concentrations of dicloxacillin (0.25-32 mg/L); this agent induced a much shorter PAE (0-2.3 h). It may be important to take account of the PAE when designing dosing regimens.

  • 25. Kronvall, Göran
    et al.
    Karlsson, Inga
    Walder, Mats
    Sörberg, Mikael
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Epidemiological MIC cut-off values for tigecycline calculated from Etest MIC values using normalized resistance interpretation2006In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 57, no 3, p. 498-505Article in journal (Refereed)
    Abstract [en]

    Objectives: To apply the normalized resistance interpretation (NRI) method to Etest MIC results which have higher precision than conventional log2 dilution MIC tests due to the inclusion of intermediate values. If successful, NRI might provide an objective tool for the definition of epidemiological MIC cut-off values. Methods: MICs of tigecycline and other antimicrobial agents were determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram-negative species or species groups using the Etest. Histograms of MIC values were constructed for each species and NRI calculations were applied to them. An upper MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was used for setting the epidemiological cut-off values. Results: Calculated cut-off values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with earlier reports on the lack of activity of tigecycline against this species. Conclusions: NRI offers an objective method for the analysis of MICs produced using Etests and the determination of epidemiological MIC cut-off values. © The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

  • 26.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wistedt, Annika
    Department of Clinical Microbiology and Infection Control, Kalmar County Hospital, Kalmar, Sweden.
    Swanberg, Jonas
    Clinical Microbiology Laboratory, Ryhov Hospital, Jönköping, Sweden.
    Skov, Robert
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Rhod Larsen, Anders
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Larsen, Jesper
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Petersen, Andreas
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.

    Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.

    Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.

    Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.

  • 27.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Samuelsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county2009In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 41, no 5, p. 324-333Article in journal (Refereed)
    Abstract [en]

    In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

  • 28.
    Maller, Rolf
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Emanuelsson, Britt- Marie
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Amikacin once daily: a new dosing regimen based on drug pharmacokinetics.1990In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 22, no 5, p. 575-579Article in journal (Refereed)
    Abstract [en]

    Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug.

  • 29.
    Maller, Rolf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sörén, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    A study of amikacin given once versus twice daily in serious infections.1988In: Scandinavian Journal of Infectious Diseases. Supplementum, ISSN 0300-8878, E-ISSN 1651-2502, Vol. 22, no 1, p. 75-79Article in journal (Refereed)
    Abstract [en]

    Forty-five mostly elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin 11.0 or 15.0 mg/kg administered in a single daily dose as an intravenous, short-term infusion or with amikacin 7.5 mg/kg administered twice daily in the same way. The results indicate that administration of amikacin 15 mg/kg in a single daily dose should be a practical and safe principle of administration. However elderly patients often have reduced creatinine clearance and should preferably be given a lower dose of 11 mg/kg bw. The risk of nephrotoxicity did not increase, but conclusions on ototoxicity and clinical efficacy cannot be drawn from this limited study. This should be considered as an initial part of a future multicentre trial.

  • 30.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Balkhed Östholm, Åse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Nilsson, MV
    Nilsson, M
    Dornbusch, Kathrine
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX-M genes in Enterobacteriaceae2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 12, p. 1400-1408Article in journal (Refereed)
    Abstract [en]

    Extended-spectrum β-lactamases (ESBLs) are often mediated by bla-SHV, blaTEM and blaCTX-M genes in Enterobacteriaceae and other Gram-negative bacteria. Numerous molecular typing methods, including PCR-based assays, have been developed for their identification. To reduce the number of PCR amplifications needed we have developed a multiplex PCR assay which detects and discriminates between bla-SHV, blaTEM and blaCTX-M PCR amplicons of 747, 445 and 593 bp, respectively. This multiplex PCR assay allowed the identification of bla-SHV, blaTEM and blaCTX-M genes in a series of clinical isolates of Enterobacteriaceae with previously characterised ESBL phenotype. The presence of blaSHV, blaTEM and blaCTX-M genes was confirmed by partial DNA sequence analysis. Apparently, the universal well-established CTX-M primer pair used here to reveal plasmid-encoded blaCTX-M genes would also amplify the chromosomally located K-1 enzyme gene in all Klebsiella oxytoca strains included in the study.

  • 31.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology.
    Molecular identification of blaCTX-M and blaOXY/K1 beta-lactamase genes in Enterobacteriaceae by sequencing of universal M13-sequence tagged PCR-amplicons.2009In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 9, no 1, p. 7-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Plasmid encoded blaCTX-M enzymes represent an important sub-group of class A beta-lactamases causing the ESBL phenotype which is increasingly found in Enterobacteriaceae including Klebsiella spp. Molecular typing of clinical ESBL-isolates has become more and more important for prevention of the dissemination of ESBL-producers among nosocomial environment.

    METHODS: Multiple displacement amplified DNA derived from 20 K. pneumoniae and 34 K. oxytoca clinical isolates with an ESBL-phenotype was used in a universal CTX-M PCR amplification assay. Identification and differentiation of blaCTX-M and blaOXY/K1 sequences was obtained by DNA sequencing of M13-sequence-tagged CTX-M PCR-amplicons using a M13-specific sequencing primer.

    RESULTS: Nine out of 20 K. pneumoniae clinical isolates had a blaCTX-M genotype. Interestingly, we found that the universal degenerated primers also amplified the chromosomally located K1-gene in all 34 K. oxytoca clinical isolates. Molecular identification and differentiation between blaCTX-M and bla OXY/K1-genes could only been achieved by sequencing of the PCR-amplicons. In silico analysis revealed that the universal degenerated CTX-M primer-pair used here might also amplify the chromosomally located blaOXY and K1-genes in Klebsiella spp. and K1-like genes in other Enterobacteriaceae.

    CONCLUSION: The PCR-based molecular typing method described here enables a rapid and reliable molecular identification of blaCTX-M, and blaOXY/K1-genes. The principles used in this study could also be applied to any situation in which antimicrobial resistance genes would need to be sequenced.

  • 32.
    Nilsson, Lennart E
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Frimodt-Moller, Niels
    National Centre for Antimicrobials and Infection Control.
    Vaara, Martti
    Helsinki University Hospital.
    Skov Simonsen, Gunnar
    University Hospital N Norway.
    Comparative activity of tigecycline and tetracycline on Gram-negative and Gram-positive bacteria revealed by a multicentre study in four North European countries2011In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 43, no 9, p. 707-713Article in journal (Refereed)
    Abstract [en]

    Background: This study involves a multicentre surveillance of tigecycline and tetracycline activity against Gram-negative and Gram-positive bacteria from primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs) in Denmark (n = 9), Finland (n = 10), Norway (n = 7) and Sweden (n = 19). Methods: The hospitals were each asked to test 30 consecutive Gram-positive and 30 Gram-negative clinical isolates. Supportive information accompanying each isolate included the study centre, ward level (PCC, GHW, or ICU), patient identification and source of the isolate. Minimum inhibitory concentrations (MICs) for tetracycline and tigecycline were determined with the Etest. Results: The isolates collected comprised 1610 Gram-negative and 1767 Gram-positive clinical isolates. The study showed low rates of non-susceptibility (intermediate (I) and resistant (R)) to tigecycline: andlt; 1% in Escherichia coli, though other Enterobacteriaceae showed higher rates (Enterobacter cloacae (7%), Klebsiella pneumoniae (9%) and Serratia spp. (23%)). The overall non-susceptibility rate for tigecycline in Enterobacteriaceae with species-related breakpoints for tigecycline was 6% (4% excluding Serratia spp.). The activity of tigecycline against Haemophilus influenzae and Acinetobacter spp. was high with a MIC(50) of 0.25 mg/l and MIC(90) of 1 mg/l. The prevalence of non-susceptibility to tigecycline among Gram-positive bacteria was andlt; 1%. The corresponding figure for tetracycline was 14%. The activity of tigecycline against Streptococcus pneumoniae was high with MIC(50) and MIC(90) of 0.125 mg/l. Conclusion: Tigecycline showed good overall in vitro activity against Gram-positive and Gram-negative isolates, including both tetracycline-susceptible and resistant isolates. Most non-susceptibility to tigecycline among Enterobacteriaceae other than E. coli was I (6%), rather than R (andlt; 1%). This indicates a problem setting interpretive species-related tigecycline breakpoints for Enterobacteriaceae other than E. coli.

  • 33.
    Odenholt, I
    et al.
    Department of Infectious Diseases, Uppsala University, Sweden.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Cars, O
    Postantibiotic and bactericidal effect of imipenem against Pseudomonas aeruginosa.1989In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 8, no 2, p. 136-141Article in journal (Refereed)
    Abstract [en]

    The postantibiotic effect of imipenem on Pseudomonas aeruginosa was studied at different inocula using one ATCC strain and four clinical isolates. The postantibiotic effect was measured using two different methods: viable counts and bioluminescence assay of intracellular bacterial ATP. The postantibiotic effect could be demonstrated with both methods (viable counts 1-2 h, ATP assay 3-5 h) for all strains at an inoculum of 10(6) CFU/ml. When the inoculum was raised to 10(8) CFU/ml, no postantibiotic effect could be observed with either method using routine growth conditions. This disappearance of the postantibiotic effect coincided with a loss of bactericidal effect of imipenem when high inocula were used. Improved oxygenation of the cultures restored the bactericidal and postantibiotic effects of imipenem at high inocula.

  • 34.
    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, ISSN 1932-6203, 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.

  • 35.
    Saeedi, Baharak
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Jonasson, Jon
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Genetic relatedness of Enterococcus faecalis isolates with high-level gentamicin resistance from patients with bacteraemia in the south east of Sweden 1994-20012004In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 36, no 6-7, p. 405-409Article in journal (Refereed)
    Abstract [en]

    High-level gentamicin resistant (HLGR) enterococci (Enterococcus faecalis and Enterococcus faecium) have become a substantial nosocomial problem in many countries. In this study, we investigated the prevalence of HLGR enterococci and their genetic relatedness in blood culture isolates from patients with bacteraemia admitted to the 3 hospitals in Östergötland, a county in the south east of Sweden, during 1994–2001. 36 of 250 E. faecalis (14%) and 4 of 106 E. faecium isolates (4%) were shown by PCR to carry the aac(6′)-Ie-aph(2″)-Ia aminoglycoside modifying gene and these isolates were also classified as HLGR enterococci by the gentamicin antibiotic disk diffusion method. A majority of HLGR E. faecalis isolates (83%) belonged to the same cluster of genetically related isolates, according to the pulsed-field gel electrophoresis (PFGE) patterns, whereas all 4 HLGR E. faecium isolates had unique PFGE patterns. In conclusion, our study showed that in contrast to studies from many other countries, the presence of HLGR enterococci was more common in E. faecalis than in E. faecium and appeared the first time in 1996 and 1999, respectively. Bacteraemia with HLGR enterococci in Östergötland was mainly due to the spread of a cluster related of E. faecalis strains.

  • 36.
    Saeedi, Baharak
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Jonasson, Jon
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Modified pulsed-field gel electrophoresis protocol for typing of enterococci2002In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 110, no 12, p. 869-874Article in journal (Refereed)
    Abstract [en]

    Controlling the spread of vancomycin-resistant enterococci (VRE) is an important task in hospital epidemiology. Pulsed-field gel electrophoresis (PFGE) has become the golden standard for molecular epidemiological characterisation of enterococcal isolates. For separation of DNA fragments by PFGE, different electrophoresis conditions have been recommended, but none of these protocols allows a satisfactory separation of both small and large DNA fragments of enterococci simultaneously. In this study we have speeded up the preparation of chromosomal DNA and defined new electrophoresis conditions that enhance separation of small and large DNA fragments for subtyping of enterococci with a 24 h PFGE.

  • 37.
    Saeedi, Baharak
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Hällgren, Anita
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Jonasson, Jon
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Kühn, I.
    Department of Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Phene Plate (PhP) biochemical fingerprinting: a screening method for epidemiological typing of enterococcal isolates?2005In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 113, no 9, p. 603-612Article in journal (Refereed)
    Abstract [en]

    Pulsed-field gel electrophoresis (PFGE) is currently considered the gold standard for genotyping of enterococci. However, PFGE is both expensive and time-consuming. The purpose of this study was to investigate whether the PhP system can be used as a reliable clinical screening method for detection of genetically related isolates of enterococci. If so, it should be possible to minimize the number of isolates subjected to PFGE typing, which would save time and money. Ninety-nine clinical enterococcal isolates were analysed by PhP (similarity levels 0.90–0.975) and PFGE (similarity levels ≤3 and ≤6 bands) and all possible pairs of isolates were cross-classified as matched or mismatched. We found that the probability that a pair of isolates (A and B) belonging to the same type according to PhP also belong to the same cluster according to PFGE, i.e. p(APFGE=BPFGE • APhP=BPhP), and the probability that a pair of isolates of different types according to PhP also belong to different clusters according to PFGE, i.e. p(APFGE≠BPFGE • APhP≠BPhP), was relatively high for E. faecalis (0.86 and 0.96, respectively), but was lower for E. faecium (0.51 and 0.77, respectively). The concordance which shows the probability that PhP and PFGE agree on match or mismatch was 86%–93% for E. faecalis and 54%–66% for E. faecium, which indicates that the PhP method may be useful for epidemiological typing of E. faecalis in the current settings but not for E. faecium.

  • 38.
    Samuelsson, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Chabok, Abbas
    Uppsala University, Sweden .
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Changes in the aerobic faecal flora of patients treated with antibiotics for acute intra-abdominal infection2012In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 44, no 11, p. 820-827Article in journal (Refereed)
    Abstract [en]

    Background: An open observational study was performed to investigate changes in the rectal flora and antibiotic susceptibility among faecal bacteria in patients treated with antibiotics for acute intra-abdominal infection. Methods: One hundred and forty patients with acute intra-abdominal infection requiring antibiotic treatment and hospitalization were included. Eight surgical units from the southern part of Sweden participated, between January 2006 and November 2007. Antibiotic treatments were according to local guidelines. Rectal swabs were obtained on admission (sample 1) and 2-14 days after the end of antibiotic treatment (sample 2). Aerobic bacteria and yeasts were analysed. The material was divided into 2 groups: 1 group with Enterobacteriaceae and 1 group with non-fermentative Gram-negative bacteria. The susceptibility to antibiotics in each group was compared between samples 1 and 2. Results: The main finding of this study on patients with severe intra-abdominal infections was a shift in the aerobic faecal flora following antibiotic treatment, from Escherichia coli to other more resistant Enterobacteriaceae, Enterococcus faecium, and yeasts. The susceptibility to cephalosporins and piperacillin-tazobactam decreased in Enterobacteriaceae. Conclusions: Following antibiotic treatment, a shift in the aerobic rectal flora to species with intrinsic antibiotic resistance was observed. This indicates that the emergence of resistance is not due to new mutations, but rather to selection of more resistant species. This should be taken into account when designing treatments for secondary intra-abdominal infections.

  • 39.
    Sun, Qiang
    et al.
    Shandong University, Peoples R China.
    Dyar, Oliver J.
    North Devon Dist Hospital, England.
    Zhao, Lingbo
    Shandong University, Peoples R China.
    Tomson, Goran
    Karolinska Institute, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Grape, Malin
    Public Health Agency Sweden, Sweden.
    Song, Yanyan
    Shandong University, Peoples R China.
    Yan, Ling
    Jinan Central Hospital, Peoples R China.
    Stalsby Lundborg, Cecilia
    Karolinska Institute, Sweden.
    Overuse of antibiotics for the common cold - attitudes and behaviors among doctors in rural areas of Shandong Province, China2015In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 16, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Irrational antibiotic use is common in rural areas of China, despite the growing recognition of the importance of appropriate prescribing to contain antibiotic resistance. The aim of this study was to analyze doctors attitudes and prescribing practices related to antibiotics in rural areas of Shandong province, focusing on patients with the common cold. Methods: A survey was conducted with doctors working at thirty health facilities (village clinics, township health centers and county general hospitals) in three counties within Shandong province. Questions were included on knowledge and attitudes towards antibiotic prescribing. Separately, a random selection of prescriptions for patients with the common cold was collected from the healthcare institutions at which the doctors worked, to investigate actual prescribing behaviors. Results: A total of 188 doctors completed the survey. Most doctors (83%, 149/180) had attended training on antibiotic use since the beginning of their medical practice as a doctor, irrespective of the academic level of their undergraduate training. Of those that had training, most had attended it within the past three years (97%, 112/116). Very few doctors (2%, 3/187) said they would give antibiotics to a patient with symptoms of a common cold, and the majority (87%, 156/179) would refuse to prescribe an antibiotic even if patients were insistent on getting them. Doctors who had attended training were less likely to give antibiotics in this circumstance (29% vs. 14%, p less than 0.001). A diagnosis of common cold was the only diagnosis reported on 1590 out of 8400 prescriptions. Over half (55%, 869/1590) of them included an antibiotic. Prescriptions from village clinics were more likely to contain an antibiotic than those from other healthcare institutions (71% vs. 44% [township] vs. 47% [ county], p less than 0.001). Conclusions: Most doctors have recently attended training on antibiotic use and report they would not prescribe antibiotics for patients with a common cold, even when placed under pressure by patients. However, more than half of the prescriptions from these healthcare institutions for patients with the common cold included an antibiotic. Exploring and addressing gaps between knowledge and practice is critical to improving antibiotic use in rural China.

  • 40.
    Sun, Qiang
    et al.
    Shandong University, Peoples R China.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Zhao, Lingbo
    Shandong University, Peoples R China.
    Stalsby Lundborg, Cecilia
    Karolinska Institute, Sweden.
    Song, Yanyan
    Shandong University, Peoples R China.
    Grape, Malin
    Public Health Agency Sweden, Sweden.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Tomson, Goran
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Varying High Levels of Faecal Carriage of Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in Rural Villages in Shandong, China: Implications for Global Health2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e113121-Article in journal (Refereed)
    Abstract [en]

    Antibiotic resistance is considered a major threat to global health and is affected by many factors, of which antibiotic use is probably one of the more important. Other factors include hygiene, crowding and travel. The rapid resistance spread in Gram-negative bacteria, in particular extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E), is a global challenge, leading to increased mortality, morbidity and health systems costs worldwide. Knowledge about resistance in commensal flora is limited, including in China. Our aim was to establish the faecal carriage rates of ESBL-E and find its association with known and suspected risk factors in rural residents of all ages in three socio-economically different counties in the Shandong Province, China. Faecal samples and risk-factor information (questionnaire) were collected in 2012. ESBL-E carriage was screened using ChromID ESBL agar. Risk factors were analysed using standard statistical methods. Data from 1000 individuals from three counties and in total 18 villages showed a high and varying level of ESBL-E carriage. Overall, 42% were ESBL-E carriers. At county level the carriage rates were 49%, 45% and 31%, respectively, and when comparing individual villages (n = 18) the rate varied from 22% to 64%. The high level of ESBL-E carriage among rural residents in China is an indication of an exploding global challenge in the years to come as resistance spreads among bacteria and travels around the world with the movement of people and freight. A high carriage rate of ESBL-E increases the risk of infection with multi-resistant bacteria, and thus the need for usage of last resort antibiotics, such as carbapenems and colistin, in the treatment of common infections.

  • 41.
    Sun, Yi-Qian
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection2003In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 8, no 2, p. 149-157Article in journal (Refereed)
    Abstract [en]

    Background. Mongolian gerbils are frequently used to study Helicobacter pylori-induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model.

    Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection.

    Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons.

    Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant.

    Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.

  • 42.
    Svedjeholm, Rolf
    et al.
    Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
    Vanhanen, Ingemar
    Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
    Håkansson, Erik
    Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
    Joachimsson, P. O.
    Department of Anesthesiology, Akademiska Hospital, Uppsala, Sweden.
    Jorfeldt, Lennart
    Department of Thoracic Physiology, Karolinska Hospital, Stockholm.
    Nilsson, Lennart
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Metabolic and hemodynamic effects of intravenous glutamate infusion early after coronary operations1996In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 112, no 6, p. 1468-1477Article in journal (Refereed)
    Abstract [en]

    Amino acids, particularly glutamate, have been proposed to play an important role in the recovery of cardiac oxidative metabolism after ischemia. In this investigation, the metabolic and hemodynamic effects of glutamate infusion after coronary operations were studied. From 220 to 240 ml 0.1 mol/L l-glutamic acid solution was infused in 10 patients during 1 hour starting 2 hours after operation. A control group of 10 patients received an infusion of 240 ml saline solution. During glutamate infusion, there were significant increases in the uptake of glutamate (from 0.7 ± 0.2 μmol/min in the basal state to a peak of 5.7 ± 1.2 μmol/min at 20 minutes) and lactate (from 4.9 ± 2.0 μmol/min in the basal state to 14.1 ± 4.4 μmol/min at 60 minutes; p < 0.01), whereas the uptake and release of other substrates remained essentially unaffected. Arterial glutamate levels (in whole blood) increased from 103 ± 10 μmol/L to 394 ± 20 μmol/L at 60 minutes. Thirty minutes after discontinuation of the glutamate infusion, arterial levels had decreased to 129 ± 17 μmol/L. The markedly improved utilization of lactate and the unchanged release of alanine together suggest that the oxidative metabolism of the heart was stimulated by glutamate. The metabolic changes were associated with improved myocardial performance. Left ventricular stroke work index increased from 26.8 ± 2.1 gm · beat-1· m-2body surface area to 31.3 ± 3.1 gm · beat-1· m-2body surface area during glutamate infusion. Metabolic support with amino acids may provide a means to improve recovery of metabolic and hemodynamic function of the heart early after cardiac operations.

  • 43.
    Svensson, E
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Hanberger, Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson, Maud
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Pharmacodynamic effects of amikacin, ciprofloxacin and imipenem on growing and non-growing Escherichia coli and Pseudomonas aeruginosa. 1999In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 5, p. 140-148Article in journal (Refereed)
  • 44.
    Svensson, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Nilsson, Maud
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Sörberg, M
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori2002In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 46, no 7, p. 2244-2248Article in journal (Refereed)
    Abstract [en]

    Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and tinidazole alone and in combination with clarithromycin were performed by bioluminescence assay of intracellular ATP. The pharmacodynamic parameter control-related effective regrowth time (CERT) was used. CERT is defined as the time required for the resumption of logarithmic growth and a return of the level of growth to the preexposure inoculum in the test culture minus the corresponding time in the control culture. CERT measures the combined effects of the initial level of killing and postantibiotic effect. The incubation times and drug concentrations were chosen according to their half-lives and their clinically achievable concentrations. The study shows that the parameter CERT is useful for the testing of antibiotic combinations. The CERTs induced by clarithromycin, metronidazole, and tinidazole alone and in the combinations tested were concentration dependent, with no maximum response, indicating that the use of high doses may be preferable. The combinations with the highest concentrations induced synergistic effects and prevented regrowth. The use of tinidazole in combination with clarithromycin proved to give the longest CERTs, indicating that this is the most effective combination.

  • 45.
    Svensson, Margareta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ström, Magnus
    Divisions of Clinical Microbiology.
    Nilsson, Maud
    Divisions of Clinical Microbiology.
    Sörberg, Mikael
    Infectious Diseases Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden .
    Erratum: Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori (Antimicrobial Agents and Chemotherapy (2002) 462002In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 46, no 11, p. 3693article id 3693Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 46.
    Tärnberg, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology.
    Monstein, Hans-Jürg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Molecular identification of blaSHV, blaLEN and blaOKP β-lactamase genes in Klebsiella pneumoniae by bi-directional sequencing of universal SP6- and T7-sequence-tagged blaSHV-PCR amplicons2009In: Molecular and Cellular Probes, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 23, no 3-4, p. 195-200Article in journal (Refereed)
    Abstract [en]

    Plasmid encoded blaSHV enzymes represent an important sub-group of class A β-lactamases causing an ESBL-phenotype which is increasingly found in Enterobacteriaceae including Klebsiella pneumoniae. The chromosomally encoded β-lactamase blaLEN and blaOKP enzymes, which so far only have been found in K. pneumoniae, do not hydrolyse extended-spectrum cephalosporins. In the present study, multiple displacement amplified DNA derived from 20 K. pneumoniae clinical isolates with a blaSHV-like genotype was used in a universal SHV PCR assay using SP6- (forward) and T7- (reverse) sequence-tagged primers. Identification and differentiation of blaSHV, blaLEN and blaOKP genes was obtained by bi-directional amplicon sequencing using SP6- and T7-specific primers. Three well characterised K. pneumoniae strains having a SHV-genotype were included in the study. The bi-directional amplicon sequencing, covering 800 bp (93%) of the blaSHV, blaLEN and blaOKP enzyme encoding sequences, allowed for an unequivocal discrimination of SHV, LEN and OKP genes. Moreover, sequencing revealed the presence of blaSHV allelic variants in six K. pneumoniae isolates in which the amplicons had to be cloned accordingly. Based on deduced amino-acid sequences, a dendrogram was constructed. Seventeen out of 20 K. pneumoniae isolates with an ESBL-phenotype formed a SHV-like cluster, two were LEN-like, and one isolate was OKP-like. The PCR-based molecular typing method described here enables a rapid, reliable and cost-effective identification and differentiation of blaSHV, blaOKP and blaLEN genes.

  • 47.
    Tärnberg, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    In vitro activity of beta-lactam antibiotics against CTX-M-producing Escherichia coli2011In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 8, p. 981-987Article in journal (Refereed)
    Abstract [en]

    Beta-lactam antibiotics have been discussed as options for the treatment of infections caused by multiresistant extended-spectrum beta-lactamase (ESBL)-producing bacteria if the minimum inhibitory concentration (MIC) is low. The objective of this study was to investigate the in vitro activity of different beta-lactam antibiotics against CTX-M-producing Escherichia coli. A total of 198 isolates of E. coli with the ESBL phenotype were studied. Polymerase chain reaction (PCR) amplification of CTX-M genes and amplicon sequencing were performed. The MICs for amoxicillin-clavulanic acid, aztreonam, cefepime, cefotaxime, ceftazidime, ceftibuten, ertapenem, imipenem, mecillinam, meropenem, piperacillin-tazobactam, and temocillin were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC(50) and MIC(90) values were calculated. Isolates from CTX-M group 9 showed higher susceptibility to the beta-lactam antibiotics tested than isolates belonging to CTX-M group 1. More than 90% of the isolates belonging to CTX-M group 9 were susceptible to amoxicillin-clavulanic acid, ceftazidime, ceftibuten, piperacillin-tazobactam, and temocillin. The susceptibility was high to mecillinam, being 91%, regardless of the CTX-M group. All isolates were susceptible to imipenem and meropenem, and 99% to ertapenem. This study shows significant differences in susceptibility to different beta-lactam antibiotics among the CTX-M-producing E. coli isolates and a significant difference for many antibiotics tested between the CTX-M-producing groups 1 and 9. The good in vitro activity of other beta-lactam antibiotics compared to carbapenems indicate that clinical studies are warranted in order to examine the potential role of these beta-lactam antibiotics in the treatment of infections caused by multiresistant ESBL-producing E. coli.

  • 48.
    Walther, Sten
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Agvald-Öhman, Christina
    Blomqvist, Hans
    Monnet, Dominique
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Hanberger, Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Multiresistenta bakterier kan bli allt större hot på svenska IVA.2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 49, p. 3930-3933Article in journal (Other academic)
    Abstract [en]

      

  • 49.
    Walther, Sten
    et al.
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Erlandsson, M.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Olsson-Liljequist, B.
    Smittskyddsinstitutet, Solna, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    The Icustrama Study Group (2002),
    Burman, L.G.
    Smittskyddsinstitutet, Solna, Sweden.
    Cars, O.
    Smittskyddsinstitutet, Solna, Sweden.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Hoffman, Mikael
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Kahlmeter, G.
    Department of Clinical Microbiology, Växjö lasarett.
    Lindgren, S.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units2002In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, Vol. 46, no 9, p. 1075-1081Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of this work was to study usage of antibiotics, its possible determinants, and patterns of bacterial resistance in Swedish intensive care units (ICUs).

    Methods: Prospectively collected data on species and antibiotic resistance of clinical isolates and antibiotic consumption specific to each ICU in 1999 were analyzed together with answers to a questionnaire. Antibiotic usage was measured as defined daily doses per 1000 occupied bed days (DDD1000).

    Results: Data were obtained for 38 ICUs providing services to a population of approximately 6 million. The median antibiotic consumption was 1257 DDD1000 (range 584–2415) and correlated with the length of stay but not with the illness severity score or the ICU category. Antibiotic consumption was higher in the ICUs lacking bedside devices for hand disinfection (2193 vs. 1214 DDD1000, p=0.05). In the ICUs with a specialist in infectious diseases responsible for antibiotic treatment the consumption pattern was different only for use of glycopeptides (58% lower usage than in other ICUs: 26 vs. 11 DDD1000,P=0.02). Only 21% of the ICUs had a written guideline on the use of antibiotics, 57% received information on antibiotic usage at least every 3 months and 22% received aggregated resistance data annually. Clinically significant antimicrobial resistance was found among Enterbacter spp. to cephalosporins and among Enterococcus spp. to ampicillin.

    Conclusions: Availability of hand disinfection equipment at each bed and a specialist in infectious diseases responsible for antibiotic treatment were factors that correlated with lower antibiotic consumption in Swedish ICUs, whereas patient-related factors were not associated with antibiotic usage.

  • 50.
    Wertheim, Heiman F. L.
    et al.
    Oxford University Clinical Research Unit, Hanoi, Viet Nam.
    Chandna, Arjun
    Oxford University Clinical Research Unit, Hanoi, Viet Nam.
    Dinh Vu, Phu
    National Hospital for Tropical Diseases, Hanoi, Viet Nam.
    Van Pham, Ca
    National Hospital for Tropical Diseases, Hanoi, Viet Nam.
    Thi Nguyen, Phong Dai
    National Hospital for Tropical Diseases, Hanoi, Viet Nam.
    Minh Lam, Yen
    National Hospital for Tropical Diseases, Hanoi, Viet Nam.
    Van Nguyen, Chau Vinh
    Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
    Larsson, Mattias
    Oxford University Clinical Research Unit, Hanoi, Viet Nam.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Farrar, Jeremy
    University of Oxford, Vietnam South East Asia Infect Disease Clin Research Network, Vietnam.
    Van Nguyen, Kinh
    National Hospital for Tropical Diseases, Hanoi, Viet Nam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Providing Impetus, Tools, and Guidance to Strengthen National Capacity for Antimicrobial Stewardship in Viet Nam2013In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, no 5Article in journal (Other academic)
    Abstract [en]

    n/a

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